Type IV hyperlipoproteinaemia

Endogenous hyperglyceridaemia, or type IV hyperlipoproteinaemia is the most common variety of triglyceride elevation. The minimal requirements to make the chemical diagnosis of type IV H.L.P. include sampling blood under standardised conditions, observation of standing plasma, and measurement of plasma cholesterol and triglycerides. Elimination of the many phenocopies of type IV H.L.P. is necessary before a diagnosis of primary type IV H.L.P. can be made. Family screening is currently required to document the familial nature of this disorder, because no qualitative markers of the type IV H.L.P. are presently available. Although familial type IV H.L.P. is undoubtedly heterogeneous, it behaves in some families as a Mendelian dominant trait with delayed penetrance. The clinical manifestations of type IV H.L.P. vary in different patients but include premature vascular disease of the coronary and peripheral vessels, xanthomas, and acute pancreatitis. Glucose intolerance, diabetes and hyperuricaemia are other common findings in these patients. The metabolism of VLDL is complex and involves the interrelationships of lipid, carbohydrate and lipoprotein metabolism. Possible biochemical defects in type IV H.L.P. may involve the synthesis, secretion or catabolism of VLDL. The presence of carbohydrate intolerance may be a clue to the defects in type IV H.L.P. The possible role of insulin in the pathogenesis of the disorder(s) is unsettled; peripheral resistance to insulin, insulin deficiency and hyperinsulinism have all been implicated in type IV H.L.P. Treatment of the hyperglyceridaemia in the patient with type IV H.L.P. is indicated for two reasons: first, to relieve or avoid the complications of severe hyperglyceridaemia, e.g. eruptive xanthomas or pancreatitis; and, secondly, hopefully to prevent or regress premature coronary and peripheral vascular disease. Epidemiological and family studies have demonstrated a relationship between elevated plasma triglyceride levels and the risk of coronary heart disease. Although it has not been proven that lowering cholesterol or triglyceride levels will alter the atherosclerotic process, treatment appears judicious at this point. The cornerstone of therapy for type IV H.L.P. is diet. Drug therapy is indicated in some patients and either clofibrate (Atromid-S) or nicotinic acid has been used with some success.