Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)]

J Clin Endocrinol Metab. 2000 Nov;85(11):4354-8. doi: 10.1210/jcem.85.11.6981.


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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Animals
  • Apolipoproteins E / genetics*
  • Binding Sites
  • Exons
  • Humans
  • Hypertriglyceridemia / complications*
  • Hypertriglyceridemia / genetics
  • Leucine
  • Lipoproteins / blood*
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Male
  • Middle Aged
  • Postoperative Complications
  • Rabbits
  • Receptors, Lipoprotein / metabolism
  • Sequence Deletion*
  • Spleen / pathology*
  • Splenectomy
  • Splenomegaly / genetics*
  • Splenomegaly / pathology
  • Splenomegaly / surgery
  • Triglycerides / blood


  • Apolipoproteins E
  • Lipoproteins
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Receptors, Lipoprotein
  • Triglycerides
  • Alanine Transaminase
  • Leucine