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Wednesday, April 30, 2014

In the March 21st issue of the journal Neurology ahead of press, Dr. Plecko and colleagues representing a European consortium present an analysis to assess whether patients with pyridoxine-responsive seizures with normal biomarkers for a specific deficiency for antiquitin yet normal sequencing of the ALDH7A1 gene may have PNPO mutations.


  • The investigators sequenced the PNPO gene in 31 patients who fulfilled the criteria of having pyridoxine-responsive seizures, but the normal biomarkers for the deficiency.

  • The investigators identified 11 patients carrying 3 novel mutations of the PNPO gene. In 6 families, a homozygous missense mutation – p.Arg225His in exon 7 – was identified, while one family was identified with compound heterozygous for a novel missense mutation p.Arg141Cys in exon 5 and the deletion in C.279290del in exon 3.

  • The response to pyridoxine was prompt in 4; delayed in 2; on EEG only in 2; and initially absent in another 2 patients.

  • Two unrelated patients homozygous for the p.Arg225His mutation experienced status epilepticus when switched to pyridoxal 5’-phosphate (PLP).

  • The investigators concluded that this study challenges the paradigm of exclusive PLP responsiveness in patients with PLP oxidase deficiency and underlines the importance of consecutive testing of pyridoxine and PLP in neonates with anti-epileptic drug resistant seizures.

  • Patients with pyridoxine response but normal biomarkers for antiquitin deficiency should undergo PNPO mutation analysis.

Authored by: Joseph I. Sirven, MD on 4/2014
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