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Congenital adrenal hyperplasia - CYP21A2

Clinical Features

Congenital adrenal hyperplasia comprises a family of autosomal recessive disorders with impaired cortisol synthesis. Different forms can be distinguished:

• classic form           
  • with virilization and salt wasting           
  • simple virilization without salt wasting
• mild / late-onset / non classic form

Loss of enzyme activity causes the classic form with salt wasting and virilization (prenatal onset). Newborns with the salt wasting form are at risk for life-threatening salt wasting crises. In case of residual enzyme activity the simple virilizing form without salt-wasting is observed.

Patients with the mild form present with postnatal signs of hyperandrogenism as hirsutism, rapid growth, menstrual abnormalities, reduced fertility or metabolic syndrome/PCO. In females with reduced fertility and conspicuous ACTH-testing CAH-screening should be performed, to identify patients with a mild form of CAH. In case of CYP21A2-mutations a therapy can be offered and risk for future children can be elucidated early. Due to high heterozygote frequency screening of the partners for CYP21A2-mutations is recommended in these cases.

Patients with CAH get a lifetime therapy. Children with classic salt wasting form get a mineralcorticoid replacement therapy and sodium chloride. In case of the classic form without salt wasting or the mild form glucocorticoids are substituted. After completion of growth prednisone or dexamethasone can be used.

Families at risk for a child with classic form of CAH should be informed on possibilities of a prenatal therapy and prenatal diagnostics to avoid prenatal virilization of an affected female fetus.

Genetic Information

More than 95% the cases are caused by a defect of the 21-hydroxylase gene (CYP21A2, chromosome 6p21.3). Defects of 11ß-hydroxylase, 3ß-hydroxysteroiddehydrogenase or 17α-hydroxylase are rare.

Prevalence

In the European population:

• classic form ca. 1 : 12 000
• prevalence of carriers classic form ca. 1 : 40
• prevalence of carriers non classic form ca. 1:10 – 1:25

Diagnostic