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Partial Pyridoxine Responsiveness in PNPO Deficiency
Phillip L Pearl1,2, Keith Hyland3, J Chiles3
1Department of Neurology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC, USA. ppearl@childrensnational.org.
JIMD Reports
|February 23, 2013
Summary
Partial PNPO deficiency can cause epilepsy responsive to vitamin B6. This case shows a transient response to pyridoxine and identifies a CSF metabolite peak, suggesting PNPO deficiency in epilepsy patients.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Autosomal-recessive pyridox(am)ine phosphate oxidase (PNPO) deficiency is a cause of pyridoxal-5-phosphate (PLP)-dependent epilepsy.
- Partial PNPO deficiency may present with unique clinical and biochemical features.
Purpose of the Study:
- To describe a case of partial PNPO deficiency with a transient response to pyridoxine (vitamin B6).
- To identify potential biomarkers for PNPO deficiency in cerebrospinal fluid (CSF).
Main Methods:
- Analysis of CSF neurotransmitter metabolites, PLP, and amino acids during pyridoxine treatment.
- PNPO gene sequencing to identify causative mutations.
- Clinical assessment of seizure control and developmental outcomes.
Main Results:
- A neonate with refractory seizures showed a temporary response to pyridoxine, followed by breakthrough seizures.
- Subsequent administration of PLP controlled seizures, with episodes correlating with dosing intervals.
- PNPO gene sequencing revealed a homozygous mutation (c.352G>A p.G118R) in a conserved region.
- A distinct CSF metabolite peak, potentially pyridoxine phosphate, was observed in the patient.
Conclusions:
- Transient pyridoxine responsiveness can be a feature of partial PNPO deficiency.
- A specific CSF metabolite peak may aid in diagnosing PNPO deficiency in patients on pyridoxine supplementation.
- Partial vitamin B6 responsiveness warrants consideration for PNPO deficiency and a trial of PLP.
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