Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency*

Abstract

More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21-hydroxylase deficiency. Females with severe, classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilized external genitalia. Most patients cannot synthesize sufficient aldosterone to maintain sodium balance and may develop potentially fatal "salt wasting" crises if not treated. The disease is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombinations between CYP21 and the closely linked CYP21P pseudogene. Approximately 20% are gene deletions due to unequal crossing over during meiosis, whereas the remainder are gene conversions--transfers to CYP21 of deleterious mutations normally present in CYP21P. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disease in patients carrying it. Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition. Glucocorticoid and mineralocorticoid replacement are the mainstays of treatment, but more rational dosing and additional therapies are being developed.

Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

“…Adrenal crises may present with weakness, vomiting, abdominal pain or confusion, and may cause shock, coma, and death, if untreated (5). For the prevention of adrenal crises in all conditions of major physical stress, such as trauma, infection, fever, or surgery, glucocorticoid doses must be augmented, and parenteral administration of glucocorticoids may be necessary (1). Medical identification should always be carried by the patient (6,7,8).…”

Determining clinical and biological indicators for health outcomes in adult patients with childhood onset of congenital adrenal hyperplasia

“…Twenty-one-hydroxylase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia (CAH) (1,2). CAH is classified according to symptoms, age of presentation, and genetics, and it is usually divided into two forms: classic, or severe, form (CF) and non-classic form (NCF).…”

Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening

“…Concluindo, a criança é apenas heterozigota da mutação p.V281L sem necessidade de tratamento. S teroid 21-hydroxylase defi ciency (21-OHD; OMIM +201910) is an autossomal disorder that accounts for more than 90% of congenital adrenal hyperplasia (CAH) (1,2). Impaired 21-hydroxylase activity results in decreased cortisol and aldosterone levels.…”

“…Impaired 21-hydroxylase activity results in decreased cortisol and aldosterone levels. Frequently, the classical 21-OHD causes ambiguous external genitalia at birth in females, precocious puberty in males, and acceleration of somatic growth in both sexes (1,2). If the level of the enzyme impairment is higher than 99%, mineralocorticoid synthesis is severely affected leading to salt-wasting crisis.…”