Homozygous hypobetalipoproteinemia with spared chylomicron formation.

Thirteen members of a family carrying a gene for pedigree of hypobetalipoproteinemia were analyzed for lipoprotein compositions, apolipoprotein (apo) B levels, and apo B isoforms. Judging from low density lipoprotein (LDL)-cholesterol (Chol) and apo B levels, a 75-year-old proband, a father who died of unknown fever, thrombopenia, and anemia, and his wife were heterozygous for hypobetalipoproteinemia. The proband had ataxic movement of hands and gait disturbance in later life. Three of four living siblings had extremely low levels of LDL-Chol (6 mg/dL) and LDL-apo B (2 mg/dL), and were postulated to have homozygous hypobetalipoproteinemia. Electrophoresis revealed marked deficiency of apo B-100, although trace amounts were noted in LDL. In contrast, apo B-48 was present in chylomicrons obtained after a fatty meal in the two patients with homozygous hypobetalipoproteinemia, indicating a selective deficiency of apo B-100 but not apo B-48. The defect in these patients seemingly is different from abnormal apo B-37 reported recently for a family with hypobetalipoproteinemia. Clinically, acanthocytotic red blood cells (8% to 12%), fatty liver, and low levels of serum lipid-soluble vitamins A and D were noted in homozygotes. One heterozygous sibling had 26 mg/dL LDL-Chol and 5 mg/dL LDL-apo B levels. All seven subjects in the third generation had low levels of Chol (85 to 140 mg/dL), LDL-Chol (40 to 63 mg/dL) and LDL-apo B (10 to 20 mg/dL). They also showed mild acanthocytosis (0.5% to 2%) and a decrease of fat-soluble vitamins in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)