Primary
hypobetalipoproteinemia (pHBL) is characterized by plasma
cholesterol levels <5th percentile of a population distribution. Plasma non-
cholesterol sterols (NCS) are markers of
cholesterol liver synthesis and intestinal absorption. Plasma NCS were measured in 111 pHBL subjects, 108 low
cholesterol (LC) and 253 normal
cholesterol (NC) controls to gain information on
cholesterol metabolism in pHBL, and to assess whether NCS measurements may aid in distinguishing pHBL from LC controls. pHBL subjects compared with LC controls were characterized by increased
cholesterol absorption (
campesterol/TC) while the synthesis (
lathosterol/TC) was not increased. The analysis of pHBL subjects divided by gene defect showed a high
campesterol/TC ratio in familial HBL (FHBL) carriers of apolipoproteinB (
ApoB) truncations longer than
ApoB48 and in FHBL without known gene defect ("not linked"). One not linked kindred was characterized by an increase of the 7-dehydrocholesterol/latho ratio. In a discriminant analysis plasma NCS did not improve the power of TC levels to distinguish FHBL from LC controls. In conclusion, increased
cholesterol absorption was found in FHBL subjects harbouring truncations of
ApoB>
ApoB48, and FHBL harbouring as yet unknown molecular defects. Not linked FHBL kindred are not homogeneous in terms of plasma NCS levels. NCS cannot replace genetic HBL analysis.