RESUMO
Objective To analyze the clinical characteristics and pyridox (am)ine-5'-phosphate oxidase(PNPO) gene mutations in 2 patients with PNPO deficiency.Methods The identical twin brothers were diagnosed at the Department of Pediatrics of Peking University First Hospital in February 2016.The clinical presentations,course of treatment,blood biochemistry,metabolic screening,EEG,brain magnetic resonance imaging (MRI) and epilepsy-related genes detection (including PNPO gene) of them were analyzed.Results These 2 patients were born at 35 +5weeks gestation and had asphyxia after birth.The seizures started within the first day,which was uncontrolled by various antiepileptic drugs.EEG showed atypical hypsarrhythmia or multifocal epileptiform discharges.MRI showed nonspecific abnormality.Pyridoxine was used as monotherapy or combination with various antiepileptic drugs during the treatment.Seizures had ever been controlled by pyridoxine alone for up to 1 month.Antiepileptic drugs were withdrawn gradually under the circumstances of seizures persisting when they became 5 years old.During the past year,pyridoxine was used alone.They still had seizures at their age of 6 years and 4 months.Blood metabolic screening showed that the level of arginine,asparaginic acid and methionine decreased.Urinary metabolic screening showed vanillic acid elevating prominently in both patients,49.78 and 36.60 times beyond normal,respectively.Genetic analysis showed compound heterozygous variants ofPNPO gene in both patients:c.445_448del (p.P150RfsX27) and c.481C ＞T (p.R161C).These 2variants were not reported previously.After definite diagnosis was made,pyridoxine was replaced by pyridoxal-5'-phosphate (PLP) immediately.Seizures increased slightly at the initial treating with PLP,then reduced gradually and were controlled eventually.Psychomotor development was severely delayed in 2 patients.Conclusions Infantile onset intractable seizures in these 2 patients responded to pyridoxine.The results of blood and urinary metabolic screening suggest the possibility of PNPO deficiency.This is the first time to report patients with PNPO deficiency diagnosed by PNPO gene mutations in China.Seizures could be controlled by PLP monotherapy eventually.