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.