It is a familial disorder of adrenal steroid biosynthesis with autosomal recessive mode of inheritance.
The defect is expressed as adrenal enzyme deficiency.
5 major Enzymes deficiency are clinically important
20,22 Desmolase deficiency
The enzyme deficiency causes reduction in end-products, accumulation of hormone precursors & increased ACTH production.
The clinical picture reflects the effects of inadequate production of cortisol and aldosterone and the increased production of androgens and steroid metabolites.
Most common type, accounts for >80% of cases.
Incidence is 1:5000 to 1:15000 live birth.
Gene is located on the short arm of chromosome 6 near the C4 locus in close association with HLA genes.
Heterozygous carriers can be detected by ACTH stimulation test.
It is characterized by reduced production of cortisol and aldosterone and increased production of progesterone;17-OH-progesterone, and sex steroids.
The urinary steroid metabolites (17-ketosteroids and pregnanetriol) are elevated above normal levels.
Decreased secretion of aldosterone results in salt loss with hyponatremia and hyperkalemia; plasma renin activity is therefore elevated.
In partial enzyme deficiencies, the aldosterone deficiency is not expressed, and patients remain normonatremic and normokalemic.
The excess androgens causes virilization of girls & ambiguous genitalia & dark scrotum in boys.
2 forms, classic early virilization type with or without salt-losing crisis and non-classic type with late-onset virilization.
Male babies with non salt-losing non-classic type remains asymptomatic till late childhood when they may show signs of sexual precocity.
Because members of the same family may have classic, non-classic & asymptomatic forms, the disorder may be due to allelic variations of the same enzyme.
Mass neonatal screening using filter paper blood sample for 17-OH-Progesterone is used in the USA.