Comparison of clinical and molecular genetic criteria for diagnosing familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a common autosomal-dominant inherited disorder of lipid metabolism. It is caused by a mutation in the LDL-receptor gene and is characterized by hypercholesterolemia, xanthomas and premature coronary heart disease. However, efficient lipid-lowering drug therapies are available that may normalize the cholesterol levels in FH heterozygotes. FH can be diagnosed by the use of clinical diagnostic criteria or by the use of molecular genetic methods to identify a mutation in the LDL-receptor gene. In this review, we have compared the two diagnostic strategies with respect to their clinical utilities to diagnose FH heterozygotes and to promote therapeutic interventions in those being diagnosed. We conclude, that the clinical diagnostic criteria both have low sensitivity and low specificity, and should, therefore, largely be replaced by molecular genetic methods in order to obtain a specific diagnosis that may form the basis for implementing preventive measures to prevent FH heterozygotes from contracting coronary heart disease.