Neonatal screening for congenital adrenal hyperplasia.
Congenital adrenal hyperplasia (CAH) caused by steroid 21-hydroxylase deficiency occurs in 1:16,000-1:20,000 births. If not promptly diagnosed and treated, CAH can cause death in early infancy from shock, hyponatremia and hyperkalemia. Affected girls usually have ambiguous genitalia but boys appear normal; therefore, newborn babies are commonly screened for CAH in the US and many other countries. By identifying babies with severe, salt-wasting CAH before they develop adrenal crises, screening reduces morbidity and mortality, particularly among affected boys. Diagnosis is based on elevated levels of 17-hydroxyprogesterone, the preferred substrate for steroid 21-hydroxylase. Initial testing usually involves dissociation-enhanced lanthanide fluorescence immunoassay that has a low positive predictive value (about 1%), which leads to many follow-up evaluations that have negative results. The positive predictive value might be improved by second-tier screening using DNA-based methods or liquid chromatography followed by tandem mass spectrometry, but these methods are not widely adopted. Cost estimates for such screening range from US$20,000 to $300,000 per life-year saved. In babies with markedly abnormal screen results, levels of serum electrolytes and 17-hydroxyprogesterone should be immediately determined, but the most reliable way to diagnose CAH is measurement of levels of steroid precursors after stimulation with cosyntropin.
White
Perrin C
PC
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA. perrin.white@utsouthwestern.edu
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000175:diagnosis*; D004573:Electrolytes / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000191:economics
D004573:Electrolytes; D019326:17-alpha-Hydroxyprogesterone
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