A girl aged 20 months with hyperprolinemia type II, presenting with three convulsions within 15 hours precipitated by pneumonia, was evaluated at Southampton General Hospital, UK. She developed encephalopathy with back arching and purposeless movements. EEGs at first showed slow activity and later, generalized high voltage slow waves with sharp waves and spikes. Brain CT was normal. Urine analysis showed amino acid and organic acid abnormalities consistent with hyperprolinemia type II, and also xanthurenic acid and a metabolite of kynurenine, suggestive of vitamin B6 deficiency. Plasma analyses showed low levels of pyridoxal phosphate and pyridoxic acid, the end product of vitamin B6 catabolism. After 5 weeks of 50 mg pyridoxine/day orally, urine xanthurenic acid levels were normal. Pyrroline-5-carboxylate that accumulates in hyperprolinemia type II may link covalently with and inactivate vitamin B6. Maintenance treatment with vitamin B6 (10 mg/day), advised on discharge, was discontinued at home, and the child was readmitted with encephalopathy and seizures at 4 years of age. After IV pyridoxine 110 mg in divided doses, she recovered within 16 hours and was discharged in 36 hours, to continue daily oral vitamin B6 up to at least 10 years of age. Prior to the first admission, the only illness was a febrile seizure at 18 months, and after discharge she had developed a severe skin rash for 4 weeks in the diaper area. [1]

COMMENT. Hyperprolinemia type II is a rare autosomal recessive disorder caused by a deficiency of D-pyrroline-5-carboxylate dehyrogenase. It presents in childhood with convulsions, precipitated by infection, and sometimes a rash. Plasma analyses show a 10-fold increase in proline, pyrroline-5-carboxylate accumulation, and increased urinary proline, hydroxyproline, and glycine. The vitamin B6 deficiency diagnosed in the above case might account for seizures with hyperprolinemia. Vitamin B6 is inactivated by the proline metabolite pyrroline-5-carboxylate that accumulates in hyperprolinemia type II.