Acute axonal neuropathy in maple syrup urine disease

Kleopa, Kleopas A.; Raizen, David M.; Friedrich, Christopher A.; Brown, Mark J.; Bird, Shawn J.

doi:10.1002/1097-4598(200102)24:2<284::aid-mus140>3.0.co;2-u

Cited by 10 publications

(4 citation statements)

References 17 publications

(18 reference statements)

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“…Indeed, myelination differences are frequently observed in MSUD patients on magnetic resonance imaging (MRI) scans [ 56 , 57 , 58 , 59 , 60 , 61 ]. Additional evidence from histological and electrophysiological data also demonstrated myelin destruction and axonal degeneration in a MSUD case [ 62 ]. Since the destruction of myelin integrity may be involved in the pathogenesis of depression (reviewed in [ 63 ]) and ADHD (reviewed in [ 64 ]), the lower NAA concentrations in MSUD may influence myelin sheath and correlate to the higher severity of depression and ADHD symptoms in MSUD patients.…”

Section: Potential Impacts Of Decreased Brain N-acetylaspartate Anmentioning

confidence: 99%

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

Jakher

Ahrens‐Nicklas

2020

IJMS

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Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), which catalyzes the irreversible catabolism of branched-chain amino acids (BCAAs). Current management of this BCAA dyshomeostasis consists of dietary restriction of BCAAs and liver transplantation, which aims to partially restore functional BCKDC activity in the periphery. These treatments improve the circulating levels of BCAAs and significantly increase survival rates in MSUD patients. However, significant cognitive and psychiatric morbidities remain. Specifically, patients are at a higher lifetime risk for cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorder. Recent literature suggests that the neurological sequelae may be due to the brain-specific roles of BCAAs. This review will focus on the derangements of BCAAs observed in the brain of MSUD patients and will explore the potential mechanisms driving neurologic dysfunction. Finally, we will discuss recent evidence that implicates the relevance of BCAA metabolism in other neurological disorders. An understanding of the role of BCAAs in the central nervous system may facilitate future identification of novel therapeutic approaches in MSUD and a broad range of neurological disorders.

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Section: Potential Impacts Of Decreased Brain N-acetylaspartate Anmentioning

confidence: 99%

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

Jakher

Ahrens‐Nicklas

2020

IJMS

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“…Maple syrup urine disease has been reported as a cause of an acute axonal neuropathy mimicking Guillain-Barré syndrome and is treated with dietary reduction of protein intake w105. Thiamine metabolism dysfunction syndrome 4 is a condition characterised by a progressive chronic axonal neuropathy superimposed by episodes of acute encephalopathy and paralysis following a febrile illness.…”

Section: Introductionmentioning

confidence: 99%

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis

Rossor

Carr

Devine

et al. 2017

J Neurol Neurosurg Psychiatry

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Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy e.g. spasticity, the type of neuropathy, and the other neurological and nonneurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories -1) ataxia, 2) spasticity, and 3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy e.g. cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain Barré syndrome, as many will have a metabolic aetiology and be potentially treatable.

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“…In the present case the cause of the neuropathy is unclear as the BCCA levels normalized quickly. Acute axonal neuropathy complicating classic MSUD has been described in a 25-year-old following decompensation, associated with mild hyponatraemia (Kleopa et al 2001). Also, subclinical chronic peripheral neuropathy consisting of slightly reduced sensory conduction velocities has been reported in children with classic MSUD (Muller et al 1993).…”

Section: Discussionmentioning

confidence: 99%

“…It has been hypothesized that elevated !-ketoisocaproate might inhibit the pyruvate dehydrogenase complex causing the neuropathy (Kleopa et al 2001), and acute neuropathy is well recognized in pyruvate dehydrogenase deficiency (Debray et al 2006). Pyruvate has also been shown to inhibit BCAA oxidation in muscle (Buse et al 1972) and BCKA and BCAA have been shown to inhibit mitochondrial respiratory chain activity and ketoisocaproate to strongly inhibit pyruvate dehydrogenase activity in the brain of young rats (Ribeiro et al 2008;Sgaravatti et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Sensory‐motor polyneuropathy occurring in variant maple syrup urine disease

Harty

King

McCoy

et al. 2008

J of Inher Metab Disea

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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.

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Acute axonal neuropathy in maple syrup urine disease

Cited by 10 publications

References 17 publications

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis

Sensory‐motor polyneuropathy occurring in variant maple syrup urine disease

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