Skip to main content

Advertisement

Springer Nature Link
Log in

Neurodegenerative disorders associated with diabetes mellitus

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B1 deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. McKusick VA, et al (2004) Online Mendelian inheritance in man (OMIM). McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, National Center for Biotechnology Information, National Library of Medicine, Bethesda (http://www.ncbi.nlm.nih.gov/omim/)

  2. Werner CWO (1904) Über Katarakt in Verbindung mit Sklerodermie. Schmidt & Klaunig, Kiel

  3. Field JB, Loube SD (1960) Observations concerning the diabetes mellitus associated with Werner’s syndrome. Metabolism 9:118–124

    CAS  PubMed  Google Scholar 

  4. Müller H (1990) Recessively inherited deficiencies predisposing to cancer. Anticancer Res 10:513–518

    PubMed  Google Scholar 

  5. Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787

    Article  CAS  PubMed  Google Scholar 

  6. Reaven GM, Bernstein R, Davis B, Olefsky JM (1976) Nonketotic diabetes mellitus: insulin deficiency or insulin resistance? Am J Med 60:80–88

    Article  CAS  PubMed  Google Scholar 

  7. Ashcroft FM, Proks P, Smith PA, Ammala C, Bokvist K, Rorsman P (1994) Stimulus-secretion coupling in pancreatic beta cells. J Cell Biochem 55:54–65

    CAS  PubMed  Google Scholar 

  8. Kahn CR (1994) Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43:1066–1084

    CAS  PubMed  Google Scholar 

  9. Schwartz MW, Kahn SE (1999) Insulin resistance and obesity. Nature 402:860–861

    Article  CAS  PubMed  Google Scholar 

  10. Clark A, Jones LC, de Koning E, Hansen BC, Matthews DR (2001) Decreased insulin secretion in type 2 diabetes: a problem of cellular mass or function? Diabetes 50 [Suppl 1]:S169–S171

  11. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110

    Google Scholar 

  12. Ashcroft F, Rorsman P (2004) Type 2 diabetes mellitus: not quite exciting enough? Hum Mol Genet 13 [Suppl 1]:R21–31

    Google Scholar 

  13. Alberti KGM.M, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. I. diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation. Diabet Med 15:539–553

    CAS  PubMed  Google Scholar 

  14. Kelley DE, He J, Menshikova EV, Ritov VB (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51:2944–2950

    Google Scholar 

  15. Yechoor VK, Patti ME, Saccone R, Kahn CR (2002) Coordinated patterns of gene expression for substrate and energy metabolism in skeletal muscle of diabetic mice. Proc Natl Acad Sci USA 99:10587–10592

    Article  CAS  PubMed  Google Scholar 

  16. Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471

    Article  CAS  PubMed  Google Scholar 

  17. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142

    Article  CAS  PubMed  Google Scholar 

  18. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671

    Article  CAS  PubMed  Google Scholar 

  19. Logan JIH, Harveyson KB, Wisdom GB, Hughes AE, Archbold GPR (1994) Hereditary caeruloplasmin deficiency, dementia and diabetes mellitus. Q J Med 87:663–670

    CAS  Google Scholar 

  20. Kohno S, Miyajima H, Takahashi Y, Suzuki H, Hishida A (2000) Defective electron transfer in complexes I and IV in patients with aceruloplasminemia. J Neurol Sci 182:57–60

    Article  CAS  PubMed  Google Scholar 

  21. Miyajima H, Kono S, Takahashi Y, Sugimoto M (2002) Increased lipid peroxidation and mitochondrial dysfunction in aceruloplasminemia brains. Blood Cells Mol Dis 29:433–438

    Article  CAS  PubMed  Google Scholar 

  22. Frerichs FT von (1861) Klinik der Leberkrankheiten. Vieweg & Sohn, Braunschweig

  23. Westphal KFO (1883) Über eine dem Bilde der cerebrospinalen grauen Degeneration ähnliche Erkrankung des centralen Nervensystems ohne anatomischen Befund, nebst einigen Bemerkungen über paradoxe Contraktion. Arch Psychiatr Nervenkr 14:87–134, 767–769

    Google Scholar 

  24. Wilson SAK (1912) Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain 34:295–507

    Google Scholar 

  25. Trousseau A (1861–1862) Clinique médicale de l’Hôtel-Dieu de Paris. Baillière, Paris

  26. Collin GBM, Marshall JD, Ikeda A, So WV, Russell-Eggitt I, Maffei P, Beck S, Boerkoel CF, Sicolo N, Martin M, et al (2002) Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome. Nat Genet 31:74–78

    CAS  PubMed  Google Scholar 

  27. Hearn TR, Renforth GL, Spalluto C, Hanley NA, Piper K, Brickwood S, White C, Connolly V, Taylor JFN, Russell-Eggitt I, et al (2002) Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome. Nat Genet 31:79–83

    CAS  PubMed  Google Scholar 

  28. t’Hart LM, Maassen JA, Dekker JM, Heine RJ (2003) Lack of association between gene variants in the ALMS1 gene and type 2 diabetes mellitus. Diabetologia 46:1023–1024

    Google Scholar 

  29. Quiros-Tejeira RE, Vargas J, Ament ME (2001) Early-onset liver disease complicated with acute liver failure in Alstrom syndrome. Am J Med Genet 101:9–11

    Article  CAS  PubMed  Google Scholar 

  30. Louis-Bar M (1941) Sur un syndrome progressif comprenant des télangiectasies capillaires cutanées et conjonctivales symétriques, à disposition naevoïde et des troubles cérébelleux. Confin Neurol 4:32–42

    Google Scholar 

  31. Centerwall WR, Miller MM (1958) Ataxia, telangiectasia, and sinopulmonary infections; a syndrome of slowly progressive deterioration in childhood. AMA J Dis Child:385–396

    Google Scholar 

  32. Savitsky KB-S, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, et al (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749–1753

    CAS  PubMed  Google Scholar 

  33. Kastan MB, Lim DS, Kim ST, Xu B, Canman C (2000) Multiple signaling pathways involving ATM. Cold Spring Harbor Symp Q Biol 65:521–526

    CAS  Google Scholar 

  34. Kastan MB, Lim DS (2000) The many substrates and functions of ATM. Nat Rev Mol Cell Biol 1:179–186

    CAS  PubMed  Google Scholar 

  35. Bar RS, Levis WR, Rechler MM, Harrison LC, Siebert C, Podskalny J, Roth J, Muggeo M (1978) Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors. N Engl J Med 298:1164–1171

    CAS  PubMed  Google Scholar 

  36. Schalch DSM, McFarlin DE, Barlow MH (1970) An unusual form of diabetes mellitus in ataxia-telangiectasia. N Engl J Med 282:1396–1402

    CAS  PubMed  Google Scholar 

  37. Morrell D, Chase CL, Kupper LL, Swift M (1986) Diabetes mellitus in ataxia-telangiectasia, Fanconi anemia, xeroderma pigmentosum, common variable immune deficiency, and severe combined immune deficiency families. Diabetes 35:143–147

    Google Scholar 

  38. Robinson S, Kessling A (1992) Diabetes secondary to genetic disorders. Baillieres Clin Endocrinol Metab 6:867–898

    CAS  PubMed  Google Scholar 

  39. Blevins LS Jr, Gebhart SS (1996) Insulin-resistant diabetes mellitus in a black woman with ataxia-telangiectasia. South Med J 89:619–621

    PubMed  Google Scholar 

  40. Swift M, Reitnauer PJ, Morrell D, Chase CL (1987) Breast and other cancers in families with ataxia-telangiectasia. N Engl J Med 316:1289–1294

    CAS  PubMed  Google Scholar 

  41. Pippard EC, Hall AJ, Barker DJ, Bridges BA (1988) Cancer in homozygotes and heterozygotes of ataxia-telangiectasia and xeroderma pigmentosum in Britain. Cancer Res 48:2929–2932

    CAS  PubMed  Google Scholar 

  42. Swift M, Morrell D, Massey RB, Chase CL (1991) Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325:1831–1836

    CAS  PubMed  Google Scholar 

  43. Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, et al (1996) Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86:159–171

    CAS  PubMed  Google Scholar 

  44. Elson A, Wang Y, Daugherty CJ, Morton CC, Zhou F, Campos-Torres J, Leder P (1996) Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proc Natl Acad Sci USA 93:13084–13089

    Article  CAS  PubMed  Google Scholar 

  45. Xu Y, Ashley T, Brainerd EE, Bronson RT, Meyn MS, Baltimore D (1996) Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev 10:2411–2422

    CAS  PubMed  Google Scholar 

  46. Alzheimer A (1907) Ueber eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiat Med 64

  47. Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13:72–78

    CAS  PubMed  Google Scholar 

  48. Eckert A, Keil U, Marques CA, Bonert A, Frey C, Schüssel K, Müller WE (2003) Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease. Biochem Pharmacol 66:1627–1634

    Article  CAS  PubMed  Google Scholar 

  49. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249

    CAS  PubMed  Google Scholar 

  50. Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ, et al (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 43:1467–1472

    CAS  PubMed  Google Scholar 

  51. Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC Jr, Rimmler JB, Locke PA, Conneally PM, Schmader KE, et al (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet 7:180–184

    PubMed  Google Scholar 

  52. Bertram L, Tanzi RE (2004) Alzheimer’s disease: one disorder, too many genes? Hum Mol Genet 13 [Suppl 1]:R135–R141

    Google Scholar 

  53. Thinakaran G, Borchelt DR, Lee MK, Slunt HH, Spitzer L, Kim G, Ratovitsky T, Davenport F, Nordstedt C, Seeger M, et al (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17:181–190

    CAS  PubMed  Google Scholar 

  54. Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, et al (1995) Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 376:775–778

    CAS  PubMed  Google Scholar 

  55. Opie EL (1901) The relation of diabetes mellitus to lesions of the pancreas: hyaline degeneration of the islands of Langerhans. J Exp Med 5:527–540

    Google Scholar 

  56. Mosselman S, Hoppener JW, Zandberg J, van Mansfeld AD, Geurts van Kessel AH, Lips CJ, Jansz HS (1988) Islet amyloid polypeptide: identification and chromosomal localization of the human gene. FEBS Lett 239:227–232

    Article  CAS  PubMed  Google Scholar 

  57. Hoppener JW, Ahren B, Lips CJ (2000) Islet amyloid and type 2 diabetes mellitus. N Engl J Med 343:411–419

    CAS  PubMed  Google Scholar 

  58. Janson J, Laedtke T, Parisi JE, O’Brien P, Petersen RC, Butler PC (2004) Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53:474–481

    Google Scholar 

  59. Razay G, Wilcock GK (1994) Hyperinsulinaemia and Alzheimer’s disease. Age Ageing 23:396–399

    CAS  PubMed  Google Scholar 

  60. Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O’Brien PC, Palumbo PJ (1997) Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol 145:301–308

    CAS  PubMed  Google Scholar 

  61. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM (1999) Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology 53:1937–1942

    CAS  PubMed  Google Scholar 

  62. Stolk RP, Breteler MM, Ott A, Pols HA, Lamberts SW, Grobbee DE, Hofman A (1997) Insulin and cognitive function in an elderly population. The Rotterdam Study. Diabetes Care 20:792–795

    Google Scholar 

  63. Watson GS, Peskind ER, Asthana S, Purganan K, Wait C, Chapman D, Schwartz MW, Plymate S, Craft S (2003) Insulin increases CSF Abeta42 levels in normal older adults. Neurology 60:1899–1903

    CAS  PubMed  Google Scholar 

  64. Wolozin B (2004) Cholesterol and the biology of Alzheimer’s disease. Neuron 41:7–10

    Article  CAS  PubMed  Google Scholar 

  65. Janson J, Soeller WC, Roche PC, Nelson RT, Torchia AJ, Kreutter DK, Butler PC (1996) Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proc Natl Acad Sci USA 93:7283–7288

    Article  CAS  PubMed  Google Scholar 

  66. Verchere CB, D’Alessio DA, Palmiter RD, Weir GC, Bonner-Weir S, Baskin DG, Kahn SE (1996) Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide. Proc Natl Acad Sci USA 93:3492–3496

    Article  CAS  PubMed  Google Scholar 

  67. Ahren B, Oosterwijk C, Lips CJ, Hoppener JW (1998) Transgenic overexpression of human islet amyloid polypeptide inhibits insulin secretion and glucose elimination after gastric glucose gavage in mice. Diabetologia 41:1374–1380

    Google Scholar 

  68. Hoppener JW, Oosterwijk C, Nieuwenhuis MG, Posthuma G, Thijssen JH, Vroom TM, Ahren B, Lips CJ (1999) Extensive islet amyloid formation is induced by development of type II diabetes mellitus and contributes to its progression: pathogenesis of diabetes in a mouse model. Diabetologia 42:427–434

    Google Scholar 

  69. Gebre-Medhin S, Mulder H, Pekny M, Westermark G, Tornell J, Westermark P, Sundler F, Ahren B, Betsholtz C (1998) Increased insulin secretion and glucose tolerance in mice lacking islet amyloid polypeptide (amylin). Biochem Biophys Res Commun 250:271–277

    Article  CAS  PubMed  Google Scholar 

  70. Farris WM, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE, Selkoe DJ, Guenette S (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci USA 100:4162–4167

    CAS  PubMed  Google Scholar 

  71. Bardet G (1920) Sur un syndrome d’obésité infantile avec polydactylie et rétinite pigmentaire (contribution à l’étude des formes cliniques de l’obésité hypophysaire). Paris

  72. Biedl A (1922) Ein Geschwisterpaar mit adiposo-genitaler dystrophie. Dtsch Med Wochenschr 48:1630

    Google Scholar 

  73. Katsanis N (2004) The oligogenic properties of Bardet-Biedl syndrome. Hum Mol Genet 13 [Suppl 1]:R65–R71

    Google Scholar 

  74. Green JSP, Parfrey PS, Harnett JD, Farid NR, Cramer BC, Johnson G, Heath O, McManamon PJ, O’Leary E, Pryse-Phillips W (1989) The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome. N Engl J Med 321:1002–1009

    CAS  PubMed  Google Scholar 

  75. Ammann F (1970) Investigations cliniques et génétiques sur le syndrome de Bardet-Biedl en Suisse. J Genet Hum 18 [Suppl]:1–31

    Google Scholar 

  76. Croft JBS, and Swift M (1990) Obesity, hypertension, and renal disease in relatives of Bardet-Biedl syndrome sibs. Am J Med Genet 36:37–42

    CAS  PubMed  Google Scholar 

  77. Melberg A, Hetta J, Dahl N, Nennesmo I, Bengtsson M, Wibom R, Grant C, Gustavson KH, Lundberg PO (1995) Autosomal dominant cerebellar ataxia deafness and narcolepsy. J Neurol Sci 134:119–129

    Article  CAS  PubMed  Google Scholar 

  78. Melberg A, Dahl N, Hetta J, Valind S, Nennesmo I, Lundberg PO, Raininko R (1999) Neuroimaging study in autosomal dominant cerebellar ataxia, deafness, and narcolepsy. Neurology 53:2190–2192

    CAS  PubMed  Google Scholar 

  79. Lejeune J, Gautier M, Turpin R (1959) Etude des chromosomes somatiques de neuf enfants mongoliens. C R Acad Sci 248:1721–1722

    CAS  Google Scholar 

  80. Down JLH (1866) Observations on an ethnic classification of idiots. London Hosp Clin Lecture Rep 3:259

    Google Scholar 

  81. Burch PR, Milunsky A (1969) Early-onset diabetes mellitus in the general and Down’s syndrome populations. Genetics, aetiology, and pathogenesis. Lancet I:554–558

    Article  Google Scholar 

  82. Epstein CJ (1989) Down syndrome, trisomy 21. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) Metabolic basis of inherited disease. McGraw-Hill, New York, pp 291–326

  83. Prince J, Jia S, Bave U, Anneren G, Oreland L (1994) Mitochondrial enzyme deficiencies in Down’s syndrome. J Neural Transm Park Dis Dement Sect 8:171–181

    CAS  PubMed  Google Scholar 

  84. Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H, Yankner BA (2002) Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down’s syndrome. Neuron 33:677–688

    Article  CAS  PubMed  Google Scholar 

  85. Arbuzova S, Hutchin T, Cuckle H (2002) Mitochondrial dysfunction and Down’s syndrome. Bioessays 24:681–684

    Article  PubMed  Google Scholar 

  86. Altafaj XD M, Baamonde C, Marti E, Visa J, Guimera J, Oset M, Gonzalez JR, Florez J, Fillat C, Estivill X (2001) Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down’s syndrome. Hum Mol Genet 10:1915–1923

    Article  CAS  PubMed  Google Scholar 

  87. Shinohara T, Tomizuka K, Miyabara S, Takehara S, Kazuki Y, Inoue J, Katoh M, Nakane H, Iino A, Ohguma A, et al (2001) Mice containing a human chromosome 21 model behavioral impairment and cardiac anomalies of Down’s syndrome. Hum Mol Genet 10:1163–1175

    Article  CAS  PubMed  Google Scholar 

  88. Feigenbaum AB, Bergeron C, Richardson R, Wherret J, Robinson B, Weksberg R (1994) Premature atherosclerosis with photomyoclonic epilepsy, deafness, diabetes mellitus, nephropathy, and neurodegenerative disorder in two brothers: a new syndrome? Am J Med Genet 49:118–124

    CAS  PubMed  Google Scholar 

  89. Friedreich N (1863) Ueber degenerative Atrophie der spinalen Hinterstränge. Virchows Arch Pathol Anat 26:391–419

    Google Scholar 

  90. Boyer SH, Chisholm AW, McKusick VA (1962) Cardiac aspects of Friedreich’s ataxia. Circulation 25:493–505

    PubMed  Google Scholar 

  91. Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, et al (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271:1423–1427

    CAS  PubMed  Google Scholar 

  92. Koutnikova H, Campuzano V, Foury F, Dolle P, Cazzalini O, Koenig M (1997) Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nat Genet 16:345–351

    CAS  PubMed  Google Scholar 

  93. Ohshima K, Kang S, Larson JE, Wells RD (1996) Cloning, characterization, and properties of seven triplet repeat DNA sequences. J Biol Chem 271:16773–16783

    Article  CAS  PubMed  Google Scholar 

  94. Ohshima K, Montermini L, Wells RD, Pandolfo M (1998) Inhibitory effects of expanded GAA.TTC triplet repeats from intron I of the Friedreich ataxia gene on transcription and replication in vivo. J Biol Chem 273:14588–14595

    CAS  PubMed  Google Scholar 

  95. Bidichandani SI, Ashizawa T, Patel PI (1998) The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am J Hum Genet 62:111–121

    CAS  PubMed  Google Scholar 

  96. Parniewski P, Bacolla A, Jaworski A, Wells RD (1999) Nucleotide excision repair affects the stability of long transcribed (CTG*CAG) tracts in an orientation-dependent manner in Escherichia coli. Nucleic Acids Res 27:616–623

    Article  CAS  PubMed  Google Scholar 

  97. Sakamoto N, Chastain PD, Parniewski P, Ohshima K, Pandolfo M, Griffith JD, and Wells RD (1999) Sticky DNA: self-association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich’s ataxia. Mol Cell 3:465–475

    CAS  PubMed  Google Scholar 

  98. Koutnikova H, Campuzano V, Koenig M (1998) Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase. Hum Mol Genet 7:1485–1489

    Article  CAS  PubMed  Google Scholar 

  99. Campuzano V, Montermini L, Lutz Y, Cova L, Hindelang C, Jiralerspong S, Trottier Y, Kish SJ, Faucheux B, Trouillas P, et al (1997) Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 6:1771–1780

    CAS  PubMed  Google Scholar 

  100. Mühlenhoff U, Richhardt N, Ristow M, Kispal G, Lill R (2002) The yeast frataxin homologue Yfh1p plays a specific role in the maturation of cellular Fe/S proteins. Hum Mol Genet 11:2025–2036

    Article  PubMed  Google Scholar 

  101. Mühlenhoff U, Gerber J, Richhardt N, Lill R (2003) Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. EMBO J 22:4815–4825

    Article  PubMed  Google Scholar 

  102. Gerber J, Muhlenhoff U, Lill R (2003) An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1. EMBO Rep 4:906–911

    Article  CAS  PubMed  Google Scholar 

  103. Ristow M, Pfister MF, Yee AJ, Schubert M, Michael L, Zhang CY, Ueki K, Michael MD, 2nd, Lowell BB, Kahn CR (2000) Frataxin activates mitochondrial energy conversion and oxidative phosphorylation. Proc Natl Acad Sci USA 97:12239–12243

    Article  CAS  PubMed  Google Scholar 

  104. Adinolfi S, Trifuoggi M, Politou AS, Martin S, Pastore A (2002) A structural approach to understand the iron-binding properties of phylogenetically different frataxins. Hum Mol Genet 11:1865–1877

    Article  CAS  PubMed  Google Scholar 

  105. Dhe-Paganon S, Shigeta R, Chi YI, Ristow M, Shoelson SE (2000) Crystal structure of human frataxin. J Biol Chem 275:30753–30756

    Article  CAS  PubMed  Google Scholar 

  106. Branda SS, Yang Z, Chew A, Isaya G (1999) Mitochondrial intermediate peptidase and the yeast frataxin homolog together maintain mitochondrial iron homeostasis in Saccharomyces cerevisiae. Hum Mol Genet 8:1099–1110

    Article  CAS  PubMed  Google Scholar 

  107. Isaya G, Adamec J, Rusnak F, Owen WG, Naylor S, Benson LM (1999) Frataxin is an iron storage protein. Am J Hum Genet 65 [Suppl]:A167

  108. Radisky DC, Babcock MC, Kaplan J (1999) The yeast frataxin homologue mediates mitochondrial iron efflux. Evidence for a mitochondrial iron cycle. J Biol Chem 274:4497–4499

    Article  CAS  PubMed  Google Scholar 

  109. Adamec J, Rusnak F, Owen WG, Naylor S, Benson LM, Gacy AM, Isaya G (2000) Iron-dependent self-assembly of recombinant yeast frataxin: implications for Friedreich ataxia. Am J Hum Genet 67:549–562

    Article  CAS  PubMed  Google Scholar 

  110. Gordon N (2000) Friedreich’s ataxia and iron metabolism. Brain Dev 22:465–468

    Article  CAS  PubMed  Google Scholar 

  111. Gakh O, Adamec J, Gacy AM, Twesten RD, Owen WG, Isaya G (2002) Physical evidence that yeast frataxin is an iron storage protein. Biochemistry 41:6798–6804

    Article  CAS  PubMed  Google Scholar 

  112. Schulz JB, Dehmer T, Schöls L, Mende H, Hardt C, Vorgerd M, Burk K, Matson W, Dichgans J, Beal MF, et al (2000) Oxidative stress in patients with friedreich ataxia. Neurology 55:1719–1721

    CAS  PubMed  Google Scholar 

  113. Emond M, Lepage G, Vanasse M, Pandolfo M (2000) Increased levels of plasma malondialdehyde in friedreich ataxia. Neurology 55:1752–1753

    CAS  PubMed  Google Scholar 

  114. Cossee M, Puccio H, Gansmuller A, Koutnikova H, Dierich A, LeMeur M, Fischbeck K, Dolle P, Koenig M (2000) Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum Mol Genet 9:1219–1226

    Article  CAS  PubMed  Google Scholar 

  115. Puccio H, Simon D, Cossee M, Criqui-Filipe P, Tiziano F, Melki J, Hindelang C, Matyas R, Rustin P, Koenig M (2001) Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet 27:181–186

    Article  CAS  PubMed  Google Scholar 

  116. Wong A, Yang J, Cavadini P, Gellera C, Lonnerdal B, Taroni F, Cortopassi G (1999) The Friedreich’s ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis. Hum Mol Genet 8:425–430

    Article  CAS  PubMed  Google Scholar 

  117. Chantrel-Groussard K, Geromel V, Puccio H, Koenig M, Munnich A, Rötig A, Rustin P (2001) Disabled early recruitment of antioxidant defenses in Friedreich’s ataxia. Hum Mol Genet 10:2061–2067

    Article  CAS  PubMed  Google Scholar 

  118. Shoichet SA, Bäumer AT, Stamenkovic D, Sauer H, Pfeiffer AF, Kahn CR, Müller-Wieland D, Richter C, Ristow M (2002) Frataxin promotes antioxidant defense in a thiol-dependent manner resulting in diminished malignant transformation in vitro. Hum Mol Genet 11:815–821

    Article  CAS  PubMed  Google Scholar 

  119. Barr H, Page R, Taylor W (1986) Primary small bowel ganglioneuroblastoma and Friedreich’s ataxia. J R Soc Med 79:612–613

    CAS  PubMed  Google Scholar 

  120. Ackroyd R, Shorthouse AJ, Stephenson TJ (1996) Gastric carcinoma in siblings with Friedreich’s ataxia. Eur J Surg Oncol 22:301–303

    CAS  PubMed  Google Scholar 

  121. Kidd A, Coleman R, Whiteford M, Barron LH, Simpson SA, Haites NE (2001) Breast cancer in two sisters with Friedreich’s ataxia. Eur J Surg Oncol 27:512–514

    Article  CAS  PubMed  Google Scholar 

  122. Hewer RL, Robinson N (1968) Diabetes mellitus in Friedreich’s ataxia. J Neurol Neurosurg Psychiatry 31:226–231

    CAS  PubMed  Google Scholar 

  123. Hewer RL (1968) Study of fatal cases of Friedreich’s ataxia. BMJ 3:649–652

    CAS  PubMed  Google Scholar 

  124. Finocchiaro G, Baio G, Micossi P, Pozza G, di Donato S (1988) Glucose metabolism alterations in Friedreich’s ataxia. Neurology 38:1292–1296

    CAS  PubMed  Google Scholar 

  125. Khan RJ, Andermann E, Fantus IG (1986) Glucose intolerance in Friedreich’s ataxia: association with insulin resistance and decreased insulin binding. Metabolism 35:1017–1023

    CAS  PubMed  Google Scholar 

  126. Hebinck J, Hardt C, Schöls L, Vorgerd M, Briedigkeit L, Kahn CR, Ristow M (2000) Heterozygous expansion of the GAA tract of the X25/frataxin gene is associated with insulin resistance in humans. Diabetes 49:1604–1607

    Google Scholar 

  127. Ristow M, Giannakidou E, Hebinck J, Busch K, Vorgerd M, Kotzka J, Knebel B, Müller-Berghaus J, Epplen C, Pfeiffer A, et al (1998) An association between NIDDM and a GAA trinucleotide repeat polymorphism in the X25/frataxin (Friedreich’s ataxia) gene. Diabetes 47:851–854

    Google Scholar 

  128. Dupont S, Dubois D, Vionnet N, Boitard C, Caillat-Zucman S, Timsit J, Froguel P (1998) No association between the Friedreich’s ataxia gene and NIDDM in the French population. Diabetes 47:1654–1656

    Google Scholar 

  129. Dalgaard LT, Hansen T, Urhammer SA, Clausen JO, Eiberg H, Pedersen O (1999) Intermediate expansions of a GAA repeat in the frataxin gene are not associated with type 2 diabetes or altered glucose-induced beta-cell function in Danish Caucasians. Diabetes 48:914–917

    Google Scholar 

  130. t’Hart LM, Ruige JB, Dekker JM, Stehouwer CD, Maassen JA, Heine RJ (1999) Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene. Diabetes 48:924–926

    Google Scholar 

  131. Lynn S, Hattersley AT, McCarthy MI, Frayling TM, Turnbull DM, Walker M (2000) Intermediate expansions of a X25/frataxin gene GAA repeat and type II diabetes: assessment using parent-offspring trios. Diabetologia 43:384–385

    Google Scholar 

  132. Shadrina MI, Miloserdova OV, Slominskii PA, Balabolkin MI, Limborskaya SA (2002) Association of polymorphic trinucleotide repeats (GAA)n of the frataxin gene with diabetes mellitus type 2 in the Moscow population. Mol Biol (Mosk) 36:37–39

    Google Scholar 

  133. Hanis CL, Boerwinkle E, Chakraborty R, Ellsworth DL, Concannon P, Stirling B, Morrison VA, Wapelhorst B, Spielman RS, Gogolin-Ewens KJ, et al (1996) A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet 13:161–166

    CAS  PubMed  Google Scholar 

  134. Pratley RE, Thompson DB, Prochazka M, Baier L, Mott D, Ravussin E, Sakul H, Ehm MG, Burns DK, Foroud T, et al (1998) An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest 101:1757–1764

    CAS  Google Scholar 

  135. Luo TH, Zhao Y, Li G, Yuan WT, Zhao JJ, Chen JL, Huang W, Luo M (2001) A genome-wide search for type II diabetes susceptibility genes in Chinese Hans. Diabetologia 44:501–506

    Google Scholar 

  136. Lindgren CM, Mahtani MM, Widen E, McCarthy MI, Daly MJ, Kirby A, Reeve MP, Kruglyak L, Parker A, Meyer J, et al (2002) Genomewide search for type 2 diabetes mellitus susceptibility loci in Finnish families: the Botnia study. Am J Hum Genet 70:509–516

    Article  CAS  PubMed  Google Scholar 

  137. Ristow M, Mulder H, Pomplun D, Schulz TJ, Müller-Schmehl K, Krause A, Fex M, Puccio H, Müller J, Isken F, et al (2003) Frataxin-deficiency in pancreatic islets causes diabetes due to loss of beta-cell mass. J Clin Invest 112:527–534

    Article  CAS  PubMed  Google Scholar 

  138. Herrmann C Jr, Aguilar MJ, Sacks OW (1964) Hereditary photomyoclonus associated with diabetes mellitus, deafness, nephropathy, and cerebral dysfunction. Neurology 14:212–222

    PubMed  Google Scholar 

  139. Huntington G (1872) On chorea. Med Surg Reporter 26:317–321

    Google Scholar 

  140. Mazziotta JC, Phelps ME, Pahl JJ, Huang SC, Baxter LR, Riege WH, Hoffman JM, Kuhl DE, Lanto AB, Wapenski JA, et al (1987) Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington’s disease. N Engl J Med 316:357–362

    CAS  PubMed  Google Scholar 

  141. Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983

    PubMed  Google Scholar 

  142. Djousse L, Knowlton B, Hayden M, Almqvist EW, Brinkman R, Ross C, Margolis R, Rosenblatt A, Durr A, Dode C, et al (2003) Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease. Am J Med Genet 119A:279–282

    Article  CAS  PubMed  Google Scholar 

  143. Dyer RB, McMurray CT (2001) Mutant protein in Huntington disease is resistant to proteolysis in affected brain. Nat Genet 29:270–278

    Article  CAS  PubMed  Google Scholar 

  144. Arenas J, Campos Y, Ribacoba R, Martin MA, Rubio JC, Ablanedo P, Cabello A (1998) Complex I defect in muscle from patients with Huntington’s disease. Ann Neurol 43:397–400

    CAS  PubMed  Google Scholar 

  145. Bogdanov MB, Andreassen OA, Dedeoglu A, Ferrante RJ, Beal MF (2001) Increased oxidative damage to DNA in a transgenic mouse model of Huntington’s disease. J Neurochem 79:1246–1249

    Article  CAS  PubMed  Google Scholar 

  146. Schapira AH (2002) Primary and secondary defects of the mitochondrial respiratory chain. J Inherit Metab Dis 25:207–214

    Article  CAS  PubMed  Google Scholar 

  147. Podolsky S, Leopold NA, Sax DS (1972) Increased frequency of diabetes mellitus in patients with Huntington’s chorea. Lancet I:1356–1358

    Article  Google Scholar 

  148. Farrer LA (1985) Diabetes mellitus in Huntington disease. Clin Genet 27:62–67

    CAS  PubMed  Google Scholar 

  149. Podolsky S, Leopold NA (1977) Abnormal glucose tolerance and arginine tolerance tests in Huntington’s disease. Gerontology 23:55–63

    CAS  PubMed  Google Scholar 

  150. Pratley RE, Salbe AD, Ravussin E, Caviness JN (2000) Higher sedentary energy expenditure in patients with Huntington’s disease. Ann Neurol 47:64–70

    Article  CAS  PubMed  Google Scholar 

  151. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, et al (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506

    CAS  PubMed  Google Scholar 

  152. Hurlbert MS, Zhou W, Wasmeier C, Kaddis FG, Hutton JC, Freed CR (1999) Mice transgenic for an expanded CAG repeat in the Huntington’s disease gene develop diabetes. Diabetes 48:649–651

    Google Scholar 

  153. Jenkins BG, Klivenyi P, Kustermann E, Andreassen OA, Ferrante RJ, Rosen BR, Beal MF (2000) Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington’s disease mice. J Neurochem 74:2108–2119

    Article  CAS  PubMed  Google Scholar 

  154. Andreassen OA, Dedeoglu A, Stanojevic V, Hughes DB, Browne SE, Leech CA, Ferrante RJ, Habener JF, Beal MF, Thomas MK (2002) Huntington’s disease of the endocrine pancreas: insulin deficiency and diabetes mellitus due to impaired insulin gene expression. Neurobiol Dis 11:410–424

    Article  CAS  PubMed  Google Scholar 

  155. Miller TW, Shirley TL, Wolfgang WJ, Kang X, Messer A (2003) DNA vaccination against mutant huntingtin ameliorates the HDR6/2 diabetic phenotype. Mol Ther 7:572–579

    Article  CAS  PubMed  Google Scholar 

  156. Fain JN, Del Mar NA, Meade CA, Reiner A, Goldowitz D (2001) Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington’s disease mutation. Hum Mol Genet 10:145–152

    Article  CAS  PubMed  Google Scholar 

  157. Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, Dunnett SB, Morton AJ (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J Neurosci 19:3248–3257

    CAS  PubMed  Google Scholar 

  158. Kearns TPS, Sayre GP (1958) Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases. Arch Ophthalmol 60:280–289

    CAS  Google Scholar 

  159. Poulton J, O’Rahilly S, Morten KJ, Clark A (1995) Mitochondrial DNA, diabetes and pancreatic pathology in Kearns-Sayre syndrome. Diabetologia 38:868–871

    Google Scholar 

  160. Piccolo G, Aschei M, Ricordi A, Banfi P, Lo Curto F, Fratino P (1989) Normal insulin receptors in mitochondrial myopathies with ophthalmoplegia. J Neurol Sci 94:163–172

    Article  CAS  PubMed  Google Scholar 

  161. Iannaccone ST, Griggs RC, Markesbery WR, Joynt RJ (1974) Familial progressive external ophthalmoplegia and ragged-red fibers. Neurology 24:1033–1038

    CAS  PubMed  Google Scholar 

  162. McKenzie M, Trounce IA, Cassar CA, Pinkert CA (2004) Production of homoplasmic xenomitochondrial mice. Proc Natl Acad Sci USA 101:1685–1690

    Article  CAS  PubMed  Google Scholar 

  163. Klinefelter HF, Reifenstein EC, et al (1942) Syndrome characterized by gynaecomastia, aspermatogenesis without A-Leydigism and increased excretion of follicle-stimulating hormone. J Clin Endocrinol Metab 2:615–627

    CAS  Google Scholar 

  164. Gomez-Acebo J, Parrilla R, Abrisqueta JA, Pozuelo V (1968) Fine structure of spermatogenesis in Klinefelter’s syndrome. J Clin Endocrinol Metab 28:1287–1294

    CAS  PubMed  Google Scholar 

  165. Oikawa H, Tun Z, Young DR, Ozawa H, Yamazaki K, Tanaka E, Honda K (2002) The specific mitochondrial DNA polymorphism found in Klinefelter’s syndrome. Biochem Biophys Res Commun 297:341–345

    Article  CAS  PubMed  Google Scholar 

  166. Jackson IM, Buchanan KD, McKiddie MT, Prentice CR (1966) Carbohydrate metabolism in Klinefelter’s syndrome. J Endocrinol 35:169–172

    CAS  PubMed  Google Scholar 

  167. Zuppinger K, Engel E, Forbes AP, Mantooth L, Claffey J (1967) Klinefelter’s syndrome, a clinical and cytogenetic study in twenty-four cases. Acta Endocrinol (Copenh) 54 [Suppl 113]:5

  168. Burch PR (1969) Klinefelter’s syndrome, dizygotic twinning and diabetes mellitus. Nature 221:175–177

    CAS  PubMed  Google Scholar 

  169. Hanna MG, Nelson I, Sweeney MG, Cooper JM, Watkins PJ, Morgan-Hughes JA, Harding AE (1995) Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation. Am J Hum Genet 56:1026–1033

    CAS  PubMed  Google Scholar 

  170. Hao H, Bonilla E, Manfredi G, DiMauro S, Moraes CT (1995) Segregation patterns of a novel mutation in the mitochondrial tRNA glutamic acid gene associated with myopathy and diabetes mellitus. Am J Hum Genet 56:1017–1025

    CAS  PubMed  Google Scholar 

  171. Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA (Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653

    CAS  PubMed  Google Scholar 

  172. Kobayashi Y, Momoi MY, Tominaga K, Momoi T, Nihei K, Yanagisawa M, Kagawa Y, Ohta S (1990) A point mutation in the mitochondrial tRNA (Leu)(UUR) gene in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Biochem Biophys Res Commun 173:816–822

    CAS  PubMed  Google Scholar 

  173. Kressmann F (1976) Association diabète et surdité: à propos d’une famille atteinte de cette double tare. Thesis, University of Bordeaux II

  174. Ballinger SW, Shoffner JM, Hedaya EV, Trounce I, Polak MA, Koontz DA, Wallace DC (1992) Maternally transmitted diabetes and deafness associated with a 10.4\kb mitochondrial DNA deletion. Nat Genet 1:11–15

    CAS  PubMed  Google Scholar 

  175. Ouweland JM van den, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, van de Kamp JJ, Maassen JA (1992) Mutation in mitochondrial tRNA (Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1:368–371

    PubMed  Google Scholar 

  176. Reardon W, Ross RJ, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, Trembath RC (1992) Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. Lancet 340:1376–1379

    Article  CAS  PubMed  Google Scholar 

  177. Manouvrier S, Rötig A, Hannebique G, Gheerbrandt J.-D, Royer-Legrain G, Munnich A, Parent M, Grunfeld JP, Largilliere C, Lombes A, et al (1995) Point mutation of the mitochondrial tRNA (leu) gene (A 3243 G) in maternally inherited hypertrophic cardiomyopathy, diabetes mellitus, renal failure, and sensorineural deafness. J Med Genet 32:654–656

    CAS  PubMed  Google Scholar 

  178. Alcolado JC, Alcolado R (1991) Importance of maternal history of non-insulin dependent diabetic patients. BMJ 302:1178–1180

    CAS  PubMed  Google Scholar 

  179. Gerbitz KD, van den Ouweland JM, Maassen JA, Jaksch M (1995) Mitochondrial diabetes mellitus: a review. Biochim Biophys Acta 1271:253–260

    Article  CAS  PubMed  Google Scholar 

  180. Suzuki S, Hinokio Y, Hirai S, Onoda M, Matsumoto M, Ohtomo M, Kawasaki H, Satoh Y, Akai H, Abe K, et al (1994) Pancreatic beta-cell secretory defect associated with mitochondrial point mutation of the tRNA (LEU (UUR)) gene: a study in seven families with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Diabetologia 37:818–825

    Google Scholar 

  181. Velho G, Byrne MM, Clement K, Sturis J, Pueyo ME, Blanche H, Vionnet N, Fiet J, Passa P, Robert JJ, et al (1996) Clinical phenotypes, insulin secretion, and insulin sensitivity in kindreds with maternally inherited diabetes and deafness due to mitochondrial tRNALeu (UUR) gene mutation. Diabetes 45:478–487

    Google Scholar 

  182. Tanaka M, Ino H, Ohno K, Hattori K, Sato W, Ozawa T, Tanaka T, Itoyama S (1990) Mitochondrial mutation in fatal infantile cardiomyopathy. Lancet 336:1452

    CAS  Google Scholar 

  183. Taniike M, Fukushima H, Yanagihara I, Tsukamoto H, Tanaka J, Fujimura H, Nagai T, Sano T, Yamaoka K, Inui K, et al (1992) Mitochondrial tRNA (Ile) mutation in fatal cardiomyopathy. Biochem Biophys Res Commun 186:47–53

    CAS  PubMed  Google Scholar 

  184. Merante F, Myint T, Tein I, Benson L, Robinson BH (1996) An additional mitochondrial tRNA (Ile) point mutation (A-to-G at nucleotide 4295) causing hypertrophic cardiomyopathy. Hum Mutat 8:216–222

    Article  CAS  PubMed  Google Scholar 

  185. Corona P, Lamantea E, Greco M, Carrara F, Agostino A, Guidetti D, Dotti MT, Mariotti C, Zeviani M (2002) Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. Ann Neurol 51:118–122

    Article  CAS  PubMed  Google Scholar 

  186. Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC (1990) Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA (Lys) mutation. Cell 61:931–937

    CAS  PubMed  Google Scholar 

  187. Yoneda M, Tanno Y, Horai S, Ozawa T, Miyatake T, Tsuji S (1990) A common mitochondrial DNA mutation in the t-RNA (Lys) of patients with myoclonus epilepsy associated with ragged-red fibers. Biochem Int 21:789–796

    CAS  PubMed  Google Scholar 

  188. Shoffner JM, Wallace DC (1992) Mitochondrial genetics: principles and practice. Am J Hum Genet 51:1179–1186

    CAS  PubMed  Google Scholar 

  189. Kameoka K, Isotani H, Tanaka K, Kitaoka H, Ohsawa N (1998) Impaired insulin secretion in Japanese diabetic subjects with an A-to-G mutation at nucleotide 8296 of the mitochondrial DNA in tRNA (Lys). Diabetes Care 21:2034–2035

    CAS  PubMed  Google Scholar 

  190. Kameoka K, Isotani H, Tanaka K, Azukari K, Fujimura Y, Shiota Y, Sasaki E, Majima M, Furukawa K, Haginomori S, et al (1998) Novel mitochondrial DNA mutation in tRNA (Lys) (8296A->G) associated with diabetes. Biochem Biophys Res Commun 245:523–527

    Article  CAS  PubMed  Google Scholar 

  191. Lynn S, Wardell T, Johnson MA, Chinnery PF, Daly ME, Walker M, Turnbull DM (1998) Mitochondrial diabetes: investigation and identification of a novel mutation. Diabetes 47:1800–1802

    Google Scholar 

  192. Curschmann H (1905) Über partielle Myotonie unter dem Bilde einer Beschäftigungsneurose und Lähmung. Berl Klin Wochenschr 42:1175–1185

    Google Scholar 

  193. Steinert HHW (1909) Über das klinische und anatomische Bilde des Muskelschwunds des Myotoniker. Dtsch Z Nervenheilkd 37:58–104

    Google Scholar 

  194. Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, et al (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell 68:799–808

    CAS  PubMed  Google Scholar 

  195. Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, et al (1992) Erratum: molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell 69:385

    CAS  Google Scholar 

  196. Carango P, Noble JE, Marks HG, Funanage VL (1993) Absence of myotonic dystrophy protein kinase (DMPK) mRNA as a result of a triplet repeat expansion in myotonic dystrophy. Genomics 18:340–348

    Article  CAS  PubMed  Google Scholar 

  197. Ven PF van der, Jansen G, van Kuppevelt TH, Perryman MB, Lupa M, Dunne PW, ter Laak HJ, Jap PH, Veerkamp JH, Epstein HF, et al (1993) Myotonic dystrophy kinase is a component of neuromuscular junctions. Hum Mol Genet 2:1889–1894

    PubMed  Google Scholar 

  198. Tsilfidis C, MacKenzie AE, Mettler G, Barcelo J, Korneluk RG (1992) Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy. Nat Genet 1:192–195

    CAS  PubMed  Google Scholar 

  199. Charlet BN, Savkur RS, Singh G, Philips AV, Grice EA, Cooper TA (2002) Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell 10:45–53

    Article  PubMed  Google Scholar 

  200. Jamal GA, Weir AI, Hansen S, Ballantyne JP (1986) Myotonic dystrophy. A reassessment by conventional and more recently introduced neurophysiological techniques. Brain 109:1279–1296

    PubMed  Google Scholar 

  201. Spaans F, Jennekens FG, Mirandolle JF, Bijlsma JB, de Gast GC (1986) Myotonic dystrophy associated with hereditary motor and sensory neuropathy. Brain 109:1149–1168

    PubMed  Google Scholar 

  202. Censori B, Provinciali L, Danni M, Chiaramoni L, Maricotti M, Foschi N, Del Pesce M, Salvolini U (1994) Brain involvement in myotonic dystrophy: MRI features and their relationship to clinical and cognitive conditions. Acta Neurol Scand 90:211–217

    CAS  PubMed  Google Scholar 

  203. Kemp GJ, Taylor DJ, Thompson CH, Hands LJ, Rajagopalan B, Styles P, Radda GK (1993) Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise. NMR Biomed 6:302–310

    CAS  PubMed  Google Scholar 

  204. Barnes PR, Kemp GJ, Taylor DJ, Radda GK (1997) Skeletal muscle metabolism in myotonic dystrophy A 31P magnetic resonance spectroscopy study. Brain 120:1699–1711

    Article  PubMed  Google Scholar 

  205. Barbosa J, Nuttall FQ, Kennedy W, Goetz F (1974) Plasma insulin in patients with myotonic dystrophy and their relatives. Medicine (Baltimore) 53:307–323

    Google Scholar 

  206. Reddy S, Smith DB, Rich MM, Leferovich JM, Reilly P, Davis BM, Tran K, Rayburn H, Bronson R, Cros D, et al (1996) Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nat Genet 13:325–335

    CAS  PubMed  Google Scholar 

  207. Jansen G, Groenen PJ, Bachner D, Jap PH, Coerwinkel M, Oerlemans F, van den Broek W, Gohlsch B, Pette D, Plomp JJ, et al (1996) Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nat Genet 13:316–324

    CAS  PubMed  Google Scholar 

  208. Westphal CC (1877) Eigenthümliche mit Einschafen verbundene Anfälle. Arch Psychiat Nervenk 7:681–683

    Google Scholar 

  209. Adie W (1926) Idiopathic narcolepsy: a disease sui generis: with remarks on the mechanism of sleep. Brain 49:257–306

    Google Scholar 

  210. Roberts HJ (1963) The syndrome of narcolepsy and diabetogenic (functional) hyperinsulinism. Observations on 190 patients, with emphasis upon its relationship to obesity, diabetes mellitus and cerebral dysrhythmias. J Fla Med Assoc 50:355–366

    CAS  PubMed  Google Scholar 

  211. Honda Y, Doi Y, Ninomiya R, Ninomiya C (1986) Increased frequency of non-insulin-dependent diabetes mellitus among narcoleptic patients. Sleep 9:254–259

    CAS  PubMed  Google Scholar 

  212. Schuld A, Hebebrand J, Geller F, Pollmacher T (2000) Increased body-mass index in patients with narcolepsy. Lancet 355:1274–1275

    CAS  Google Scholar 

  213. Schuld A, Blum WF, Uhr M, Haack M, Kraus T, Holsboer F, Pollmacher T (2000) Reduced leptin levels in human narcolepsy. Neuroendocrinology 72:195–198

    Article  CAS  PubMed  Google Scholar 

  214. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM (2000) Reduced number of hypocretin neurons in human narcolepsy. Neuron 27:469–474

    CAS  PubMed  Google Scholar 

  215. De Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, 2nd et al (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95:322–327

    PubMed  Google Scholar 

  216. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98:365–376

    CAS  PubMed  Google Scholar 

  217. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E (2000) Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355:39–40

    CAS  PubMed  Google Scholar 

  218. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, et al (2000) A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6:991–997

    CAS  PubMed  Google Scholar 

  219. Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, et al (2003) Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38:701–713

    Article  CAS  PubMed  Google Scholar 

  220. Siebold C, Hansen BE, Wyer JR, Harlos K, Esnouf RE, Svejgaard A, Bell JI, Strominger JL, Jones EY, Fugger L (2004) Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy. Proc Natl Acad Sci USA 101:1999–2004

    Article  CAS  PubMed  Google Scholar 

  221. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, et al (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451

    CAS  PubMed  Google Scholar 

  222. Kayaba Y, Nakamura A, Kasuya Y, Ohuchi T, Yanagisawa M, Komuro I, Fukuda Y, Kuwaki T (2003) Attenuated defense response and low basal blood pressure in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol 285:R581–R593

    PubMed  Google Scholar 

  223. Heine L (1925) Über das familiäre Auftreten von Pseudoglioma congenitum bei zwei Brüdern und Amotio retinae acq. bei Vater und Sohn ünd über Pseudogliom mit Nekrose der Uvea und Retina beim Sohn eines Vaters mit Iritis. Z Augenheilkd 56:155–164

    Google Scholar 

  224. Norrie G (1927) Causes of blindness in children: twenty-five years’ experience of Danish Institutes for the blind. Acta Ophthalmol 5:357–386

    Google Scholar 

  225. Warburg M (1961) Norrie’s disease: a new hereditary bilateral pseudotumour of the retina. Acta Ophthalmol 39:757–772

    Google Scholar 

  226. Warburg M (1963) Norrie’s disease (atrofia bulborum hereditaria). Acta Ophthalmol 41:134–146

    CAS  Google Scholar 

  227. Berger W, Meindl A, van de Pol TJ, Cremers FP, Ropers HH, Doerner C, Monaco A, Bergen AA, Lebo R, Warburg M, et al (1992) Isolation of a candidate gene for Norrie disease by positional cloning. Nat Genet 1:199–203

    CAS  PubMed  Google Scholar 

  228. Berger W, Meindl A, van de Pol TJ, Cremers FP, Ropers HH, Doerner C, Monaco A, Bergen AA, Lebo R, Warburg M, et al (1992) Erratum: isolation of a candidate gene for Norrie disease by positional cloning. Nat Genet 2:84

    CAS  PubMed  Google Scholar 

  229. Chen ZY, Hendriks RW, Jobling MA, Powell JF, Breakefield XO, Sims KB, Craig IW (1992) Isolation and characterization of a candidate gene for Norrie disease. Nat Genet 1:204–208

    CAS  PubMed  Google Scholar 

  230. Berger W, van de Pol D, Bachner D, Oerlemans F, Winkens H, Hameister H, Wieringa B, Hendriks W, Ropers HH (1996) An animal model for Norrie disease (ND): gene targeting of the mouse ND gene. Hum Mol Genet 5:51–59

    Article  CAS  PubMed  Google Scholar 

  231. Parkinson J (1817) An essay on the shaking palsy. Sherwood, Neely & Jones, London

  232. Nussbaum RL, Polymeropoulos MH (1997) Genetics of Parkinson’s disease. Hum Mol Genet 6:1687–1691

    Article  CAS  PubMed  Google Scholar 

  233. Warner TT, Schapira AH (2003) Genetic and environmental factors in the cause of Parkinson’s disease. Ann Neurol 53 [Suppl 3]:S16–S23

    Google Scholar 

  234. Chung KK, Dawson VL, Dawson TM (2003) New insights into Parkinson’s disease. J Neurol 250 [Suppl 3]:III15–III24

    Google Scholar 

  235. Gowers WR (1900) A manual of diseases of the nervous system, vol I. Blakiston’s Son, Philadelphia

  236. Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, et al (2001) Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA 286:2239–2244

    Article  CAS  PubMed  Google Scholar 

  237. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047

    CAS  PubMed  Google Scholar 

  238. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608

    CAS  PubMed  Google Scholar 

  239. Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, et al (2001) Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease. JAMA 286:2245–2250

    Article  CAS  PubMed  Google Scholar 

  240. Wu RM, Cheng CW, Chen KH, Lu SL, Shan DE, Ho YF, Chern HD (2001) The COMT L allele modifies the association between MAOB polymorphism and PD in Taiwanese. Neurology 56:375–382

    CAS  PubMed  Google Scholar 

  241. Mattila KM, Rinne JO, Lehtimaki T, Roytta M, Ahonen JP, Hurme M (2002) Association of an interleukin 1B gene polymorphism (-511) with Parkinson’s disease in Finnish patients. J Med Genet 39:400–402

    Article  CAS  PubMed  Google Scholar 

  242. Chan DK, Lam MK, Wong R, Hung WT, Wilcken DE (2003) Strong association between N-acetyltransferase 2 genotype and PD in Hong Kong Chinese. Neurology 60:1002–1005

    CAS  PubMed  Google Scholar 

  243. Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT, Trojanowski JQ, Lee VM (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300:636–640

    Article  CAS  PubMed  Google Scholar 

  244. Shoffner JM, Watts RL, Juncos JL, Torroni A, Wallace DC (1991) Mitochondrial oxidative phosphorylation defects in Parkinson’s disease. Ann Neurol 30:332–339

    CAS  PubMed  Google Scholar 

  245. Parker WD Jr, Swerdlow RH (1998) Mitochondrial dysfunction in idiopathic Parkinson disease. Am J Hum Genet 62:758–762

    Google Scholar 

  246. Walt JM van der, Nicodemus KK, Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Haines JL, Koller WC, Lyons K, et al (2003) Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 72:804–811

    Article  PubMed  Google Scholar 

  247. Sandyk R (1993) The relationship between diabetes mellitus and Parkinson’s disease. Int J Neurosci 69:125–130

    CAS  PubMed  Google Scholar 

  248. Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34:521–533

    CAS  PubMed  Google Scholar 

  249. Down JLH (1887) Mental affections of childhood and youth. Churchill, London

  250. Prader AL A, Willi H (1956) Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach myatonieartigem Zustand im Neugeborenenalter. Schweiz Med Wochenschr 86:1260–1261

    Google Scholar 

  251. DelParigi A, Tschöp M, Heiman ML, Salbe AD, Vozarova B, Sell SM, Bunt JC, Tataranni PA (2002) High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome. J Clin Endocrinol Metab 87:5461–5464

    Article  CAS  PubMed  Google Scholar 

  252. Tschöp M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407:908–913

    CAS  PubMed  Google Scholar 

  253. Butler JV, Whittington JE, Holland AJ, Boer H, Clarke D, Webb T (2002) Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study. Dev Med Child Neurol 44:248–255

    Article  CAS  PubMed  Google Scholar 

  254. Hoybye C, Hilding A, Jacobsson H, Thoren M (2002) Metabolic profile and body composition in adults with Prader-Willi syndrome and severe obesity. J Clin Endocrinol Metab 87:3590–3597

    Article  CAS  PubMed  Google Scholar 

  255. Forssman H, Hagberg B (1964) Prader-Willi syndrome in boy of ten with prediabetes. Acta Paediatr 53:70–78

    CAS  PubMed  Google Scholar 

  256. Sills IN, Rapaport R (1998) Non-insulin dependent diabetes mellitus in a prepubertal child with Prader-Willi syndrome. J Pediatr Endocrinol Metab 11:281–282

    CAS  PubMed  Google Scholar 

  257. Schuster DP, Osei K, Zipf WB (1996) Characterization of alterations in glucose and insulin metabolism in Prader-Willi subjects. Metabolism 45:1514–1520

    CAS  PubMed  Google Scholar 

  258. Yang T, Adamson TE, Resnick JL, Leff S, Wevrick R, Francke U, Jenkins NA, Copeland NG, Brannan CI (1998) A mouse model for Prader-Willi syndrome imprinting-centre mutations. Nat Genet 19:25–31

    CAS  PubMed  Google Scholar 

  259. Porter FS, Rogers LE, Sidbury JB Jr (1969) Thiamine-responsive megaloblastic anemia. J Pediatr 74:494–504

    PubMed  Google Scholar 

  260. Viana MB, Carvalho RI (1978) Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: a new syndrome? J Pediatr 93:235–238

    CAS  PubMed  Google Scholar 

  261. Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, Szargel R, McDonald L, Shalata A, Nosaka K, et al (1999) Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nat Genet 22:300–304

    Article  CAS  PubMed  Google Scholar 

  262. Tulp N (1739) Observationes Medicae. Wishoff, Leyden

  263. Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, Meitinger T, Jaksch M (2000) A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. J Med Genet 37:669–673

    PubMed  Google Scholar 

  264. Oishi K, Hofmann S, Diaz GA, Brown T, Manwani D, Ng L, Young R, Vlassara H, Ioannou YA, Forrest D, et al (2002) Targeted disruption of Slc19a2, the gene encoding the high-affinity thiamin transporter Thtr-1, causes diabetes mellitus, sensorineural deafness and megaloblastosis in mice. Hum Mol Genet 11:2951–2960

    Article  CAS  PubMed  Google Scholar 

  265. Fleming JC, Tartaglini E, Kawatsuji R, Yao D, Fujiwara Y, Bednarski JJ, Fleming MD, Neufeld EJ (2003) Male infertility and thiamine-dependent erythroid hypoplasia in mice lacking thiamine transporter Slc19a2. Mol Genet Metab 80:234–241

    Article  CAS  PubMed  Google Scholar 

  266. Nakano KK, Dawson DM, Spence A (1972) Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology 22:49–55

    CAS  PubMed  Google Scholar 

  267. Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, et al (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228

    CAS  PubMed  Google Scholar 

  268. Schöls L, Amoiridis G, Langkafel M, Buttner T, Przuntek H, Riess O, Vieira-Saecker AM, Epplen JT (1995) Machado-Joseph disease mutations as the genetic basis of most spinocerebellar ataxias in Germany. J Neurol Neurosurg Psychiatry 59:449–450

    PubMed  Google Scholar 

  269. Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A (1996) Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nat Genet 13:196–202

    CAS  PubMed  Google Scholar 

  270. Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 15:62–69

    CAS  PubMed  Google Scholar 

  271. Takiyama YSK, Namekawa M, Soutome M, Esumi E, Ogawa T, Ishikawa K, Mizusawa H, Nakano I, Nishizawa M (1998) A Japanese family with spinocerebellar ataxia type 6 which includes three individuals homozygous for an expanded CAG repeat in the SCA6/CACNL1A4 gene. J Neurol Sci 158:141–147

    Article  CAS  PubMed  Google Scholar 

  272. Morgagni GB (1768) Epistola anatomica medica

  273. Shereshevskii NA (1925) In relation to the question of a connection between congenital abnormalities and endocrinopathies. Russian Endocrinological Society

  274. Ullrich O (1930) Über typische Kombinationsbilder multipler Abartungen. Z Kinderheilkd 49:271

    Google Scholar 

  275. Turner HH (1938) A syndrome of infantilism, congenital webbed neck, and cubitus valgus. Endocrinology 23:566–574

    Google Scholar 

  276. Hortling H, Delachapelle A, Frisk M, Widholm O (1964) The syndromes of obesity and of delayed growth in adolescence. Acta Med Scand 175 [Suppl 412]:109–117

  277. AvRuskin TW, Crigler JF Jr, Soeldner JS (1979) Turner’s syndrome and carbohydrate metabolism. I. Impaired insulin secretion after tolbutamide and glucagon stimulation tests: evidence of insulin deficiency. Am J Med Sci 277:145–152

    CAS  PubMed  Google Scholar 

  278. Jackson IM, Buchanan KD, McKiddie MT, Prentice CR (1966) Carbohydrate metabolism and pituitary function in gonadal dysgenesis (Turner’s syndrome). J Endocrinol 34:289–298

    CAS  PubMed  Google Scholar 

  279. Nielsen J, Johansen K, Yde H (1969) The frequency of diabetes mellitus in patients with Turner’s syndrome and pure gonadal dysgenesis. Blood glucose, plasma insulin and growth hormone level during an oral glucose tolerance test. Acta Endocrinol (Copenh) 62:251–269

    Google Scholar 

  280. Reichel W, Garcia-Bunuel R, Dilallo J (1971) Progeria and Werner’s syndrome as models for the study of normal human aging. J Am Geriatr Soc 19:369–375

    CAS  PubMed  Google Scholar 

  281. Martin GM (1997) The Werner mutation: does it lead to a “public” or “private” mechanism of aging? Mol Med 3:356–358

    CAS  PubMed  Google Scholar 

  282. Kakigi R, Endo C, Neshige R, Kohno H, Kuroda Y (1992) Accelerated aging of the brain in Werner’s syndrome. Neurology 42:922–924

    CAS  PubMed  Google Scholar 

  283. Umehara F, Abe M, Nakagawa M, Izumo S, Arimura K, Matsumuro K, Osame M (1993) Werner’s syndrome associated with spastic paraparesis and peripheral neuropathy. Neurology 43:1252–1254

    CAS  PubMed  Google Scholar 

  284. Just A, Canaple S, Joly H, Piussan C, Rosa A (1996) Complications neurologiques dans un cas de syndrome de Werner. Rev Neurol (Paris) 152:634–636

    Google Scholar 

  285. Malandrini A, Dotti MT, Villanova M, Battisti C, Federico A (2000) Neurological involvement in Werner’s syndrome: clinical and biopsy study of a familial case. Eur Neurol 44:187–189

    Article  CAS  PubMed  Google Scholar 

  286. Zackai AH, Weber D, Noth R (1974) Cardiac findings in Werner’s syndrome. Geriatrics 29:141–148

    CAS  Google Scholar 

  287. Tri TB, Combs DT (1978) Congestive cardiomyopathy in Werner’s syndrome. Lancet I:1052–1053

    Article  Google Scholar 

  288. Alberti KG, Young JD, Hockaday TD (1974) Werner’s syndrome: metabolic observations. Proc R Soc Med 67:36–38

    CAS  PubMed  Google Scholar 

  289. Yamada K, Ikegami H, Yoneda H, Miki T, Ogihara T (1999) All patients with Werner’s syndrome are insulin resistant, but only those who also have impaired insulin secretion develop overt diabetes. Diabetes Care 22:2094–2095

    Google Scholar 

  290. Izumino K, Sakamaki H, Ishibashi M, Takino H, Yamasaki H, Yamaguchi Y, Chikuba N, Matsumoto K, Akazawa S, Tokuyama K, et al (1997) Troglitazone ameliorates insulin resistance in patients with Werner’s syndrome. J Clin Endocrinol Metab 82:2391–2395

    Article  CAS  PubMed  Google Scholar 

  291. Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, et al (1996) Positional cloning of the Werner’s syndrome gene. Science 272:258–262

    CAS  PubMed  Google Scholar 

  292. Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, et al (2003) LMNA mutations in atypical Werner’s syndrome. Lancet 362:440–445

    Article  CAS  PubMed  Google Scholar 

  293. Shackleton S, Lloyd DJ, Jackson SN, Evans R, Niermeijer MF, Singh BM, Schmidt H, Brabant G, Kumar S, Durrington PN, et al (2000) LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet 24:153–156

    Article  CAS  PubMed  Google Scholar 

  294. Speckman RA, Garg A, Du F, Bennett L, Veile R, Arioglu E, Taylor SI, Lovett M, Bowcock AM (2000) Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C. Am J Hum Genet 66:1192–1198

    Article  CAS  PubMed  Google Scholar 

  295. Garg A (2004) Acquired and inherited lipodystrophies. N Engl J Med 350:1220–1234

    Article  CAS  PubMed  Google Scholar 

  296. Hegele RA, Cao H, Harris SB, Zinman B, Hanley AJ, Anderson CM (2000) Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians. Physiol Genomics 3:39–44

    CAS  PubMed  Google Scholar 

  297. Hegele RA, Cao H, Huff MW, Anderson CM (2000) LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration. J Clin Endocrinol Metab 85:3089–3093

    Article  CAS  PubMed  Google Scholar 

  298. Lombard DB, Beard C, Johnson B, Marciniak RA, Dausman J, Bronson R, Buhlmann JE, Lipman R, Curry R, Sharpe A, et al (2000) Mutations in the WRN gene in mice accelerate mortality in a p53-null background. Mol Cell Biol 20:3286–3291

    Article  CAS  PubMed  Google Scholar 

  299. Wolfram DJ, Wagener HP (1938) Diabetes mellitus and simple optic atrophy among siblings: report of four cases. Mayo Clin Proc 13:715–718

    Google Scholar 

  300. Swift RG, Perkins DO, Chase CL, Sadler DB, Swift M (1991) Psychiatric disorders in 36 families with Wolfram syndrome. Am J Psychiatry 148:775–779

    CAS  PubMed  Google Scholar 

  301. Swift RG, Polymeropoulos MH, Torres R, Swift M (1998) Predisposition of Wolfram syndrome heterozygotes to psychiatric illness. Mol Psychiatry 3:86–91

    Article  CAS  PubMed  Google Scholar 

  302. Furlong RA, Ho LW, Rubinsztein JS, Michael A, Walsh C, Paykel ES, Rubinsztein DC (1999) A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases. Neurosci Lett 277:123–126

    Article  CAS  PubMed  Google Scholar 

  303. Bezold R, Jaksch M, Kaufhold P, Gerbitz KD (1995) DIDMOAD or Wolfram syndrome. A mitochondrial-mediated disorder. Diabetes Care 18:583–584

    Google Scholar 

  304. Bezold R, Jaksch M, Kaufhold P, Obermaier-Kusser B, Gerbitz KD (1997) Analysis of the mitochondrial DNA from patients with Wolfram (DIDMOAD) syndrome. Mol Cell Biochem 174:209–213

    Article  PubMed  Google Scholar 

  305. Inoue HT, Tanizawa Y, Wasson J, Behn P. Kalidas K, Bernal-Mizrachi E, Meuckler M, Marshall H, Donis-Keller H, Crock P, Rogers D, Mikuni M, Kumashiro H, Higashi K, Sobue G, Oka Y, Permutt MA (1998) A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet:143–148

    Google Scholar 

  306. Strom TM, Hortnagel K, Gekeler F, Scharfe C, Rabl W, Gerbitz KD, Meitinger T (1998) Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum Mol Genet 7:2021–2028

    CAS  PubMed  Google Scholar 

  307. Osman AA, Saito M, Makepeace C, Permutt MA, Schlesinger P, Mueckler M (2003) Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium. J Biol Chem 278:52755–52762

    Article  CAS  PubMed  Google Scholar 

  308. Woodhouse NJ, Sakati NA (1983) A syndrome of hypogonadism, alopecia, diabetes mellitus, mental retardation, deafness, and ECG abnormalities. J Med Genet 20:216–219

    CAS  PubMed  Google Scholar 

  309. Gul D, Ozata M, Mergen H, Odabasi Z, Mergen M (2000) Woodhouse and Sakati syndrome (MIM 241080): report of a new patient. Clin Dysmorphol 9:123–125

    CAS  PubMed  Google Scholar 

  310. Ristow M, Vorgerd M, Mohlig M, Schatz H, Pfeiffer A (1997) Deficiency of phosphofructo-1-kinase/muscle subtype in humans impairs insulin secretion and causes insulin resistance. J Clin Invest 100:2833–2841

    CAS  PubMed  Google Scholar 

  311. Silva JP, Kohler M, Graff C, Oldfors A, Magnuson MA, Berggren PO, Larsson NG (2000) Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat Genet 26:336–340

    Article  CAS  PubMed  Google Scholar 

  312. Winegrad AI (1972) Diabetic neuropathy. N Engl J Med 286:1261–1262

    CAS  PubMed  Google Scholar 

  313. Harati Y (1996) Diabetes and the nervous system. Endocrinol Metab Clin North Am 25:325–359

    CAS  PubMed  Google Scholar 

  314. Vinik AI, Park TS, Stansberry KB, Pittenger GL (2000) Diabetic neuropathies. Diabetologia 43:957–973

    Google Scholar 

  315. Enersen OD (2004) Whonamedit.com. Oslo (http://www.whonamedit.com)

Download references

Acknowledgements

The author thanks J.-C. von Kleist-Retzow, S.A. Shoichet, M. Vorgerd, and anonymous reviewers for critical comments on the manuscript, A. Duverger for help with French references, and R. Heidmann and D. Kollhof for excellent librarian support. The remarkable resources of http://www.Whonamedit.com regarding the historical contextualization of several syndromes are gratefully acknowledged [315]. The author is currently supported by Deutsche Diabetes Gesellschaft, Deutsche Forschungsgemeinschaft, Fritz-Thyssen-Stiftung, Wilhelm-Sander-Stiftung, and Wissenschaftsgemeinschaft Gottfried Wilhelm Leibniz/Leibniz-Gemeinschaft.

Author information

Authors and Affiliations

  1. Department of Clinical Nutrition, German Institute for Human Nutrition, Potsdam-Rehbrücke, 114 Arthur-Scheunert-Allee, 14558, Nuthetal-Berlin, Germany

    Michael Ristow

  2. Department of Endocrinology, Diabetes, and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany

    Michael Ristow

Authors
  1. Michael Ristow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Ristow.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ristow, M. Neurodegenerative disorders associated with diabetes mellitus. J Mol Med 82, 510–529 (2004). https://doi.org/10.1007/s00109-004-0552-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-004-0552-1

Keywords

Search

Navigation