MON-461 X-linked Adrenoleukodystrophy With Mild Imaging And Combined Phenotype In A Family With A Pathogenic ABCD1 Variant

Abstract Disclosure: O.A. Velasco-Espinosa: None. A. Rocha-Haro: None. R. Flores-Cárdenas: None. D. Cuevas-Ramos: None. Background: Adrenoleukodystrophy (ALD) is a rare X-linked disorder caused by mutations in the ABCD1 gene, leading to the toxic accumulation of very long-chain fatty acids (VLCFAs) in the nervous system and adrenal glands. Adrenal insufficiency is a common manifestation, often presenting subtly, even without typical MRI abnormalities, making early diagnosis crucial for management. Clinical Case: A 32-year-old man with a strong family history of ALD presented at age 17 with seizures, which progressed to spastic paraparesis, urinary incontinence, and mild cognitive impairment. Biochemical testing revealed elevated VLCFA levels and adrenal insufficiency. Genetic analysis identified a novel hemizygous mutation in the ABCD1 gene (c.668_669del, p.Ala223Glyfs*77), which was also identified in three family members, including the patient. Brain MRI showed only mild occipital periventricular hyperintensities (Loes score 2), while spinal MRI revealed thoracic cord atrophy. The patient underwent hematopoietic stem cell transplantation (HSCT) from an HLA-matched unrelated donor. Post-transplant, he experienced complications including febrile episodes, cutaneous and systemic graft-versus-host disease (GvHD), adrenal crisis, and infections (CMV, HSV, and E. coli). Seizure frequency decreased with adjustments to antiepileptic therapy and Immunosuppressive therapy was adjusted as needed.At one year post-HSCT, the patient remained clinically stable with no new seizures or radiological progression. Immunosuppression was successfully tapered. Due to ongoing corticosteroid therapy, adrenal function could not be re-evaluated. Chronic oral lichenoid stomatitis persisted. Conclusions: This case highlights the variable and often subtle presentation of ALD, even within families, emphasizing the importance of early diagnosis and genetic testing. Timely HSCT can help stabilize disease progression, though careful multidisciplinary management, particularly with respect to adrenal function and immunosuppressive therapy, is crucial given the risks of complications, including adrenal crisis and graft-versus-host disease. Presentation: Monday, July 14, 2025