Late-onset neurological manifestations of X-linked adrenoleukodystrophy in a male with childhood-onset Addison’s disease: A case report

BACKGROUND Primary adrenal insufficiency [Addison’s disease (AD)] is a rare but potentially life-threatening endocrine disorder caused by impaired cortisol and aldosterone production. While autoimmune adrenalitis is the most common etiology in adults, genetic causes account for a substantial proportion of childhood-onset cases and should be actively investigated. Among inherited etiologies, X-linked adrenoleukodystrophy (X-ALD) is one of the most important genetic causes of primary adrenal insufficiency in males. X-ALD is a peroxisomal disorder caused by pathogenic variants in the ABCD1 gene, leading to impaired degradation of very long-chain fatty acids. Its clinical spectrum ranges from isolated adrenal insufficiency to progressive cerebral demyelination or adrenomyeloneuropathy. CASE SUMMARY We report a 27-year-old male diagnosed with AD in early childhood who remained neurologically asymptomatic for more than two decades, consistent with the so-called “Addison-only” phenotype. In adulthood, he developed progressive psychiatric and neurological manifestations, including behavioral changes and motor symptoms, prompting further evaluation. CONCLUSION This case illustrates that childhood-onset AD in males may represent the earliest manifestation of X-ALD and that the “Addison-only” phenotype does not confer long-term neurological protection. The late emergence of psychiatric and neurological symptoms underscores the need for systematic screening for X-ALD in males with idiopathic early-onset adrenal insufficiency and highlights the importance of lifelong neurological surveillance to avoid delayed diagnosis.