Ahmed Sibtain, DeBerardinis Ralph J, Ni Min, Afroze Bushra
Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.
Children's Medical Center Research Institute at UT Southwestern, Texas, USA, Howard Hughes Medical Institute, UT Southwestern Medical Center, USA.
Ann Med Surg (Lond). 2020 Dec 1;60:721-727. doi: 10.1016/j.amsu.2020.11.079. eCollection 2020 Dec.
The Vitamin B6-dependent epilepsies are a heterogeneous group of autosomal recessive disorders usually characterized by neonatal onset seizures responsive to treatment with vitamin B6 available as pyridoxine (PN) or as the biologically active form pyridoxal 5-phosphate (PLP). The vitamin B6-dependent epilepsies are caused by mutations in at least five different genes involved in B6 metabolism. A literature review revealed that only 30 patients with vitamin B6-dependent epilepsy caused by mutation have been reported worldwide.
We report a case of baby boy born to first-cousin Pakistani parents who presented with generalized as well as focal seizures starting a few hours after birth and responsive to PLP. Whole exome sequencing revealed a homozygous pathogenic variant NM_007198.4:c.46_47insCA, NP_009129.1:p.Leu17Hisfs, causing a CA duplication resulting in a frameshift in the gene.
Vitamin B6-Dependent Epilepsy due to defect is a rare disorder. The developmental outcomes are variable even with early therapy. Few patients are reported to achieve optimal developmental milestones with therapy. PLP has been advocated as the treatment of choice for defect, but oral PN has also demonstrated good seizure control in some patients, including ours.
Vitamin B6-dependent epilepsy due to defect is an important differential diagnosis to consider in patients with biochemical features suggestive of pyridoxamine 5'-phosphate Oxidase () defect and gene testing can facilitate in reaching the correct diagnosis. Prompt diagnosis and treatment led to excellent seizure control in most patients.
维生素B6依赖性癫痫是一组常染色体隐性遗传疾病，具有异质性，通常表现为新生儿期发病的癫痫发作，对可用作吡哆醇（PN）或生物活性形式磷酸吡哆醛（PLP）的维生素B6治疗有反应。维生素B6依赖性癫痫由参与B6代谢的至少五个不同基因的突变引起。文献综述显示，全球仅报道了30例由突变引起的维生素B6依赖性癫痫患者。
我们报告了一例男婴病例，其父母为巴基斯坦近亲，男婴出生后数小时即出现全身性及局灶性癫痫发作，对PLP有反应。全外显子组测序显示一个纯合致病性变异NM_007198.4:c.46_47insCA，NP_009129.1:p.Leu17Hisfs，导致CA重复，从而使该基因发生移码。
由于缺陷导致的维生素B6依赖性癫痫是一种罕见疾病。即使早期治疗，发育结局也存在差异。据报道，很少有患者通过治疗达到最佳发育里程碑。PLP已被提倡作为缺陷的首选治疗方法，但口服PN在一些患者（包括我们的患者）中也显示出良好的癫痫控制效果。
对于具有提示磷酸吡哆胺5'-磷酸氧化酶（）缺陷生化特征的患者，由于缺陷导致的维生素B6依赖性癫痫是一个需要考虑的重要鉴别诊断，基因检测有助于做出正确诊断。及时诊断和治疗使大多数患者的癫痫得到了良好控制。
