Neonatal mass screening for 21-hydroxylase deficiency

Abstract. Congenital adrenal hyperplasia(CAH)due to 21-hydroxylase deficiency (21-OHD) is an inherited autosomal recessive disorder. Its incidence is 1 in 10,000 to 20,000 worldwide. This disease shows phenotypic differences, and it is divided into three forms i.e., the salt wasting (SW), simple virilizing (SV), and nonclassic (NC) forms. The most severe form of SW manifests in the first months of life with life-threatening adrenal insufficiency, leading to death. To prevent death by adrenal insufficiency in neonates with the SW form and wrong gender assignment of 46,XX female patients with SW and SV, neonatal mass screening of 21-OHD is performed in several countries including Japan. However, the positive predictive value (PPV) remains low, especially in preterm infants. To reduce the false positive rate and increase the PPV, liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) as a second-tier test may be useful. In this review, the current knowledge on neonatal mass screening of 21-OHD is summarized.