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Biochemistry · Steroid synthesis: lipoid congenital adrenal hyperplasia
Sample itemA phenotypically female infant (46,XY karyotype) has vomiting, hyponatraemia, hyperkalaemia and marked skin pigmentation at 2 weeks. ACTH and renin are very high, and cortisol, aldosterone, 17-hydroxyprogesterone and androgens are all undetectable. The adrenals are enlarged and lipid-laden. What is the defect?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Steroidogenic acute regulatory protein, which carries cholesterol into mitochondria
The StAR protein moves cholesterol from the outer to the inner mitochondrial membrane, where side-chain cleavage forms pregnenolone, the first step of all steroid hormones. Its loss in lipoid CAH leaves every adrenal and gonadal steroid deficient, so XY infants are undervirilised, with salt wasting, and cholesterol esters pile up in the adrenals. The other enzymes block downstream steps so that some steroids persist.
Option by option
A. 17-alpha-hydroxylase
17-alpha-hydroxylase deficiency causes hypertension and hypokalaemia from excess mineralocorticoid, and cortisol deficiency without salt wasting.
B. 21-hydroxylase
21-hydroxylase deficiency gives high 17-hydroxyprogesterone and virilisation of females.
C. Steroidogenic acute regulatory protein, which carries cholesterol into mitochondria (correct)
Absent StAR blocks all steroidogenesis, explaining undetectable 17-hydroxyprogesterone and female genitalia in a 46,XY infant.
D. 11-beta-hydroxylase
11-beta-hydroxylase deficiency gives raised 11-deoxycorticosterone and hypertension with virilisation.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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