Heterozygote tests and genetic counseling in maple syrup urine disease: an application of Baye's theorem.

The discriminatory power of a quantitative heterozygote test for Maple Syrup Urine Disease (MSUD) which we have been using is analyzed on the presumption that a single rare mutant allele is involved in MSUD. Bayes theorem then predicts that only a small portion of persons from the general population with activities in the heterozygous range really are heterozygotes. In addition, overlap of heterozygous and normal homozygous activity distributions requires rather high activities in first-cousin matings of a patient's sib in order to obviate the necessity for prenatal diagnosis. Thus, the principle emerges that quantitative heterozygote tests for rare autosomal recessive diseases cannot fulfill the task they were designed for.