FRI252 Novel Mutation Presenting With Hypoaldosteronism In X-Linked Adrenal Hypoplasia Congenita

Abstract Disclosure: E. Ismail: None. L. Jacobsen: None. Background: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder due to a mutation in DAX-1/NR0B1, a nuclear factor that is important for the development and function of the adrenals and reproductive system. It usually presents with adrenal insufficiency in infancy and later hypogonadotropic hypogonadism. Here we describe a patient who presented with a salt wasting crisis due to hypoaldosteronism and genetic testing revealed a novel frameshift mutation in NR0B1/DAX-1 resulting in premature protein termination. Clinical Case: A 4 week old male presented with poor feeding, failure to thrive, hyponatremia, hyperkalemia, and acidosis. No hypoglycemia present. He also had an undetectable aldosterone level, high renin, normal cortisol, high ACTH, and normal 17OHP. Adrenal ultrasound (US) failed to show the right adrenal gland. With suspicion for primary hypoaldosteronism, he was started on salt supplementation and fludrocortisone with improved growth, electrolytes, and renin. His genitalia were that of a typical male infant without cutaneous hyperpigmentation. ACTH level continued to trend up despite appropriate baseline cortisol. Stimulation test with 250 mcg of Cosyntropin was done which revealed suboptimal peak cortisol of 11.5 mcg/dL (normal >18 mcg/dL), so he was started on stress dose precautions of hydrocortisone without physiologic replacement. Repeat US 2 months later did not visualize his adrenals. With suspicion for AHC, genetic testing was obtained which revealed a novel frame shift variant in NR0B1 (c.1069del, p.Gln357Argfs*15, hemizygous), resulting in premature protein termination. He was then started on daily hydrocortisone replacement. As this is an X-linked mutation, genetic testing for mother and older brother is pending. To the best of our knowledge this variant has not been reported in the literature. Conclusion: DAX-1 mutations should be considered in male infants presenting with primary hypoaldosteronism. ACTH stimulation testing is necessary to assess glucocorticoid function, especially if ACTH is elevated, which can precede cortisol deficiency. There is a wide heterogeneity in the presentation of this rare disorder, so genetic diagnosis is important to guide management, later monitoring for hypogonadism and fertility, and family testing. Presentation: Friday, June 16, 2023