Dietary fat clearance in type V hyperlipoproteinaemia secondary to a rare variant of human apolipoprotein E: the apolipoprotein E3 (Arg 136 -> Ser)

This present case report describes two siblings with severe type V hyperlip oproteinaemia, diagnosed very early in life and due to the combination of t he common apolipoprotein (Apo) E2 allele and a rare mutant variant of ApoE, ApoE3 (Arg 136 --> Ser). Phenotyping of ApoE falsely identified E2/E2 phen otype. The presence of mutated ApoE was suspected on an unusual restriction polymorphism of a Hha 1 restriction site and confirmed by sequence analysi s of the cloned polymerase chain reaction fragment of exon 4 and familial s egregation study. The severity of the hypertriacylglycerolaemia was modulat ed by the lipid content of the diet. A low-fat diet enriched in medium-chai n triacylglycerol (TAG) decreased but did not normalize plasma TAG levels i n both affected patients of the pedigree. A standardized lipid-enriched tes t meal showed a marked impairment of TAG-rich lipoprotein (TRL) clearance, especially the exogeneous TRL bearing ApoB-48 which still represented 79% o f total TRL 7 h after the fat load. Finally, differences between the male a nd female siblings with the existence of a consanguine relationship in thei r parents suggested the involvement of other genetic factors in modulating the severity of phenotypic expression. This observation reinforces the usef ulness of genotyping of ApoE for the characterization of genetic hypertriac ylglycerolaemia and selection of the appropriate diet and treatment.