ABCD1-Related Disease Presenting as an Upper Motor Neuron-Predominant Amyotrophic Lateral Sclerosis Mimic in a Colombian Female Heterozygote: A Case Report.

We report the case of a 47-year-old Colombian woman with a persistent gait disorder beginning at 46 years of age. Neurological examination showed preserved strength, lower-limb spasticity, diffuse hyperreflexia, brisk jaw jerk, and a unilateral Hoffmann sign, without definite bulbar, respiratory, cognitive, sensory, or cerebellar involvement. Brain MRI showed nonspecific occipital/subcortical T2/FLAIR (fluid-attenuated inversion recovery) white matter hyperintensities, and spinal MRI showed mild degenerative changes without compressive myelopathy or spinal cord signal abnormality. Laboratory evaluation did not identify an inflammatory, infectious, nutritional, metabolic, or endocrine cause of myelopathy. Two electrodiagnostic studies showed preserved motor and sensory nerve conduction, normal late responses, normal motor unit action potentials on needle electromyography, and no evidence of active denervation. Neuromuscular ultrasound was also normal, without nerve enlargement, abnormal muscle echogenicity, atrophy, or fasciculations. Overall, there was no diffuse, progressive, multiregional lower motor neuron pattern, and Gold Coast criteria for amyotrophic lateral sclerosis were not fulfilled. A motor neuron disease gene panel identified a heterozygous pathogenic ABCD1 variant, c.1415_1416delAG, p.Gln472Argfs*83. Repeat expansion testing for C9ORF72, ATXN1, and ATXN2 was normal. Classical plasma very-long-chain and branched-chain fatty acid testing showed elevated C26:0 and increased C24:0/C22:0 and C26:0/C22:0 ratios, with normal phytanic and pristanic acids. The clinical, imaging, electrodiagnostic, biochemical, and molecular findings supported ABCD1-related disease with an adrenomyeloneuropathy-predominant phenotype as the most likely explanation for this upper motor neuron-predominant amyotrophic lateral sclerosis (ALS) mimic. This case highlights the importance of considering ABCD1-related disease in adult women with unexplained noncompressive upper motor neuron syndromes when electrodiagnostic studies do not support ALS.