Acute Flaccid Paralysis as Initial Symptom in 4 Patients with Novel E1α Mutations of the Pyruvate Dehydrogenase Complex

Abstract

We report on 4 boys from 3 families presenting initially in infancy with an acute onset of flaccid tetraparesis and areflexia, resembling Guillain-Barré syndrome (GBS). However, the cerebrospinal fluid (CSF) protein was normal, while serum and CSF lactate were elevated. All patients had recurrent similar episodes, usually associated with infections. Brain MRI showed T (2) hyperintensities in the basal ganglia in two boys, in one of them at the first clinical presentation; the other one had a normal brain MRI during the first episode. A third boy had a normal MRI twice but an increased lactate peak in the basal ganglia in (1)H-MR spectroscopy. Motor nerve conduction velocities (NCV) were normal in all patients. Biochemical analyses of muscle tissue, performed in two patients, revealed a deficiency of the pyruvate dehydrogenase (PDH). Molecular genetic analysis of the X-chromosomal E1alpha subunit of PDH showed three new mutations in phylogenetically conserved areas of the protein: Glu358Lys in patient 1; Arg88Lys in patient 2 and 3 (brothers); and Leu216Ser in patient 4. In conclusion, children with "atypical GBS" should be evaluated for a mitochondrial disorder, including pyruvate dehydrogenase deficiency, even after a first episode.

The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients

“…Males slightly outnumbered females and consanguinity accounted for about 7% of all cases. A majority of patients with a deficiency of E1β [137, 157, 163], E2 [142] or E3BP [62, 82, 131, 133, 140, 146, 149] were products of consanguinity, in which the disease often occurred in more than one family member.…”

Disorders of pyruvate metabolism

“…A few patients have developed an acute peripheral neuropathy during infancy (Strassburg et al, 2006) or an acute episodic ataxia (Debray et al, 2008), some without cognitive decline. A few patients have developed an acute peripheral neuropathy during infancy (Strassburg et al, 2006) or an acute episodic ataxia (Debray et al, 2008), some without cognitive decline.…”

Pyruvate Dehydrogenase-E1α Deficiency Presenting as Recurrent Demyelination: An Unusual Presentation and a Novel Mutation

“…A subset of PDH-deficient patients present with an atypical course with intermittent neurological symptoms often triggered by infectious illnesses, like intermittent ataxia (Debray et al 2008), recurrent acute dystonia (Head et al 2004), extrapyramidal movement disorders, and episodic peripheral weakness mimicking Guillain-Barré syndrome (GBS) (Strassburg et al 2006;Debray et al 2006). Such an early initial presentation of PDH deficiency clinically mimicking GBS is quite rare.…”