Normal Neurodevelopmental Outcomes in PNPO Deficiency: A Case Series and Literature Review

Abstract

Pyridox(am)ine 5 0 -phosphate oxidase deficiency results in an early-onset neonatal encephalopathy that can be fatal if not detected and treated early. The condition is rare, can result in preterm delivery, and can mimic hypoxic ischemic encephalopathy. Thus, suspicion of the diagnosis, appropriate investigations, and therapeutic trials with pyridoxal-5 0 -phosphate are often delayed. In this paper we report four cases of pyridox(am)ine 5 0 -phosphate oxidase deficiency, two of whom are siblings. Three were treated with pyridoxal-5 0 -phosphate in the first few days of life and the fourth within the first month. One of the siblings was electively treated from birth until a diagnosis was secured. Our cases demonstrate that early diagnosis and treatment can be associated with normal neurodevelopment in childhood. We suggest that a low threshold for investigating for pyridox(am)ine 5 0 -phosphate oxidase deficiency and electively treating with pyridoxal-5 0 -phosphate is considered in any neonate with encephalopathy, including those with presumed hypoxic ischemic encephalopathy in whom the degree of encephalopathy is not expected from perinatal history, cord gases and/or neuroimaging.

Disorders affecting vitamin B6 metabolism

“…Treatment of PNPO deficiency was found to be more difficult than that of ALDH7A1 deficiency in that PNPO‐deficient patients may require a dose of PLP every 6 hours to avoid an epileptic prodrome or frank seizures. Reports have emphasized the possibility of normal developmental outcome with early treatment . A summary of the clinical features of patients with PNPO deficiency are as detailed in Figure .…”

“…Reports have emphasized the possibility of normal developmental outcome with early treatment. 86,87 A summary of the clinical features of patients with PNPO deficiency are as detailed in Figure 6.…”

Quality and stability of extemporaneous pyridoxal phosphate preparations used in the treatment of paediatric epilepsy

“…This disorder is characterised by drug‐resistant seizures that can be fatal. Classically, seizures are responsive exclusively to PLP but patients show a good neurodevelopmental outcome when treated promptly . Recently, it has become apparent that in some cases of PNPO deficiency, pyridoxine is an effective treatment .…”

“…Classically, seizures are responsive exclusively to PLP but patients show a good neurodevelopmental outcome when treated promptly. [3][4][5] Recently, it has become apparent that in some cases of PNPO deficiency, pyridoxine is an effective treatment. [6][7][8][9] However, in more than half of the patients, PLP is still the only effective form of treatment.…”

Metabolic Disorders Presenting with Seizures in the Neonatal Period

“…Brain imaging is nonspecific and may be normal. [36][37][38][39][40][41] In the absence of vitamin therapy, there are significant intellectual and developmental disabilities. There is increased mortality associated with prolonged seizures.…”