Familial defective apolipoprotein B-100 (FDB) is a genetic disorder caused
by a substitution of glutamine for arginine at residue 3500 of the apolipop
rotein B-100 molecule. We have identified 23 heterozygotes and one homozygo
te for FDB (frequency 1:20) in a group of 510 patients with hypercholestero
lemia. Mean age of the patients (18 females and 6 males) was 46 years. The
diagnosis of FDB was based on point mutation PCR analysis of exon 26 of the
apo B gene. Plasma lipids in heterozygous patients were: total cholesterol
8.76+/-1.2 mmol/l, triglycerides 1.42+/-0.5 mmol/l, HDL-cholesterol 1.43+/
-0.3 mmol/l, LDL-cholesterol 6.69+/-1.2 mmol/l, apoB 1.69+/-0.4 g/l, Lp(a)
0.26+/-0.2 g/l. The most frequent apoE genotype was 3/3 (19 patients), apoE
3/4 genotype was found in 3 patients and one person had apoE 2/3. Xanthela
sma palpebrarum was present in 4 patients and tendon xanthomas in 3 patient
s including the homozygote. Premature manifestation of coronary heart disea
se was revealed in 3 patients. Sixteen patients were treated with statins,
a combination of statin and resin was used in 2 patients (including the hom
ozygote), whereas six patients were treated with the diet only, We conclude
that although the plasma lipid levels of total and LDL cholesterol in FDB
patients are lower than in patients with familial hypercholesterolemia, the
patients with FDB suffer from premature atherosclerosis. The therapeutic a
pproach to FDB individuals and patients with familial hypercholesterolemia
is very similar.