Patrick RIZZUTO, Mariam GANGAT, Ahmed KHATTAB, Ian MARSHALL
Journal of Clinical Research in Pediatric Endocrinology - 2026;18(Suppl 1):92-96
21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (CAH). Salt-wasting CAH can present with life-threatening salt-wasting crises, underscoring the importance of universal newborn screening. We present a patient diagnosed with classical CAH despite four negative newborn screening (NBS). A male infant was born at 35 weeks gestation with birthweight 1470 grams following signs of placental insufficiency. While hospitalized in the neonatal intensive care unit (NICU), four NBS samples from days of life 2 to 38 were all within normal range, including on repeat analysis using fully integrated fluoroimmunoassay. After initially normal biochemical testing, hyponatremia and hyperkalemia developed by day of life (DOL) 26, responsive to sodium chloride supplementation. Following recurrent hyponatremia after a trial off supplementation after DOL 50, 17-hydroxyprogesterone measured by liquid chromatography-tandem mass spectrometry were reported by two different labs as 10,900 ng/dL and 11,200 ng/dL (normal range at DOL 50<2 ng/dL). Subsequent testing identified deletion of one CYP21A2 allele and a mutation, I172N, in the second. This report illustrates the importance of maintaining a high index of suspicion for classical forms of CAH in infants with persistent electrolyte disturbances despite negative NBS results.
