Clinical Characterization of a Case with Familial Hypobetalipoproteinemia Caused by Apo B-76, a New Truncation of Apolipoprotein B, Combined with Apo E2/E2 Phenotype.

Abstract

Wereport a 43-year-old Japanese man with hypobetalipoproteinemia likely due to apolipoprotein (apo) B-76, a new truncation of apo B, and with homozygousity for the apo E2 isoform. He had no history suggestive of fat malabsorption and no sign of neurological disorder. His fasting baseline serum low-density lipoprotein (LDL) cholesterol and apo B levels were approximately half of normal. His plasma apo E level was elevated and its phenotype showed the E2/E2 homozygote. SDS-polyacrylamide gel electrophoresis of delipidated LDLfraction revealed a new truncated apo B, designated as apo B-76 according to the centile system of nomenclature. The postprandial lipid metabolism of the patient showedan almost normal response after fat loading. (Internal

Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk

“…Thus, these fi ndings support the anecdotal reports of intestinal manifestations suggestive of mild fat malabsorption in apoB100/apoB6.7 ( 126 ) and apoB100/B8.2 ( 127 ) individuals, when they refrained from their fat-restricted diet. By contrast, normal postprandial fat-absorption responses were found in heterozygous apoB48.4 and apoB76 FHBL subjects ( 128,129 ), implying that only those FHBL heterozygotes with apoBs shorter than apoB-48 have a reduced capacity to assemble dietary lipids into chylomicrons.…”

Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia

“…The APOB mutations causing FHBL are usually nonsense, splicing and frameshift mutations that cause the production of a truncated apoB. While case studies with apoB-48.4 and apoB-76 have shown 'normal' postprandial responses (5,6), heterozygous FHBL subjects with apoB truncations shorter than apoB-48, and therefore only a single fully-functional apoB-48 allele, have decreased TRL production, but normal postprandial TRL particle clearance (7).…”