Phenotypic and molecular spectrum of pyridoxamine-5'-phosphate oxidase (PNPO) deficiency: a scoping review of 87 cases of PNPO deficiency.

Malak Alghamdi, Fahad A Bashiri, Marwa Abdelhakim, Nouran Adly, Dima Z Jamjoom, Khalid M Sumaily, Bandar Alghanem, Stefan T. Arold

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21 Scopus citations


Pyridoxamine-5'-phosphate oxidase (PNPO) deficiency is an autosomal recessive PLP-vitamin-responsive epileptic encephalopathy. The emerging feature of PNPO deficiency is the occurrence of refractory seizures in the first year of life. Prematurity and fetal distress, combined with neonatal seizures, are other associated key characteristics. The phenotype results from a dependency of pyridoxal 5'-phosphate (PLP) which regulates several enzymes in the body. We present the phenotypic and genotypic spectrum of (PNPO) deficiency based on a literature review (2002 to 2020) of reports (n = 33) of patients with confirmed PNPO deficiency (n = 87). All patients who received PLP (n = 36) showed a clinical response, with a complete dramatic PLP response with seizure cessation observed in 61% of patients. In spite of effective seizure control with PLP, approximately 56% of patients affected with PLP-dependent epilepsy suffer developmental delay/intellectual disability. There is no diagnostic biomarker, and molecular testing required for diagnosis. However, we noted that cerebrospinal fluid (CSF) PLP was low in 81%, CSF glycine was high in 80% and urinary VLA was high in 91% of the cases. We observed only a weak correlation between the severity of PNPO protein disruption and disease outcomes, indicating the importance of other factors, including seizure onset and time of therapy initiation. We found that prematurity, the delay in initiation of PLP therapy and early onset of seizures correlate with a poor neurocognitive outcome. Given the amenability of PNPO to PLP therapy for seizure control, early diagnosis is essential. This article is protected by copyright. All rights reserved.
Original languageEnglish (US)
JournalClinical Genetics
StatePublished - Sep 5 2020


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