LBODP087 Unusual Presentation Of Salt-wasting 3-beta-hydroxysteroid Dehydrogenase-2 Deficiency

Abstract

Abstract Background Biallelic pathogenic variants of HSD3B2 cause 3-beta-hydroxysteroid dehydrogenase-2 (3BHSD2) deficiency. 3BHSD2 is a rare cause of congenital adrenal hyperplasia (CAH) with two presentations in infancy including salt-wasting and a non-salt wasting with variable virilization of females and undervirilization of males (1). The salt-wasting form is usually not detected on newborn screen (NBS) and often presents with a potentially fatal adrenal crisis. We report a case of salt-wasting 3BHSD2, initially diagnosed as salt-wasting 21-hydroxylase deficiency following an abnormal newborn screen. Clinical case: A now 5.3 year old female was born at term, birthweight 3.44 kg, with no known pregnancy or neonatal problems. The first NBS at two days old was normal. The second NBS at 16 days old showed very high 17-hydroxyprogesterone (17OHP). She was clinically healthy with mild labial hyperpigmentation and rugation, and her clitoris was 1 cm in length. However, she had low sodium, elevated potassium, and elevated 17OHP with Na 127 mmol/L (RR 134-144), K 9.1 mmol/L (RR 3.5-5.2), and 17-OHP 5440 ng/dL (HPLC-MS/MS; RR 7-106). Glucocorticoid and mineralocorticoid replacement was initiated. She remained healthy with suppressed 17OHP and renin and full regression of virilization led to suspicion of the presumptive diagnosis of 21-hydroxylase deficiency. At 3 to 4 years old, CYP21A2 and CYP11B1 analyses were both resulted normal. At 4.5 years old following a two day therapeutic withdrawal test, her labs were as follows: ACTH 1940 pg/mL (RR 7-63), 17OHP 147 ng/dL (RR <299), DHEA 7240 ng/mL (RR 50-995), 17-hydroxypregnenolone 10405 ng/dL (RR ≤280) and pregnenolone 1352 ng/dL (RR 15-125). Her electrolytes were normal and all other adrenal precursors were within the normal reference range. Her diagnosis has since been revised to 3BHSD2 deficiency. At the time of submission, genetic confirmation is pending. Conclusion This case illustrates the variable presentation of this rare condition, and the value of genetic testing in CAH. The cause of the transient 17OHP elevation and mild virilization is uncertain; however, a possible relationship to persistent fetal adrenal is postulated.