21-Hydroxylase Deficiency screening

Template:21-Hydroxylase Deficiency Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Newborn screening

Conditions justifying newborn screening for any disorder include (1) a simple test with an acceptable sensitivity and specificity, (2) a dire consequence if not diagnosed early, (3) an effective treatment if diagnosed, and (4) a frequency in the population high enough to justify the expense. In the last decade more states and countries are adopting newborn screening for salt-wasting CAH due to 21-hydroxylase deficiency, which leads to death in the first month of life if not recognized.

The salt-wasting form of CAH has an incidence of 1 in 15,000 births, is potentially fatal within a month if untreated, and steroid replacement is a simple, effective treatment. However, the screening test itself is less than perfect. While the 17OHP level is easy to measure and sensitive (rarely missing real cases), the test has a poorer specificity. Screening programs in the United States have reported that 99% of positive screens turn out to be false positives upon investigation of the infant. This is a higher rate of false positives than the screening tests for many other congenital metabolic diseases. While each screen costs less than US$2, the program costs well over US$100,000 for each case detected.

When a positive result is detected, the infant's family and doctor must be notified, and the infant must be referred to a pediatric endocrinologist to confirm or disprove the diagnosis. Since most infants with salt-wasting CAH become critically ill by 2 weeks of age, the evaluation must be done rapidly despite the high false positive rate.