Madurai, India.

Introduction

Congenital adrenal hyperplasia is most commonly caused by 21-hydroxylase deficiency which results in impaired cortisol production from cholesterol and increased production of androgens. It is a most common cause of the ambiguous genitalia. This condition causes virilization of the external genitalia of genetic females. Such affected neonates have ambiguous genitalia at birth. This can be diagnosed during the prenatal ultrasound examination as well.

It can be a life-threatening condition due to decreased corticosteroid (aldosterone) production resulting in salt wasting. The affected neonates have markedly increased level of 17- hydroxyprogesterone. The classic form of this condition has a prenatal onset. Non-classic form has usually mild enzyme deficiency and postnatal onset.

In case of prenatal diagnosis of this condition, prenatal treatment with dexamethasone reduces virilization of the affected females. This prevents them from a postnatal surgery.

Inheritance: autosomal recessive disorder.

Genetic testing

The only known gene associated with 21-hydroxylase deficiency is CYP21A2. Most parents of affected children are heterozygous with one normal and one mutated allele. 1% of mutations occur de novo.There are 9 common mutations of the CYPD1A2 gene which can be detected by molecular genetic testing. Entire gene sequencing is required in order to discover rarer mutations.

Images 1,2: Sagittal view of the abdomen showing kidney (red) and enlarged adrenal gland (pink).