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)