Analysis for variable manifestations and molecular characteristics of pyridox(am)ine-5′-phosphate oxidase (PNPO) deficiency

Abstract

Abstract Background To summarize the clinical and genetic characteristics of patients with pyridox(am)ine-5′-phosphate oxidase (PNPO) deficiency. Methods Clinical and genetic data of the patients were collected and analyzed. Results Eighteen patients from 17 families with variants in PNPO were collected, and 15 cases survived to date. The age of onset ranged from 1 day to 5 months (median age 6.5 days) and seven of them presented with seizures <24 h. About 7/18 (39%) of patients showed seizure-free with pyridoxine (PN) or pyridoxal-5′-phosphate treatment. Two patients showed surprised therapeutic responses to antiseizure medications therapy: one could be controlled for up to 1 year and 5 months, and the other showed seizure-free for >8 years. The neurodevelopment was normal in one patient, mild delay in four, in whom responded well to PN. Severe delay could be seen in the remaining 10 surviving patients. Genetic analysis revealed 14 variants of PNPO, seven of which were novel. Five pairs of unrelated patients were observed to carry the same variants, respectively, and had similar developmental status and onset age of seizures in some degree in each pair, whereas also had differences. Conclusions The clinical characteristics, including age of onset, treatment response and prognosis, were variable and difficult to classify into different types clearly. Patients with PNPO deficiency who used PN as their main treatment and being able to control seizures seemed to be associated with better outcomes. Patients with the same genotype tended to show the correlation of phenotype–genotype.