Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and familial combined hypolipidemia

Background The most frequent monogenic causes of low plasma cholesterol are familial hypobetalipoproteinemia (FHBL1) because of truncating mutations in apolipoprotein B coding gene (APOB) and familial combined hypolipidemia (FHBL2) due to loss-of-function mutations in ANGPTL3 gene. Objective A direct comparison of lipid phenotypes of these 2 conditions has never been carried out. In addition, although an increased prevalence of liver steatosis in FHBL1 has been consistently reported, the hepatic consequences of FHBL2 are not well established. Methods We investigated 350 subjects, 67 heterozygous carriers of APOB mutations, 63 carriers of the p.S17* mutation in ANGPTL3 (57 heterozygotes and 6 homozygotes), and 220 noncarrier normolipemic controls. Prevalence and degree of hepatic steatosis were assessed by ultrasonography. Results A steady decrease of low-density lipoprotein cholesterol levels were observed from heterozygous to homozygous FHBL2 and to FHBL1 individuals, with the lowest levels in heterozygous FHBL1 carrying truncating mutations in exons 1 to 25 of APOB (P for trend