Sensory-motor polyneuropathy occurring in variant maple syrup urine disease.
Maple syrup urine disease (MSUD; OMIM 248600) results from an inherited deficiency of the branched-chain ketoacid dehydrogenase (BCKD) complex. Approximately 20% of patients with BCKD deficiency are non-classic variants of MSUD with differing clinical severity. Outcomes for this cohort are generally favourable; episodes of metabolic decompensation do not appear to correlate with adverse events if acute management is promptly provided. A case of predominantly axonal sensory-motor neuropathy following metabolic decompensation which persisted for a number of months is presented in an adolescent girl with variant (intermediate type) MSUD. EMG and nerve conduction studies suggested a pre-existent asymptomatic chronic neuropathy, exacerbated by the acute decompensation. Peak leucine concentration at decompensation was 1083 μmol/L. The patient had laboratory signs of secondary mitochondrial respiratory chain dysfunction at presentation. She had been on a moderate dose of thiamine prior to decompensation; thiamine and pyridoxine blood concentrations were normal. This, to our knowledge, is the first report of a neuropathy presenting in a patient with a decompensation of variant MSUD. We propose that this presentation resembles the intermittent neuropathy observed in pyruvate dehydrogenase deficiency and may reflect secondary inhibition of pyruvate dehydrogenase activity by MSUD metabolites.
National Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple St., Dublin 1, Ireland.
S
S
Harty
M D
MD
King
B
B
McCoy
D
D
Costigan
E P
EP
Treacy
D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004576:Electromyography; D005260:Female; D006801:Humans; D007930:Leucine / Q000097:blood; D008375:Maple Syrup Urine Disease / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D028361:Mitochondrial Diseases / Q000209:etiology / Q000503:physiopathology; D009431:Neural Conduction; D009460:Neurologic Examination; D010525:Peripheral Nerves / Q000503:physiopathology*; D011115:Polyneuropathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D011597:Psychomotor Performance; D012008:Recurrence; D013997:Time Factors
D015415:Biomarkers; D007930:Leucine