Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (69 page)

   TC is very high (600–1,000 mg/dL) with corresponding increase in LDL.

   Neonatal diagnosis requires finding increased LDL-C in cord blood; serum TC is unreliable. Because of marked variation in serum TC levels during the 1st year of life, diagnosis should be deferred until 1 year of age. Prenatal diagnosis of homozygous fetus can be made by estimation of binding sites on fibroblasts cultured from amniotic fluids; useful when both parents are heterozygous.

   Heterozygous

   Increased serum TC (300–500 mg/dL) and LDL (two to three times normal) with similar change in a parent or first-degree relative; serum TG and VLDL are normal in 90% and slightly increased in 10% of these cases.

   Gene frequency occurs in 1 in 500 in the general population, but 5% in survivors of acute myocardial infarction (AMI) <60 years old. Plasma TG is normal in type II-A but increased in type II-B. This is not the most common cause of phenotype II-A.

   LDL receptors in fibroblasts or mononuclear blood cells are <25% in homozygous and 50% of normal levels.

POLYGENIC HYPERCHOLESTEROLEMIA (TYPE IIA)

   Definition

   Polygenic hypercholesterolemia can be diagnosed only after secondary causes of hypercholesterolemia and autosomal dominant traits have been excluded.

   Premature CAD occurs later in life than with familial combined hyperlipidemia. Xanthomas are rare.

   Laboratory Findings

   Persistent TC elevation (>240 mg/dL) and increased LDL without familial hypercholesterolemia or familial combined hypercholesterolemia.

   In type IIB disease, both LDL and VLDL are increased.

FAMILIAL COMBINED HYPERLIPIDEMIA (TYPES IB, IV, V)

   Definition