Phenotypic and molecular spectrum of pyridoxamine-5'-phosphate oxidase deficiency: A scoping review of 87 cases of pyridoxamine-5'-phosphate oxidase deficiency.,Clinical Genetics

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Phenotypic and molecular spectrum of pyridoxamine-5'-phosphate oxidase deficiency: A scoping review of 87 cases of pyridoxamine-5'-phosphate oxidase deficiency.
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-09-04 , DOI: 10.1111/cge.13843
Malak Alghamdi _{1,

2} , Fahad A Bashiri _{2,

3} , Marwa Abdelhakim ₄ , Nouran Adly ₅ , Dima Z Jamjoom ₆ , Khalid M Sumaily ₇ , Bandar Alghanem ₈ , Stefan T Arold _{9,

10}

Affiliation

Medical Genetics Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Pediatrics, King Saud University Medical City, Riyadh, Saudi Arabia.
Neurology division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Computer, Electrical and Mathematical Science and Engineering Division (CEMSE), Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
College of Medicine Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Radiology and Medical Imaging, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Clinical Biochemistry Unit, Department of Laboratory Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.
Medical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical, Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King, Abdulaziz Medical City (KAMC), NGHA, Riyadh, Saudi Arabia.
Computational Bioscience, Research Center (CBRC); Division of Biological and Environmental Sciences and Engineering, (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Centre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, Montpellier, France.

Pyridoxamine‐5′‐phosphate oxidase (PNPO) deficiency is an autosomal recessive pyridoxal 5′‐phosphate (PLP)‐vitamin‐responsive epileptic encephalopathy. The emerging feature of PNPO deficiency is the occurrence of refractory seizures in the first year of life. Pre‐maturity and fetal distress, combined with neonatal seizures, are other associated key characteristics. The phenotype results from a dependency of PLP which regulates several enzymes in the body. We present the phenotypic and genotypic spectrum of (PNPO) deficiency based on a literature review (2002‐2020) 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 vanillactic acid 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 pre‐maturity, 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.

中文翻译：

吡哆胺-5'-磷酸氧化酶缺乏症的表型和分子谱：87例吡哆胺-5'-磷酸氧化酶缺乏症的范围综述。

吡哆胺-5'-磷酸氧化酶（PNPO）缺乏症是一种常染色体隐性遗传的5'-磷酸吡哆醛（PLP）-维生素反应性癫痫性脑病。PNPO 缺乏症的新特征是在生命的第一年发生难治性癫痫发作。早产和胎儿窘迫以及新生儿癫痫发作是其他相关的关键特征。该表型是由 PLP 的依赖性引起的，PLP 调节体内的几种酶。我们根据对确诊的 PNPO 缺乏症（n = 87）患者报告（n = 33）的文献综述（2002-2020），介绍了 (PNPO) 缺乏症的表型和基因型谱。所有接受 PLP 的患者（n = 36）均显示出临床反应，在 61% 的患者中观察到完全显着的 PLP 反应和癫痫发作停止。尽管 PLP 能有效控制癫痫发作，大约 56% 的 PLP 依赖性癫痫患者患有发育迟缓/智力障碍。没有诊断生物标志物，也不需要诊断所需的分子检测。然而，我们注意到 81% 的脑脊液 (CSF) PLP 低，80% 的脑脊液甘氨酸高，91% 的病例尿香草酸高。我们观察到 PNPO 蛋白破坏的严重程度与疾病结果之间仅存在微弱的相关性，表明其他因素的重要性，包括癫痫发作和治疗开始时间。我们发现早产、延迟开始 PLP 治疗和早期癫痫发作与较差的神经认知结果相关。鉴于 PNPO 适合 PLP 治疗以控制癫痫发作，早期诊断至关重要。

更新日期：2020-09-04

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