Assessing the risk of having a child with classic 21-hydroxylase deficiency: a new paradigm.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a complicated condition genetically, clinically, and treatment wise. Genetically, there are numerus mutations with different effect on enzyme activity that make genetic diagnosis a challenge. Clinically, there are a wide range of presentations from asymptomatic patients to the severe life-threatening classic CAH. Both an asymptomatic heterozygote and a mildly affected non-classical patient can carry a 'severe' mutation and endow it to their offspring. We present a case of non-classic CAH and discuss the problematic relations between biochemical and genetic diagnosis. By integrating the seemingly contradicting literature, we provide a new simple tool to assess the risk of such patients to give birth to a child with classic CAH. Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency varies clinically from asymptomatic or mild disease (non-classic), through 'simple virilizing' type, to a severe life-threatening condition (classic) due to adrenal insufficiency. 'Classic' CAH patient must harbor two 'severe' mutations, one on each of the alleles of the 21OH gene. Prevention of the birth of a child with classic disease is a challenge as the heterozygote carrier of 'severe' mutation is usually asymptomatic with normal biochemical tests, and a 'non-classic' patient can still carry a 'severe' mutation. Genetic diagnosis is a challenge, as there are numerus mutations including deletions, intronic mutations, double and triple mutations, and pseudogenes. In this article, we provide a new simple tool to assess the risk of a couple to give birth to a child with 'classic' disease. [ABSTRACT FROM AUTHOR]