磷酸吡哆醇(胺)氧化酶缺乏症罕见c.481C > T位点突变1例并文献复习
A Case of Rare Deficiency of Pyridox(am)ine-5’-Phosphate Oxidase c.481C > T Site Mutation with Literature Review
摘要: 目的：对磷酸吡哆醇(胺)氧化酶[pyridox(am)ine-5’-phosphate oxidase, PNPO]缺乏症1例患儿的临床资料进行分析并文献综述，总结PNPO缺乏症的临床特征及致病基因。方法：回顾性分析1例确诊PNPO缺乏的早产儿，并对患儿及父母进行全外显子组基因检测。检索PubMed、Web of Science、中国知网、维普及中华医学期刊全文数据库，总结PNPO缺乏症的临床特点及遗传学病因。结果：患儿为胎龄32周 + 1天早产儿，生后当天出现癫痫发作，脑电图(EEG)提示痫样放电，联合应用多种抗癫痫药物治疗无效。基因检测为c.481C > T PNPO基因纯合突变，该位点的纯合突变为国内首次报道。采用维生素B6单药控制良好，随访6个月体格发育、脑电图。结论：本例PNPO缺乏症为罕见c.481C > T位点PNPO基因突变，表现为生后早期出现难治性癫痫，抗癫痫治疗无效，可被磷酸吡哆醇单药控制，预后良好。
Abstract: Objective: To investigate the clinical data of a child with pyridox(am)ine-5’-phosphate oxidase (PNPO) deficiency with literature review, and summarize the clinical features and pathogenic genes of PNPO deficiency. Methods: A retrospective analysis was conducted on a case of premature infant diagnosed with PNPO deficiency, and whole exome sequencing was performed on the infant and his parents. PubMed, Web of Science, China National Knowledge Infrastructure, VIP, and the Chinese Medical Journal Full-Text Database were searched to summarize the clinical characteristics and genetic causes of PNPO deficiency. Results: The child is a premature infant with a gestational age of 32 weeks + 1 day. On the day of birth, the child experienced seizures, and the electroencephalogram (EEG) indicated epileptiform discharges. Combined treatment with various antiepileptic drugs was ineffective. Genetic monitoring of the child revealed a homozygous mutation in the c.481C > T PNPO gene, which is the first report of such a homozygous mutation in China. The child was well controlled with vitamin B6 monotherapy, and follow-up visits for 6 months were conducted to monitor growth and EEG. Conclusion: The PNPO deficiency in this case is a rare c.481C > T PNPO gene mutation. The child presents with refractory epilepsy in the early postnatal period, and antiepileptic treatment is ineffective. It can be controlled by pyridoxal phosphate monotherapy and has a good prognosis.
文章引用：王郁欣, 姜红. 磷酸吡哆醇(胺)氧化酶缺乏症罕见c.481C > T位点突变1例并文献复习[J]. 临床医学进展, 2025, 15(3): 377-383. https://doi.org/10.12677/acm.2025.153626

参考文献

[1] Mills, P.B., Surtees, R.A.H., Champion, M.P., Beesley, C.E., Dalton, N., Scambler, P.J., et al. (2005) Neonatal Epileptic Encephalopathy Caused by Mutations in the PNPO Gene Encoding Pyridox(am)ine 5’-Phosphate Oxidase. Human Molecular Genetics, 14, 1077-1086. [Google Scholar] [CrossRef] [PubMed]
[2] Guerin, A., Aziz, A.S., Mutch, C., Lewis, J., Go, C.Y. and Mercimek-Mahmutoglu, S. (2014) Pyridox(am)ine-5-Phosphate Oxidase Deficiency Treatable Cause of Neonatal Epileptic Encephalopathy with Burst Suppression. Journal of Child Neurology, 30, 1218-1225. [Google Scholar] [CrossRef] [PubMed]
[3] Veeravigrom, M., Damrongphol, P., Ittiwut, R., Ittiwut, C., Suphapeetiporn, K. and Shotelersuk, V. (2015) Pyridoxal 5’-Phosphate-Responsive Epilepsy with Novel Mutations in the PNPO Gene: A Case Report. Genetics and Molecular Research, 14, 14130-14135. [Google Scholar] [CrossRef] [PubMed]
[4] 朱海霞, 李小晶, 王秀英, 等. 磷酸吡哆醇(胺)氧化酶缺乏症1例报告并文献复习[J]. 癫癎与神经电生理学杂志, 2017, 26(4): 193-196.
[5] Hoffmann, G.F., Schmitt, B., Windfuhr, M., Wagner, N., Strehl, H., Bagci, S., et al. (2006) Pyridoxal 5’‐Phosphate May Be Curative in Early‐Onset Epileptic Encephalopathy. Journal of Inherited Metabolic Disease, 30, 96-99. [Google Scholar] [CrossRef] [PubMed]
[6] Ruiz, A., García-Villoria, J., Ormazabal, A., Zschocke, J., Fiol, M., Navarro-Sastre, A., et al. (2008) A New Fatal Case of Pyridox(am)ine 5’-Phosphate Oxidase (PNPO) Deficiency. Molecular Genetics and Metabolism, 93, 216-218. [Google Scholar] [CrossRef] [PubMed]
[7] Schmitt, B., Baumgartner, M., Mills, P.B., Clayton, P.T., Jakobs, C., Keller, E., et al. (2010) Seizures and Paroxysmal Events: Symptoms Pointing to the Diagnosis of Pyridoxine‐Dependent Epilepsy and Pyridoxine Phosphate Oxidase Deficiency. Developmental Medicine & Child Neurology, 52, e133-e142. [Google Scholar] [CrossRef] [PubMed]
[8] Sudarsanam, A., Singh, H., Wilcken, B., Stormon, M., Arbuckle, S., Schmitt, B., et al. (2014) Cirrhosis Associated with Pyridoxal 5’-Phosphate Treatment of Pyridoxamine 5’-Phosphate Oxidase Deficiency. JIMD Reports, 17, 67-70. [Google Scholar] [CrossRef] [PubMed]
[9] 单媛媛, 周也群, 杨琳, 等. 磷酸吡哆醇(胺)氧化酶基因突变相关新生儿癫痫一例并文献复习[J]. 中国小儿急救医学, 2021, 28(8): 731-733.
[10] Khayat, M., Korman, S.H., Frankel, P., Weintraub, Z., Hershckowitz, S., Sheffer, V.F., et al. (2008) PNPO Deficiency: An under Diagnosed Inborn Error of Pyridoxine Metabolism. Molecular Genetics and Metabolism, 94, 431-434. [Google Scholar] [CrossRef] [PubMed]
[11] Levtova, A., Camuzeaux, S., Laberge, A., Allard, P., Brunel-Guitton, C., Diadori, P., et al. (2015) Normal Cerebrospinal Fluid Pyridoxal 5’-Phosphate Level in a PNPO-Deficient Patient with Neonatal-Onset Epileptic Encephalopathy. JIMD Reports, 22, 67-75. [Google Scholar] [CrossRef] [PubMed]
[12] Bräutigam, C., Hyland, K., Wevers, R., Sharma, R., Wagner, L., Stock, G., et al. (2002) Clinical and Laboratory Findings in Twins with Neonatal Epileptic Encephalopathy Mimicking Aromatic L-Amino Acid Decarboxylase Deficiency. Neuropediatrics, 33, 113-117. [Google Scholar] [CrossRef] [PubMed]
[13] Ware, T.L., Earl, J., Salomons, G.S., Struys, E.A., Peters, H.L., Howell, K.B., et al. (2013) Typical and Atypical Phenotypes of PNPO Deficiency with Elevated CSF and Plasma Pyridoxamine on Treatment. Developmental Medicine & Child Neurology, 56, 498-502. [Google Scholar] [CrossRef] [PubMed]
[14] Plecko, B., Paul, K., Mills, P., Clayton, P., Paschke, E., Maier, O., et al. (2014) Pyridoxine Responsiveness in Novel Mutations of the PNPO Gene. Neurology, 82, 1425-1433. [Google Scholar] [CrossRef] [PubMed]
[15] Jaeger, B., Abeling, N.G., Salomons, G.S., Struys, E.A., Simas-Mendes, M., Geukers, V.G., et al. (2016) Pyridoxine Responsive Epilepsy Caused by a Novel Homozygous PNPO Mutation. Molecular Genetics and Metabolism Reports, 6, 60-63. [Google Scholar] [CrossRef] [PubMed]
[16] Bender, D.A. (1994) Novel Functions of Vitamin B6. Proceedings of the Nutrition Society, 53, 625-630. [Google Scholar] [CrossRef] [PubMed]
[17] Alghamdi, M., Bashiri, F.A., Abdelhakim, M., Adly, N., Jamjoom, D.Z., Sumaily, K.M., et al. (2020) Phenotypic and Molecular Spectrum of Pyridoxamine‐5’‐Phosphate Oxidase Deficiency: A Scoping Review of 87 Cases of Pyridoxamine‐5’‐Phosphate Oxidase Deficiency. Clinical Genetics, 99, 99-110. [Google Scholar] [CrossRef] [PubMed]
[18] Goyal, M., Fequiere, P.R., McGrath, T.M. and Hyland, K. (2013) Seizures with Decreased Levels of Pyridoxal Phosphate in Cerebrospinal Fluid. Pediatric Neurology, 48, 227-231. [Google Scholar] [CrossRef] [PubMed]
[19] Veerapandiyan, A., Winchester, S.A., Gallentine, W.B., Smith, E.C., Kansagra, S., Hyland, K., et al. (2011) Electroencephalographic and Seizure Manifestations of Pyridoxal 5’-Phosphate-Dependent Epilepsy. Epilepsy & Behavior, 20, 494-501. [Google Scholar] [CrossRef] [PubMed]
[20] di Salvo, M.L., Mastrangelo, M., Nogués, I., Tolve, M., Paiardini, A., Carducci, C., et al. (2017) Pyridoxine-5’-Phosphate Oxidase (PNPO) Deficiency: Clinical and Biochemical Alterations Associated with the C.347g > A (P.∙Arg116gln) Mutation. Molecular Genetics and Metabolism, 122, 135-142. [Google Scholar] [CrossRef] [PubMed]
[21] Porri, S., Fluss, J., Plecko, B., Paschke, E., Korff, C. and Kern, I. (2013) Positive Outcome Following Early Diagnosis and Treatment of Pyridoxal-5’-Phosphate Oxidase Deficiency: A Case Report. Neuropediatrics, 45, 064-068. [Google Scholar] [CrossRef] [PubMed]
[22] Mohanlal, S., Bindu, P.S., Sureshbabu, S. and Kumar, S. (2020) Variable Treatment Response in a Patient with Pyridoxal N Phosphate Oxidase (PNPO) Deficiency-Understanding the Paradox. Epilepsy & Behavior Reports, 14, Article ID: 100357. [Google Scholar] [CrossRef] [PubMed]

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