Hyperlipoproteinemia

About one in five persons with elevated plasma lipid and lipoprotein levels has hyperlipoproteinemia, an inherited disorder marked by increased plasma concentrations of one or more lipoproteins. Hyperlipoproteinemia may also occur secondary to other conditions, such as diabetes, pancreatitis, hypothyroidism, and renal disease.

This disorder affects lipid transport in serum and produces varied clinical changes, from relatively mild symptoms that can be corrected by dietary management to potentially fatal pancreatitis.

Hyperlipoproteinemia occurs as five distinct metabolic disorders. Types I and III are transmitted as autosomal recessive traits; types II, IV, and V are transmitted as autosomal dominant traits.

Causes

Each type of hyper lip oproteinemi a has distinct causes and incidence.

Signs and symptoms

Clinical features of hyperlipoproteinemia vary according to the type of disorder:

• Type I: recurrent attacks of severe abdominal pain similar to pancreatitis, usually preceded by fat intake; abdominal spasm, rigidity, or rebound tenderness; hepatosplenomegaly with liver or spleen tenderness; papular or eruptive xanthomas (pinkish yellow cutaneous deposits offat) over pressure points and extensor surfaces; lipemia retinalis (reddish white retinal vessels); malaise; anorexia; and fever
• Type II: tendinous xanthomas (firm masses) on the Achilles tendons and tendons of the hands and feet, tuberous xanthomas, xanthelasma, juvenile corneal arcus (opaque ring surrounding the corneal periphery), accelerated atherosclerosis and premature coronary artery disease (CAD), and recurrent polyarthritis and tenosynovitis.
• Type III: peripheral vascular disease manifested by claudication or tuboeruptive xanthomas (soft, inflamed, pedunculated lesions) over the elbows and knees; palmar xanthomas on the hands, particularly fingertips; premature atherosclerosis
• Type IV: predisposition to atherosclerosis and early CAD, exacerbated by excessive calorie intake, obesity, diabetes, and hypertension
  
• Type v: abdominal pain (most common), pancreatitis, peripheral neuropathy, eruptive xanthomas on extensor surfaces of the arms and legs, lipemia retinalis, and hepatosplenomegaly.

Diagnosis

Diagnostic findings vary among the five types of hyperlipoproteinemia.

Treatment

The first goal is to identifY and treat any underlying problem such as diabetes. If no underlying problem exists, the primary treatment for types II, III, and IV is dietary management, especially restriction of cholesterol intake. Drug therapy (cholestyramine, clofibrate, or niacin) may also be used to lower the plasma triglyceride or cholesterol level when diet alone is ineffective.

Type I

In type I hyperlipoproteinemia, treatment requires long term weight reduction, with fat intake restricted to less than 20 g/day. A 20- to 40-g/day medium-chain triglyceride diet may be ordered to supplement caloric intake. The patient should also avoid alcoholic beverages to decrease plasma triglycerides. The prognosis is good with treatment; without treatment, death can result from pancreatitis.

Type II

For type II, dietary management to restore normal lipid levels and decrease the risk of atherosclerosis includes restriction of cholesterol intake to less than 300 mg/day for adults and less than I50 mg/day for children; triglyceride levels must be restricted to less than 100 mg/day for children and adults. The diet should also be high in polyunsaturated fats.

In familial hypercholesterolemia, nicotinic acid with a bile acid usually normalizes low-density lipoprotein levels. For severely affected children, portacaval shunt is a last resort to reduce plasma cholesterol levels.

The prognosis remains poor regardless of treatment; in homozygotes, myocardial infarction usually causes death before age 30.

Type III

For type III, dietary management includes restriction of cholesterol intake to less than 300 mg/day; carbohydrates must also be restricted, and polyunsaturated fats are increased. Clofibrate and niacin help lower blood lipid levels. Weight reduction is helpful. With strict adherence to the prescribed diet, the prognosis is good.

Type IV

For type IV, weight reduction may normalize blood lipid levels without additional treatment. Long-term dietary management includes restricted cholesterol intake, increased polyunsaturated fats, and avoidance of alcoholic beverages. Clofibrate and niacin may lower plasma lipid levels.

The prognosis remains uncertain because of predisposition to premature CAD.

Type V

The most effective treatment for type V is weight reduction and long-term maintenance of a low-fat diet. Alcoholic beverages must be avoided. Niacin, clofibrate, gemfibrozil, and a 20- to 40-g/day medium-chain triglyceride diet may prove helpful.

The prognosis is uncertain because of the risk of pancreatitis. Increased fat intake may cause recurrent bouts of illness, possibly leading to pseudocyst formation, hemorrhage, and death.

Prevention

Genetic inheritance cannot be changed, but its effects may be modified with proper treatment. Family members of an individual with hyperlipoproteinemia should consider having their blood lipids assessed. The sooner any problems are identified, the better the chances of limiting or preventing the associated health risks. Anyone with a family history of disorders leading to hyperlipoproteinemia also may benefit from genetic testing and counseling to assist them in making reproductive decisions.