A 2-year-old girl is brought to the clinic by her mother for evaluation of ambiguous genitalia. She was born with clitoral enlargement and partial fusion of the labioscrotal folds. The patient has also had high blood pressure recorded on 3 consecutive office visits. She has been tracking at the 50th percentile for height and weight, and has not had any other medical problems. Family history is noncontributory. Laboratory studies are significant for moderate hypokalemia. Cytogenetic studies show a 46,XX karyotype. Which of the following enzymes is most likely deficient in this patient?

Question

A 2-year-old girl is brought to the clinic by her mother for evaluation of ambiguous genitalia.  She was born with clitoral enlargement and partial fusion of the labioscrotal folds.  The patient has also had high blood pressure recorded on 3 consecutive office visits.  She has been tracking at the 50th percentile for height and weight, and has not had any other medical problems.  Family history is noncontributory.  Laboratory studies are significant for moderate hypokalemia.  Cytogenetic studies show a 46,XX karyotype.  Which of the following enzymes is most likely deficient in this patient?

Quizplus · Accepted Answer

11ec160b_3ab0_d019_9249_59296ab16077_MD0001_00 This girl with ambiguous genitalia, hypertension, and hypokalemia most likely has 11β-hydroxylase deficiency, the second-most common cause of congenital adrenal hyperplasia after 21-hydroxylase deficiency. 11β-hydroxylase is responsible for converting 11-deoxycorticosterone to corticosterone and 11-deoxycortisol to cortisol. Enzyme deficiency results in the buildup of aldosterone and cortisol precursors, which are then shunted toward adrenal androgen synthesis. In genetically female infants, androgen excess leads to ambiguous genitalia (virilization). Although 11β-hydroxylase deficiency inhibits aldosterone synthesis, 11-deoxycorticosterone accumulates and acts as a weak mineralocorticoid, causing affected individuals to have hypertension and hypokalemia. (Choice A) 5α-reductase deficiency causes ambiguous genitalia in boys due to the defective conversion of testosterone to dihydrotestosterone. Girls have normal genitalia, and blood pressure and electrolytes are unaffected. (Choice C) 17α-hydroxylase deficiency results in impaired sex steroid and cortisol synthesis, and increased production of mineralocorticoids. Girls are born with normal genitalia, but boys are born undervirilized (ambiguous genitalia). Affected individuals develop hypertension and hypokalemia (mineralocorticoid excess) and do not undergo puberty (no sex steroids). (Choice D) 21-hydroxylase deficiency decreases glucocorticoid and mineralocorticoid synthesis and increases adrenal androgen production. Girls are born with ambiguous genitalia (androgen excess) and frequently develop hypotension and hyperkalemia (mineralocorticoid deficiency). (Choice E) Side-chain cleavage enzyme converts cholesterol to pregnenolone. Because this is the first enzyme in the steroidogenic pathway, deficiency impairs synthesis of all steroid hormones. Complete deficiency is lethal due to absent placental progesterone synthesis. Educational objective: 11β-hydroxylase deficiency typically results in excessive adrenal androgen and mineralocorticoid (11-deoxycorticosterone) production. Genetically female infants are born with ambiguous genitalia, and affected individuals develop hypertension and hypokalemia early in life. __________ References: Clinical perspectives in congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/27928728)

A 2-Year-Old Girl Is Brought to the Clinic by Her