Clinical Variation and Neuroimaging Patterns in Monozygotic Twins With Arrested X-Linked Adrenoleukodystrophy: A Case...

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder leading to neural and adrenal tissue deposition of very long-chain fatty acids. We report 23-year-old monozygotic twins who presented with neuropsychiatric concerns, fatigue, gait difficulty, lower extremity muscle stiffness, and urinary and bowel incontinence. One twin reported difficulty with concentration and mood and had more advanced difficulty with gait and incontinence as compared to his brother. Neurological examination identified weakness in proximal lower extremity muscles, hyperactive deep tendon reflexes in all extremities, positive Babinski sign, and spastic gait of differing severity between the patients. Magnetic resonance imaging (MRI) of the brain revealed T2 hyperintensity in the splenium of the corpus callosum in each subject. MRI of the spine revealed a normal signal in the cord; however, the thoracic segment was asymmetrically atrophied. No pathological enhancement was appreciated. Further testing revealed primary adrenal insufficiency and elevated hexacosanoic acid. Genetic testing confirmed a pathogenic variant in the ABCD1 gene (c.796G>A (p. Gly266Arg), hemizygous). Neurological follow-up has revealed a persistent difference in symptom severity between the patients, which does not correlate with imaging findings or other biomarkers, despite the patients having the same mutation. Two previous reports of monozygotic twins with ALD were notable for progressive cerebral demyelination in only one patient of each pair. This report is unique in describing clinical and imaging variability in arrested cerebral ALD in these identical twins, underscoring the role of suspected non-genomic factors involved in the pathogenesis of this symptomatically diverse entity.