Abstract
Pyridox(am)ine 5′-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′-phosphate are often delayed. In this paper we report four cases of pyridox(am)ine 5′-phosphate oxidase deficiency, two of whom are siblings. Three were treated with pyridoxal-5′-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′-phosphate oxidase deficiency and electively treating with pyridoxal-5′-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.
Competing interests: None declared
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Acknowledgements
The authors thank Medical Neurogenetics, Atlanta, for sequencing the PNPO gene in cases 1 and 2. The authors sincerely thank the families of the cases discussed in this paper.
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Communicated by: John Christodoulou, MBBS, PhD, FRACP, FRCPA
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Joshua Hatch, David Coman, Peter Clayton, Philippa Mills, Sophie Calvert, Richard Webster and Kate Riney declare that they have no conflicts of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
Author Contributions
Dr Joshua Hatch has driven the manuscript development.
Professor David Coman is a metabolic physician involved in the care of patients 1–3 and has coordinated the manuscript development and design.
Professor Peter Clayton is a metabolic physician who has provided invaluable clinical advice on all four patients and has been involved in the manuscript development.
Dr Philippa Mills has provided valuable advice regarding the molecular pathogenicity of the mutations identified and has been involved in the manuscript development.
Dr Sophie Calvert is a paediatric neurologist, providing neurology care for case 3, and has been involved in the manuscript development.
Dr Richard Webster is a paediatric neurologist, providing neurology care for case 4, and has been involved in the manuscript development.
Dr Kate Riney is a paediatric neurologist, providing neurology care for cases 1 and 2, and has been involved in the manuscript development.
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Hatch, J. et al. (2015). Normal Neurodevelopmental Outcomes in PNPO Deficiency: A Case Series and Literature Review. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 26. JIMD Reports, vol 26. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_482
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DOI: https://doi.org/10.1007/8904_2015_482
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