Rare diseases
The prevalence of congenital adrenal hyperplasia is estimated between 1/10,000 and 1/15,000 births. The disease is less common in Japan but may be more prevalent in some more restricted ethnic groups.
Congenital adrenal hyperplasia (CAH) refers to a group of disorders resulting from defective steroidogenesis. There are several types of congenital adrenal hyperplasia described: deficiency of 21-Hydroxylase, 17-α-Hydroxylase, 3-β-Hydroxysteroid Dehydrogenase, 11-β-Hydroxylase, or Cytochrome P450 Oxidoreductase and finally congenital lipoid adrenal hyperplasia.
In more than 90-95% of cases, CAH is caused by a mutation in the CYP21A2 gene. This gene encodes an enzyme, 21-Hydroxylase, which controls the production of cortisol and aldosterone in the adrenal gland. This 21-Hydroxylase deficiency is subdivided into two subcategories:
Approximately 75% of people with classic CAH secondary to 21-Hydroxylase deficiency have hypertrophic adrenal glands producing excessive quantities of androgens, with aldosterone deficiency. The result is excessive salt loss from birth, leading to hyponatremia, dehydration, hypovolemia and hypotension, which endangers the patient’s survival. In girls, sexual ambiguity with varying degrees of virilization is usually present. The remaining 25% are the simple virilizing forms; these individuals do not have ionic disorders.
Symptoms of non-classical CAH occur later in childhood or adolescence and may include premature excess hair, acne, or menstrual irregularities. This less severe form rarely requires early treatment.
In infants, the determination of 17-hydroxyprogesterone (17-OHP) levels can identify classic forms of 21-Hydroxylase deficiency. Because premature babies typically have higher 17-OHP concentrations, the cutoff (decision threshold) is often weighted by gestational age at birth and/or infant weight.
A comprehensive steroid panel, ionogram, and molecular analysis of the CYP21A2 gene then confirm the diagnosis.
Lifelong hormone replacement therapy is necessary to treat adrenal insufficiency and reduce high levels of androgens. This treatment includes hydrocortisone (or any other equivalent glucocorticoid), and 9-α-Fludrocortisone acetate (a mineralocorticoid substitute). Regular monitoring is essential to control the dosage.
Surgery may be done to correct sexual ambiguity in young girls. Hirsutism can be treated by hair removal and menstrual cycles regulated using oral contraceptives.
Usually, all forms of CAH transmission are autosomal recessive. The probability of recurrence in a subsequent pregnancy is 25%.
The ELIZEN Neonatal 17-OHP Screening test is an ELISA-type quantitative test for newborn screening for congenital adrenal hyperplasia. It allows for the determination of the concentration of 17-hydroxyprogesterone (17-OHP) present in a sample of blood dried on 903® or 226 blotted type paper.