Dysbetalipoproteinaemia--clinical and pathophysiological features

Dysbetalipoproteinaemia (type III hyperlipidaemia, broad-beta disease) is a highly atherogenic genetic disorder of lipoprotein metabolism. It presents with a severe mixed hyperlipidaemia in which the ratio of total cholesterol to triglycerides is typically 2:1. There is a high incidence of atherosclerotic complications and severe hypertriglyceridaemia may cause pancreatitis. Highly effective therapy is available and affected families also benefit from genetic counselling. We present a review of our experience with dysbetalipoproteinaemia at the lipid clinic of Groote Schuur Hospital to enhance awareness of this serious condition, for which the index of suspicion should be raised.

Retrospective review of case records, 1969-2001.

Lipid clinic of Groote Schuur Hospital, Cape Town.

Patients with dysbetalipoproteinaemia diagnosed by the presence of cholesterol-enriched very-low-density lipoproteins (VLDL) and/or dyslipidaemia associated with homozygosity for apolipoprotein E2 or carriers of the apoE2 (Arg145-->Cys) mutation.

One hundred and five patients were identified, 55 of whom were male and 50 female. The age at presentation was 48.8 +/- 11.1 years (mean, standard deviation). Total cholesterol was 12.0 +/- 5.5 mmol/l and plasma triglycerides 8.3 +/- 9.8 mmol/l. The ratio (by mass) of cholesterol to triglycerides within VLDL was 0.52 +/- 0.17, while VLDL cholesterol to plasma triglycerides was 0.33 +/- 0.09. Fifty patients were epsilon 2 homozygotes while 22 carried the apoE2 (Arg145-->Cys) mutation. Palmar crease xanthomas occurred in 20% of patients, cutaneous xanthomas in 18%, and tendon xanthomas in 13%. Coronary artery disease was found in 47% of patients and peripheral vascular disease in 20%. Fibrates were the most commonly used hypolipidaemic agents (48%), while 31% of patients received combination therapy with a fibrate and statin. Statin monotherapy was used in 11% of patients and a few patients were treated with niacin or required no drug therapy. The treated cholesterol was 5.7 +/- 2.4 mmol/l, with plasma triglycerides of 2.7 +/- 1.9 mmol/l.

Dysbetalipoproteinaemia is a highly atherogenic disorder and is extremely responsive to therapy. A significant proportion of dysbetalipoproteinaemia locally is caused by the apoE2 (Arg145-->Cys) mutation and is therefore dominantly inherited. This mutation is particularly prevalent in the black community where dysbetalipoproteinaemia may be undiagnosed in many patients. Patients with severe mixed hyperlipidaemia or clinical stigmata of dyslipidaemia should be assessed at a lipid clinic for a specific diagnosis and initiation of therapy.