Intermittent Maple Syrup Urine Disease Presenting With Chronic Demyelinating Polyneuropathy: A Genetically Confirmed DBT-Related Case.
- 1Division of Neurogenetics and Neuromuscular Disorders, Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil.
- 2Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
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.
Related
- Acute-Onset Chronic Inflammatory Demyelinating Polyneuropathy May Manifest as Recurrent Guillain-Barré Syndrome of a Severe Refractory Case
- Reply to the Letter “Acute-Onset Chronic Inflammatory Demyelinating Polyneuropathy May Manifest as Recurrent Guillain-Barré Syndrome of a Severe Refractory Case”
- Pathophysiology and Emerging Therapies in Chronic Inflammatory Demyelinating Polyneuropathy
- Diagnostic spectrum and clinical outcomes of chronic inflammatory demyelinating polyneuropathy: a multicenter cohort
- Electrophysiological profile of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes syndrome: demyelinating features and lower-limb-predominant response loss
BibTeX
@article{gomes2026intermittent,
title = {{Intermittent Maple Syrup Urine Disease Presenting With Chronic Demyelinating Polyneuropathy: A Genetically Confirmed DBT-Related Case.}},
author = {Gustavo Rodrigues Ferreira Gomes and Antonio Edvan Camelo Filho and Ellen Mourão Soares Lopes and Raquel Diógenes Alencar and Erlane Marques Ribeiro and Kécia Tavares de Oliveira and Paulo Ribeiro Nóbrega and André Luiz Santos Pessoa},
journal = {Journal of the peripheral nervous system : JPNS},
year = {2026},
month = oct,
doi = {10.1111/jns.70176},
url = {https://europepmc.org/article/MED/42907158},
note = {CC BY},
}
RIS
TY - JOUR
TI - Intermittent Maple Syrup Urine Disease Presenting With Chronic Demyelinating Polyneuropathy: A Genetically Confirmed DBT-Related Case.
AU - Gustavo Rodrigues Ferreira Gomes
AU - Antonio Edvan Camelo Filho
AU - Ellen Mourão Soares Lopes
AU - Raquel Diógenes Alencar
AU - Erlane Marques Ribeiro
AU - Kécia Tavares de Oliveira
AU - Paulo Ribeiro Nóbrega
AU - André Luiz Santos Pessoa
PY - 2026
DA - 2026/10/30
JO - Journal of the peripheral nervous system : JPNS
DO - 10.1111/jns.70176
UR - https://europepmc.org/article/MED/42907158
AB - 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.
SN - 1085-9489
SN - 1529-8027
ER -