CAH - The n ew england journal of m edicine r eview article...

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review article The new england journal of medicine n engl j med 349;8 august 21, 2003 776 medical progress Congenital Adrenal Hyperplasia Phyllis W. Speiser, M.D., and Perrin C. White, M.D. From the Department of Pediatrics, Schneider Children’s Hospital–North Shore–Long Island Jewish Health System, New Hyde Park, N.Y. (P.W.S.); New York University Medical Center, New York (P.W.S.); and the Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas (P.C.W.). Address reprint requests to Dr. Speiser at Schneider Children’s Hospital, 269-01 76th Ave., New Hyde Park, NY 11042, or at pspeiser@ N Engl J Med 2003;349:776-88. Copyright © 2003 Massachusetts Medical Society. ongenital adrenal hyperplasia is a group of autosomal re- cessive disorders resulting from the deficiency of one of the five enzymes re- quired for the synthesis of cortisol in the adrenal cortex. The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90 percent of cases. Since the last Medical Progress article on this topic was published in the Journal in 1987, 1 much has been learned about the genetics of the various clinical forms of 21-hydroxy- lase deficiency, and correlations between the genotype and the phenotype have been ex- tensively studied. Gene-specific prenatal diagnosis is now feasible, and prenatal treat- ment has been more widely implemented. This discussion will be limited to the most common form of congenital adrenal hyperplasia. Steroid 21-hydroxylase (CYP21, also termed CYP21A2 and P450c21) is a cytochrome P-450 enzyme located in the endoplasmic reticulum. It catalyzes the conversion of 17-hydroxyprogesterone to 11-deoxycortisol, a precursor of cortisol, and the conver- sion of progesterone to deoxycorticosterone, a precursor of aldosterone (Fig. 1). Owing to this loss of enzyme function, patients with 21-hydroxylase deficiency can- not synthesize cortisol efficiently, and as a result, the adrenal cortex is stimulated by cor- ticotropin and overproduces cortisol precursors. Some of these precursors are diverted to the biosynthesis of sex hormones, which may cause signs of androgen excess, includ- ing ambiguous genitalia in newborn girls and rapid postnatal growth in both sexes. Con- comitant aldosterone deficiency may lead to salt wasting with consequent failure to thrive, hypovolemia, and shock. A spectrum of phenotypes is observed. A severe form with a concurrent defect in aldos- terone biosynthesis (salt-wasting type) and a form with apparently normal aldosterone biosynthesis (simple virilizing type) are together termed classic 21-hydroxylase defi- ciency. There is also a mild, nonclassic form that may be asymptomatic or associated with signs of postnatal androgen excess. 2 Classic 21-hydroxylase deficiency is detected in approximately 1 in 16,000 births in most populations. 3 The nonclassic form occurs in approximately 0.2 percent of the gen- eral white population but is more frequent (1 to 2 percent) in certain populations, such as Jews of Eastern European origin.
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This note was uploaded on 10/14/2010 for the course ZOO 4125 taught by Professor Flanigan during the Fall '10 term at Univeristy of Wyoming- Laramie.

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CAH - The n ew england journal of m edicine r eview article...

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