Intermittent Maple Syrup Urine Disease Presenting With Chronic Demyelinating Polyneuropathy: A Genetically Confirmed DBT ‐Related Case

Abstract

ABSTRACT Background and Aims Maple syrup urine disease (MSUD) is an inherited disorder of branched‐chain amino acid metabolism caused by deficiency of the branched‐chain α‐keto acid dehydrogenase complex. Neurological manifestations predominantly involve the central nervous system, whereas peripheral nervous system involvement has been rarely reported. Results We report a genetically confirmed case of intermittent MSUD caused by compound heterozygous pathogenic variants in DBT in a female patient who developed recurrent ataxic episodes beginning in early childhood, followed by acute ascending weakness during metabolic decompensation at 12 years of age. Initially suspected to have Guillain–Barré syndrome, subsequent biochemical and molecular investigations established the diagnosis of MSUD. Five years later, despite good metabolic control and substantial functional recovery, follow‐up nerve conduction studies, and electromyography demonstrated a chronic demyelinating sensorimotor polyneuropathy. Clinical examination additionally revealed bilateral pes cavus and persistent mild distal lower‐limb weakness. Interpretation Only a few cases of peripheral neuropathy associated with MSUD have previously been described. Our findings expand the phenotypic spectrum by documenting the longitudinal evolution from recurrent childhood neurological episodes to chronic mixed demyelinating–axonal polyneuropathy. The clinical course supports the hypothesis that repeated metabolic decompensation may contribute to cumulative peripheral nerve injury. Although the precise mechanisms remain uncertain, mitochondrial dysfunction, impaired energy metabolism, oxidative stress, and branched‐chain amino acid and α‐keto acid toxicity provide plausible explanations. Conclusion Peripheral neuropathy should be recognized as a potential manifestation of MSUD, including intermittent phenotypes. Long‐term neurological follow‐up incorporating electrophysiological evaluation may improve recognition of peripheral nervous system involvement and contribute to a more complete characterization of the disease.

The authors' abstract, as published at the source. Journal of the Peripheral Nervous System, 2026 · DOI ↗