Congenital adrenal hyperplasia- an example of gene error in enzyme expression: the defect in one enzyme, ‘backlashes’ in the other.

 The human body is like a test tube. Thousands of reactions, catalysed by enzymes go on simultaneously. The system of reactions are intricately interconnected, in as much, that the slowing or absence of enzyme activity in one pathway leads to a compensatory increase in the interconnected pathways. The system is analogous to a traffic blockade in a thoroughfare, that leads to spontaneous diversion of the traffic to the adjacent interconnected roads. The biochemical ‘conglomerate’ runs mechanisms that propels the human body to struggle and survive. Stressors are plenty and the body responds adequately and timely. The adrenal gland is the seat of the response to stress. Adrenaline from adrenal medulla fills the body with energy and ‘strength’ in the hour of acute stress. Simultaneously, at all times, be it the ‘acute stress’ or otherwise, the adrenal cortex continuously ‘infuses’ the  corticosteroids into the circulation to maintain the state of ‘vigil’ required for ‘existence’. The adrenal cortex synthesises three important hormones- the Glucocorticoids, mineralocorticoids and androgens. The parent ‘raw material’ of the three hormones is same, and is nothing but cholesterol. In Congenital Adrenal Hyperplasia (CAH), the enzymes synthesising aldosterone and cortisol are partially or completely repressed. Low serum cortisol exerts a feedback stimulation on the pituitary to produce large quantities of ACTH. The result of ACTH action on adrenal cortex is adrenal hyperplasia. However, the adrenal overgrowth is not able to produce aldosterone or cortisol. Instead, the enzymatic machinery is diverted towards production of large amounts of androgens. Depending upon the degree of enzyme repression, a female child may present with ambiguous genitalia at birth or virilization features with growth; a male child may develop precocious puberty; and both male and female child may present at birth with extreme salt wasting, vomiting, dehydration, hyponatremia and failure to thrive. While extreme salt wasting and dehydration is an emergency, necessitating fluid and electrolyte replacement, long term management of the condition involves replacements ment of  cortisol or aldosterone or both depending upon the deficiencies. Surgical management of ambiguous genitalia is not a life saving measure but options for corrective surgical procedures should be kept open for the proper psychological and social rehabilitation of the patient.