ClinVar

In 8 patients from 6 unrelated families with pyridoxamine 5-prime-phosphate oxidase deficiency (PNPOD; 610090), Plecko et al. (2014) identified a homozygous c.674G-A transition (c.674G-A, NM_001182.3) in exon 7 of the PNPO gene, resulting in an arg225-to-his (R225H) substitution at a conserved region in the PLP binding site. The mutation, which segregated with the disorder in the families, was not found in 100 control alleles. In vitro functional expression studies in CHO cells showed that the R225H mutant protein had no detectable enzyme activity. Most of the patients had a partial or even complete response to pyridoxine treatment. The 6 families derived from the former Yugoslavia.

In a 7-year-old Greek boy with PNPOD, Ware et al. (2014) identified a homozygous R225 substitution in the PNPO gene. Each unaffected parent was heterozygous for the mutation. Functional studies of the variant were not performed. The patient showed an initial response to treatment with pyridoxine, and later showed a sustained therapeutic response to monotherapy with high-dose pyridoxal 5-prime phosphate (PLP). Ware et al. (2014) hypothesized that some degree of pyridoxine 5-prime-phosphate binding was preserved in the mutant protein, resulting in pyridoxine responsiveness.