SUN-402 Aldosterone Synthase Deficiency Caused by Two Novel Variants in a Hispanic Newborn

Abstract Disclosure: N. Jain: None. M. Jacob: None. BACKGROUND: Aldosterone synthase deficiency (ASD) can present as salt-wasting crisis and failure to thrive after the first week of life. Previous diagnoses of ASD have been found in individuals of non-Hispanic origin. CLINICAL CASE: A 9-day-old ex-35 week gestation Hispanic female (Ecuadorian origin) was transferred to the neonatal intensive care unit for failure to thrive, losing over 20% of birth weight. The neonatal course was notable for intermittent episodes of hypoglycemia requiring intravenous dextrose-containing fluids. Laboratory evaluation was remarkable for K+ > 10.0 mmol/L (3.5-5.1 mmol/L), Na 121 mmol/L (136-145 mmol/L), BUN 38 mg/dL (7-18 mg/dL), Cr 0.39 mg/dL (0.55-1.20 mg/dL), and bicarbonate 16 mEq/L (21-32 mE/L). Renal ultrasound showed trace fullness of the pelvis and renal calyces. Physical examination was notable for signs of dehydration and no evidence of atypical genitalia. Further evaluation ruled out salt-wasting congenital adrenal hyperplasia with a normal cortisol of 36.5 ug/dL (4.3-22.4 ug/dL) and state newborn screen. Additional evaluation showed normal plasma renin activity 17.91 ng/mL/hr (2.00-37.99 ng/mL/hr) but an undetectable aldosterone level < 1 ng/dL, thereby suggesting primary hypoaldosteronism. Duo rapid whole genome sequencing (rWGS) identified two novel likely pathogenic variants found in trans and consistent with CYP11B2 gene-related disease, ASD: c.1201-2A>C affecting intron 8 of CYPB11B2 and a 39-KB deletion at 8q24.3 affecting exons 1-2 of CYP11B1 and 3-9 of CYP11B2. Patient was started on treatment with fludrocortisone 0.1 mg/day and sodium chloride, however required escalating fludrocortisone doses up to 0.5 mg/day. CONCLUSION: We present a case of autosomal recessive ASD in a patient with two novel variants in the CYP11B2 gene. Although laboratory evaluation did not initially demonstrate hyperreninemic hypoaldosteronism, duo rWGS aided in early diagnosis of ASD while expanding the spectrum of likely disease-causing variants. Additionally, to the best of our knowledge, we present one of the first reports of a diagnosis of ASD in an individual of Hispanic origin. Presentation: Sunday, July 13, 2025