Alternative titles; symbols
SNOMEDCT: 37821003; ORPHA: 158029; DO: 4423;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19q13.32 | Sea-blue histiocyte disease | 269600 | Autosomal recessive | 3 | APOE | 107741 |
A number sign (#) is used with this entry because primary sea-blue histiocytosis can be caused by mutation in the APOE gene (107741).
This disorder is characterized by splenomegaly, mild thrombocytopenia, and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The name was coined by Silverstein et al. (1970). Holland et al. (1965) suggested that the syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses. Jones et al. (1970) described an affected brother and sister. Parental consanguinity was possible because both parents came from the same restricted area of West Virginia. Lake et al. (1970) suggested that the 'sea-blue' designation be abandoned because the marrow contains a second variety of abnormal cell which never stains 'sea-blue' and because they had observed a 'malignant' disorder with 'sea-blue' cells and progressive neurologic disease characterized by ataxia, dementia, and seizures. Heterozygotes may have some sea-blue histiocytes in the bone marrow (Zlotnick and Fried, 1970).
Wewalka (1970) gave a long-term follow-up on a case reported in 1950. He commented on eye changes: a white ring surrounding the macula. Berman (1972) described 2 sisters with this disorder in whom the initial diagnosis was Gaucher disease. The qualitative test for excessive mucopolysacchariduria was mildly positive in these patients. Sawitsky et al. (1972) added 2 families. In one, 4 brothers and a sister out of 7 sibs with normal parents were affected. The family was from Trinidad. In the second, an American black family, mother and daughter were affected. The authors concluded that this disorder is a lipidosis. They presented a pedigree of the family of Zlotnick and Fried (1970). The parents were first cousins in their Iranian Jewish family and showed changes consistent with carrier status.
Sea-blue histiocytes have been observed in Norum disease (245900) (Jacobsen et al., 1972) and in Niemann-Pick disease type C1 (257220). Chainuvati et al. (1977) described the disease in a Thai brother and sister. The abnormal histiocytes were found in bone marrow and liver. Cirrhosis and absence of axillary hair were found in both.
Blankenship et al. (1973) suggested the existence of a dominant variety, which they called the Lewis type for the name of the family. Three sibs had splenomegaly, peripheral neuropathy, cafe-au-lait spots and elevated serum acid phosphatase levels. The father, who was not known to be related to the mother, showed elevated bone marrow acid phosphatase and abnormal histiocytes. The Lewis type of Blankenship et al. (1973) subsequently was shown to be a form of Niemann-Pick disease (607616). The findings in the father represented, presumably, heterozygote manifestation.
A presumably dominant but different form of sea-blue histiocyte disease was described by Swaiman et al. (1975), who found ceroid-lipofuscin storage and varied neurologic changes, especially posterior column degeneration, often beginning in the teens. Gait disturbance, positive Romberg and Babinski tests, and diminished vibratory and position senses were described.
Zina and Bundino (1983) reported an affected brother and sister. The brother, aged 25 years, had skin lesions that contained sea-blue histiocytes. Like her brother, the sister, aged 17 years, had hepatosplenomegaly and pulmonary infiltrates; sea-blue histiocytes were demonstrated in muscles and subcutaneous tissue. Viana et al. (1990) reported sea-blue histiocytosis as a feature of 4 sibs in a Brazilian kindred with nonneuropathic (presumably type B) Niemann-Pick disease.
Nguyen et al. (2000) described 2 unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. They provided evidence linking the syndrome to an inherited dominant APOE mutation (delta149 leu; 107741.0031) that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia.
In 2 brothers with splenomegaly, thrombocytopenia, and hypertriglyceridemia, Faivre et al. (2005) identified the delta149 leu mutation in the APOE gene. Their mother, who also had the mutation, had only isolated hypertriglyceridemia. One brother had a large beta band in the VLDL fraction and an elevated VLDL cholesterol-to-plasma triglyceride ratio; Faivre et al. (2005) suggested that the more severe phenotype might be explained by the presence of an APOE2 allele (107741.0001) in this patient.
Berman, E. R. Personal Communication. Jerusalem, Israel 1972.
Blankenship, R. M., Greenburg, B. R., Lucas, R. N., Reynolds, R. D., Beutler, E. Familial sea-blue histiocytes with acid phosphatasemia: a syndrome resembling Gaucher disease: the Lewis variant. JAMA 225: 54-56, 1973. [PubMed: 4123476]
Chainuvati, T., Piankijagum, A., Viranuvatti, V., Silverstein, M. N. Sea-blue histiocyte syndrome in Thai siblings. Acta Haemat. 58: 58-64, 1977. [PubMed: 410219] [Full Text: https://doi.org/10.1159/000207807]
Faivre, L., Saugier-Veber, P., Pais de Barros, J.-P., Verges, B., Couret, B., Lorcerie, B., Thauvin, C., Charbonnier, F., Huet, F., Gambert, P., Frebourg, T., Duvillard, L. Variable expressivity of the clinical and biochemical phenotype associated with the apolipoprotein E p.Leu149del mutation. Europ. J. Hum. Genet. 13: 1186-1191, 2005. [PubMed: 16094309] [Full Text: https://doi.org/10.1038/sj.ejhg.5201480]
Fried, K., Beer, S., Drespin, H. I., Leiba, H., Djaldetti, M., Zitman, D., Klibansky, C. Biochemical, genetic and ultrastructural study of a family with the sea-blue histiocyte syndrome--chronic non-neuronopathic Niemann-Pick disease. Europ. J. Clin. Invest. 8: 249-253, 1978. [PubMed: 100330] [Full Text: https://doi.org/10.1111/j.1365-2362.1978.tb00860.x]
Holland, P., Hug, G., Schubert, W. K. Chronic reticuloendothelial cell storage disease. Am. J. Dis. Child. 110: 117-124, 1965. [PubMed: 14320759] [Full Text: https://doi.org/10.1001/archpedi.1965.02090030127002]
Jacobsen, C. D., Gjone, E., Hovig, T. Sea-blue histiocytes in familial lecithin cholesterol acyltransferase deficiency. Scand. J. Haemat. 9: 106-113, 1972. [PubMed: 4114809] [Full Text: https://doi.org/10.1111/j.1600-0609.1972.tb00918.x]
Jones, B., Gilbert, E. F., Zugibe, F. T., Thompson, H. Sea-blue histiocyte disease in siblings. Lancet 296: 73-75, 1970. Note: Originally Volume II.
Lake, B. D., Stephens, R., Neville, B. G. R. Syndrome of the sea-blue histiocyte. (Letter) Lancet 296: 309 only, 1970. Note: Originally Volume II. [PubMed: 4194379]
Nguyen, T. T., Kruckeberg, K. E., O'Brien, J. F., Ji, Z.-S., Karnes, P.S., Crottgy, T. B., Hay, I. D., Mahley, R. W., O'Brien, T. Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 leu)]. J. Clin. Endocr. Metab. 85: 4354-4358, 2000. [PubMed: 11095479] [Full Text: https://doi.org/10.1210/jcem.85.11.6981]
Sawitsky, A., Rosner, F., Chodsky, S. The sea-blue histiocyte syndrome, a review: genetic and biochemical studies. Semin. Hemat. 9: 285-297, 1972. [PubMed: 4114368]
Silverstein, M. N., Ellefson, R. D., Ahern, E. J. The syndrome of the sea-blue histiocyte. New Eng. J. Med. 282: 1-4, 1970. [PubMed: 4242937] [Full Text: https://doi.org/10.1056/NEJM197001012820101]
Silverstein, M. N., Ellefson, R. D. The syndrome of the sea-blue histiocyte. Semin. Hemat. 9: 293-307, 1972. [PubMed: 4114369]
Swaiman, K. F., Garg, B. P., Lockman, L. A. Sea-blue histiocyte and posterior column dysfunction: a familial disorder. Neurology 25: 1084-1085, 1975. [PubMed: 1237827] [Full Text: https://doi.org/10.1212/wnl.25.11.1084]
Tachibana, F., Hakozaki, H., Takahashi, K., Kojima, M., Enomoto, S., Wada, J. Syndrome of the sea-blue histiocyte: the first case report in Japan and review of the literature. Acta Path. Jpn. 29: 73-97, 1979.
Viana, M. B., Giugliani, R., Leite, V. H. R., Barth, M. L., Lekhwani, C., Slade, C. M., Fensom, A. Very low levels of high density lipoprotein cholesterol in four sibs of a family with non-neuropathic Niemann-Pick disease and sea-blue histiocytosis. J. Med. Genet. 27: 499-504, 1990. [PubMed: 2120445] [Full Text: https://doi.org/10.1136/jmg.27.8.499]
Wewalka, F. G. Syndrome of the sea-blue histiocyte. (Letter) Lancet 296: 1248 only, 1970. Note: Originally Volume II. [PubMed: 4098670] [Full Text: https://doi.org/10.1016/s0140-6736(70)92201-4]
Zina, A. M., Bundino, S. Familial sea-blue histiocytosis with cutaneous involvement: a case report with ultrastructural findings. Brit. J. Derm. 108: 355-361, 1983. [PubMed: 6299321] [Full Text: https://doi.org/10.1111/j.1365-2133.1983.tb03975.x]
Zlotnick, A., Fried, K. Sea-blue-histiocyte syndrome. (Letter) Lancet 296: 776 only, 1970. Note: Originally Volume II. [PubMed: 4195998] [Full Text: https://doi.org/10.1016/s0140-6736(70)90254-0]