MON-460 Primary Adrenal Insufficiency Resulting in Diagnosis of Rare ABCD1 Mutation in X-linked Adrenoleukodystrophy

Abstract Disclosure: A. Jin: None. A. Bryant: None. A. Bhatnagar: None. K. Soe: None. X-linked adrenoleukodystrophy (X-ALD) is a rare congenital neurodegenerative demyelinating disorder and primary adrenal insufficiency with variable presentations. The diagnosis can be delayed and easily missed especially among adults. We report a case of a 32-year-old African American male with adult-onset X-ALD presenting with primary adrenal insufficiency only and Marfanoid features. He was diagnosed with primary adrenal insufficiency of unknown etiology at the age of 22 when he was hospitalized with generalized weakness, dehydration and acute renal failure. He was able to maintain normal blood pressure and functionality by taking hydrocortisone only without fludrocortisone replacement. The patient was also noted to have marfanoid habitus. Further workup for primary adrenal insufficiency revealed negative 21-alpha-hydroxylase antibodies and elevated Very Long Chain Fatty Acids (VLCFA). Genetic testing showed the novel mutation of ABCD1 gene, p.His97Arg, confirming the diagnosis of X-ALD. Evaluation by ophthalmology, neurology and neuropsychiatry was insignificant, and he was found to have normal cognition and neurological function. MRI of the brain and the entire spine was unremarkable. No genetic testing for Marfanoid features was done, as there were no cardiac and eye findings to support the diagnosis of Marfan syndrome. The patient has no known family members with significant endocrine disorder and X-ALD genetic screening for his family is in progress. This case highlights the importance of considering X-ALD as a potential diagnosis and screening by checking VLCFA in the plasma in male patients with primary adrenal insufficiency without adrenal antibodies. This case is unique in the novel genetic mutation found on testing and association with marfanoid features. Even though X-ALD is rare, it should be considered as a possible etiology for primary adrenal insufficiency because of associated endocrinopathies, neurological deficits, and significant variations in clinical presentation. It is important to raise awareness among providers that diagnosis with measurement of VLCFA is commercially available. It is crucial to counsel patients that diagnosis can be difficult due to limitations in currently available genetic testing methodology, lack of genotype to phenotype correlation, and the possibility of unknown genetic variants with unpredictable prognosis and clinical course. It is imperative that this rare but consequential diagnosis be kept on the differential so that patients are offered appropriate testing and referrals for life or family planning. Though there is no definitive treatment apart from steroid supplementation in adrenal insufficiency and monitoring, patients should be counseled on sick day rules for steroids, medical alert bracelets for adrenal insufficiency, and hydrocortisone administration in emergencies, which may be life-saving. Presentation: Monday, July 14, 2025