Background: When a patient presents with progressive upper and lower motor neuron findings, a limited number of diagnoses outside of amyotrophic lateral sclerosis (ALS) are considered. Mitochondrial membrane protein-associated neurodegeneration (MPAN), a rare genetic disorder and subtype of neurodegeneration and brain iron accumulation (NBIA), can present with motor neuronopathy and mimic features of ALS.

Case presentation: We report a case of a 27-year-old male with autism diagnosed in childhood, optic atrophy, and two years of progressive gait instability without sensory symptoms. On exam, the patient scored 15/30 on his mini-mental state examination (MMSE). He had mild dysarthria, impaired vertical saccades, and normal visual acuity. He had mild weakness in the distal upper extremities and very mild weakness in proximal lower extremities. He had diffuse hyperreflexia and increased tone, particularly in the lower limbs, and a normal sensory exam. Magnetic resonance imaging (MRI) of the brain showed T2 hypointensities of the bilateral globus pallidus and substanstia nigra and subtle T1 hyperintensities. Full spinal imaging was normal. Nerve conduction studies (NCS) were normal except for a mild right ulnar neuropathy; electromyography (EMG) showed activedenervation changes in both upper and lower limbs with some chronic neurogenicchanges. Whole genome sequencing revealed a heterozygous likely pathogenic variant in the gene C19orf12 (NM_001031726.3 [GRCh37/hg19]: c.257_267del), which causes a frame shift in the protein reading frame. De novo heterozygous truncating variants in exon 3 of C19orf12 have been associated with MPAN and explains this patient’s history, physical exam, and imaging findings.

Discussion: This case highlights the importance of evaluating genetic causes for motor neuronopathy when symptoms mimic ALS and non-neurological symptoms are static. Additionally, this case sheds light on clinical and imaging findings associated with MPAN, a disorder typically diagnosed in childhood but may come to the attention of adult neurologists if overlooked.