Clinical Spectrum Genetic Characterization and Effect of Glucocorticoids on Bone Mineral Density in Children with Congenital Adrenal Hyperplasia

Abstract

Congenital Adrenal Hyperplasia [CAH] is an autosomal recessive disorder of cortisol biosynthesis that occurs due to defect in one of the five enzymatic steps which are required for the synthesis of cortisol from cholesterol. The term CAH is used because the adrenal glands are hyperplastic at birth due to unrestrained adreno corticotrophic hormone [ACTH] stimulation in fetal life.1 The most common form of CAH is due to 21 hydroxylase enzyme deficiency (21OHD) which accounts for more than 90% of the cases.2 The other enzymatic causes include 11 and#946; hydroxylase deficiency, 3and#946; hydroxysteroid deficiency, 17 and#945; hydroxylase deficiency, Steroidogenic acute regulatory protein (StAR) congenital lipoid adrenal hyperplasia and P 450 oxidoreductase deficiency. The present study focuses on congenital adrenal hyperplasia due to 21 hydroxylase deficiency. newlineIn this series of children with classical salt wasting congenital adrenal hyperplasia, the mean age at diagnosis was 22 days and the majority were born to parents of consanguineous marriage. newlineMolecular genetic testing in CAH is definitely beneficial when the clinical features are atypical and there is a dilemma in diagnosis. In this small group of children with classical salt wasting CAH due to 21 hydroxylase deficiency, 8 bp deletion in exon 3 was the commonest mutation. This observation of a particular type of mutation documented in children with CAH will help to make a reliable prenatal diagnosis and also offer genetic counseling to the affected families. newlineLumbar spine and TBLH BMD values in children with CAH were similar to that of controls in the present study. However lumbar spine and TBLH BMC is reduced in children with congenital adrenal hyperplasia when compared with controls though the difference was not statistically significant. Hence children with CAH should be treated with appropriate dosage of glucocorticoids with periodic monitoring of bone mineral parameters. newline newline