Severe xanthomatosis associated with familial apolipoprotein E deficiency.

AIM To present the clinical, dermatological, and histological features of a patient with generalised xanthomatosis, familial apolipoprotein (apo) E deficiency, and unusual type III hyperlipoproteinaemia (HLP). METHODS The underlying molecular defect was disclosed using molecular biological techniques. The unusual xanthomas were histologically analysed and the morphology of the abnormal lipoprotein particles examined using electron microscopy. RESULTS A 10 base pair deletion in exon 4 of the proband's apo epsilon gene (base pairs 4037-4046 coding for amino acids 209-212 of the mature protein) was identified. This is predictive for a reading frameshift encoding a premature stop (TGA) in codon 229. The mutation is responsible for delayed catabolism of atherogenic lipoprotein remnants, lipid storage in monocyte/macrophages, and phenotypic expression of xanthomatosis early in life. CONCLUSIONS Familial apo E deficiency is a rare genetic disease which offers the unique opportunity to study the impact of apo E on lipoprotein metabolism and development of atherosclerosis in humans.