Ann Pediatr Endocrinol Metab.  2015 Mar;20(1):1-7. 10.6065/apem.2015.20.1.1.

Clinical and molecular review of atypical congenital adrenal hyperplasia

• Sahakitrungruang T

• KMID: 1789524
• DOI: http://doi.org/10.6065/apem.2015.20.1.1

Abstract

Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the mutations in the genes encoding for steroidogenic enzymes that involved cortisol synthesis. More than 90% of cases are caused by a defect in the enzyme 21-hydroxylase. Four other enzyme deficiencies (cholesterol side-chain cleavage, 17alpha-hydroxylase [P450c17], 11beta-hydroxylase [P450c11beta], 3beta-hydroxysteroid dehydrogenase) in the steroid biosynthesis pathway, along with one cholesterol transport protein defect (steroidogenic acute regulatory protein), and one electrontransfer protein (P450 oxidoreductase) account for the remaining cases. The clinical symptoms of the different forms of CAH result from the particular hormones that are deficient and those that are produced in excess. A characteristic feature of CAH is genital ambiguity or disordered sex development, and most variants are associated with glucocorticoid deficiency. However, in the rare forms of CAH other than 21-hydroxylase deficiency so-called "atypical CAH", the clinical and hormonal phenotypes can be more complicated, and are not well recognized. This review will focus on the atypical forms of CAH, including the genetic analyses, and phenotypic correlates.

Keyword

Congenital adrenal hyperplasia; Rare disease; Genotypes; Phenotypes

MeSH Terms

Adrenal Hyperplasia, Congenital*
Cholesterol
Disorders of Sex Development
Genotype
Hydrocortisone
Phenotype
Rare Diseases
Sexual Development
Steroid 21-Hydroxylase
Cholesterol
Hydrocortisone
Steroid 21-Hydroxylase

Figure

• 

  Fig. 1 Simplified scheme of adrenal steroidogenesis. AKR, aldo-keto reductase; Cyt.b5, cytochrome b5; P450scc, cholesterol side-chain cleavage enzyme; P450c17, 17α-hydroxylase/17,20-lyase; 3βHSD2, 3β-hydroxysteroid dehydrogenase type 2; P450c21, 21-hydroxylase; P450c11AS, aldosterone synthase; P450c11β, 11β-hydroxylase; POR, P450 oxidoreductase; StAR, steroidogenic acute regulatory protein; SULT2A1, sulfotransferase; 18OHCort, 18-hydroxycorticosterone.

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