We report the case of an 8-year-old boy with
pyridoxamine 5'-phosphate
oxidase (
PNPO) deficiency. He developed
seizures at 24 h of age that were refractory to standard
anticonvulsant therapy and a trial of
pyridoxine but responded to
pyridoxal phosphate (PLP) at 28 days of life. Genetic testing identified compound heterozygous mutations in the PNPO gene. Management of encephalopathic episodes required escalation of PLP dose to 100 mg/kg/day by 2 years of age. Routine blood tests at this time showed significantly deranged liver function tests (LFTs). A wedge liver biopsy showed early
cirrhosis with marked elevation of
pyridoxal and
pyridoxic acid levels in the liver sample. Despite extensive investigation, no cause other than PLP
therapy could be identified for the
cirrhosis. The PLP dose was weaned to 50 mg/kg/day before episodes of
encephalopathy recurred. Concurrent with the reduction of his PLP dose, LFTs showed improvement. However, at 8 years of age, there is persistent evidence of hepatic
fibrosis and early
portal hypertension. We hypothesise that hepatic toxicity due to PLP or its degradation products is the cause of
cirrhosis in this boy. Until further evidence becomes available, we would suggest that people with
PNPO deficiency are treated with the minimum dose of PLP required to prevent episodes of
encephalopathy.