Intermittent peripheral weakness as the presenting feature of pyruvate dehydrogenase deficiency

Abstract

Two unrelated children presenting with episodic isolated peripheral weakness were found to have pyruvate dehydrogenase (PDH) deficiency (OMIM 312170) due to previously undescribed mutations (Pro250Thr, Arg88Cys) in the gene for the E1alpha subunit (PDHA1). Taken in context with the literature, these patients suggest that acute weakness initially resembling Guillain-Barré syndrome is a potentially reversible and probably underdiagnosed manifestation of PDH deficiency and that peripheral nerve function should be evaluated in PDH-deficient patients.

Thiamine responsive pyruvate dehydrogenase deficiency in an adult with peripheral neuropathy and optic neuropathy

“…Very few adults with PDHc deficiency have been described to date (see for examples Robinson,1 Debray and colleagues3 and Mellick and colleagues4). Most had episodes of ataxia, confusion, muscle weakness or hyperventilation triggered by high sugar intake or fever since childhood 1 2.…”

“…Most had episodes of ataxia, confusion, muscle weakness or hyperventilation triggered by high sugar intake or fever since childhood 1 2. Rare cases with adult onset progressive movement disorders (chorea, parkinsonism), cognitive deficit and bilateral necrotic lesions of the putamina and pallidum were also reported 3. Optic neuropathy is a classical feature of energy metabolism disorders.…”

Long-term Outcome and Clinical Spectrum of 73 Pediatric Patients With Mitochondrial Diseases

“…In the intermittent neurologic group, 2 patients with PDH deficiency experienced recurrent episodes of isolated peripheral weakness, initially mimicking Guillain-Barré syndrome. 24 Acute neurologic events were common: 19 patients (26%) experienced neurologic crisis corresponding to stroke-like episodes (6 cases) or Leigh syndrome (13 cases). In addition, 3 other patients had recurrent episodes of severe muscle cramp with or without myoglobinuria, 2 had intermittent ataxia, and 2 others, intermittent peripheral weakness (see above).…”

Sensory‐motor polyneuropathy occurring in variant maple syrup urine disease

“…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).…”