Familial splenomegaly : Macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (Δ149 Leu)]

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 11; pp. 4354 - 4358
• Main Authors: NGUYEN, T. U. T, KRUCKEBERG, Kent E, O'BRIEN, John F, JI, Zhong-Sheng, KARNES, Pamela S, CROTTY, Thomas B, HAY, Ian D, MAHLEY, Robert W, O'BRIEN, Timothy
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.11.2000
• Subjects: Adult; Alanine Transaminase - blood; Animals; Apolipoproteins E - genetics; Binding Sites; Biological and medical sciences; Disorders of blood lipids. Hyperlipoproteinemia; Exons; Hematologic and hematopoietic diseases; Humans; Hypertriglyceridemia - complications; Hypertriglyceridemia - genetics; Leucine; Lipoproteins - blood; Low Density Lipoprotein Receptor-Related Protein-1; Male; Medical sciences; Metabolic diseases; Middle Aged; Other diseases. Hematologic involvement in other diseases; Postoperative Complications; Rabbits; Receptors, Lipoprotein - metabolism; Sequence Deletion; Spleen - pathology; Splenectomy; Splenomegaly - genetics; Splenomegaly - pathology; Splenomegaly - surgery; Triglycerides - blood; Human; Splenomegaly; Metabolic diseases; Lipids; Hyperlipoproteinemia; Hemopathy; Histiocytosis; Enzymopathy; Genetic determinism; Splenectomy; Concomitant disease; Apolipoprotein E; Hypertriglyceridemia; Surgery; Adult; Evolution; Mutation; Dyslipemia
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.11.4354

Splenomegaly with sea-blue histiocytes is not associated with dyslipidemia, except in severe cases of hypertriglyceridemia, Tangier disease, or lecithin cholesterol acyltransferase deficiency. We describe two kindreds in which the sea-blue histiocyte syndrome was associated with an apoE variant in the absence of severe dyslipidemia. Both patients presented with mild hypertriglyceridemia and splenomegaly. After splenectomy both patients developed severe hypertriglyceridemia. Pathological evaluation of the spleen revealed the presence of sea-blue histiocytes. A mutation of apoE was demonstrated, with a 3-bp deletion resulting in the loss of a leucine at position 149 in the receptor-binding region of the apoE molecule [apoE (delta149 Leu)]. Although both probands were unrelated, they were of French Canadian ancestry, suggesting the possibility of a founder effect. In summary, we describe two unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. In addition, we provide evidence linking the syndrome to an inherited dominant mutation in the apoE gene, a 3-bp deletion on the background of an apoE 3 allele that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia.