Mohanlal Smilu, Bindu Parayil Sankaran, Sureshbabu Sachin, Kumar Suresh
Department of Neurology and Paediatric Neurosciences, Aster Malabar Institute of Medical Sciences, Kozhikode, Kerala, India.
Mito-Foundation Clinical Fellow, Genetic metabolic disorders service children's hospital, Westmead, NSW, Australia.
Epilepsy Behav Rep. 2020 Mar 24;14:100357. doi: 10.1016/j.ebr.2020.100357. eCollection 2020.
A 6-year-old girl presented with history of infantile onset epileptic encephalopathy and developmental delay. She had polymorphic seizures that were refractory to regular anti-seizure medication. Incomplete control of seizures was achieved on starting pyridoxine, riboflavin and thiamine. Clinical exome sequencing done at 4 years revealed PNPO deficiency with a homozygous mutation in the highly conserved exon 3:c.352G > A p.Gly118R region of the gene. Thereafter, pyridoxine was weaned and pyridoxal phosphate was added with resultant refractory status epilepticus, which necessitated our approach to start pyridoxine and stop pyridoxal phosphate. With two antiseizure medication and three vitamins, she had improved seizure control. At 6 years of age an attempt to wean off riboflavin resulted in break through seizures. After restarting riboflavin along with pyridoxal phosphate, pyridoxine in low doses and two antiseizure medications, the child achieved good seizure control. Though partial responsiveness to pyridoxine with gene mutation in the exon 3: c.352G > A p. Gly118R is known, riboflavin dependence and transient worsening of seizures off pyridoxine has not been described to our knowledge. Our case highlights the importance of identifying the precise gene mutationsequence to properly identify variants relative to individual phenotypic expression, treatment responsivness and need for added vitamin supplementation.
一名6岁女孩有婴儿期起病的癫痫性脑病和发育迟缓病史。她有多种类型的癫痫发作，对常规抗癫痫药物难治。开始使用吡哆醇、核黄素和硫胺素后癫痫发作得到部分控制。4岁时进行的临床外显子组测序显示PNPO缺乏，该基因高度保守的外显子3：c.352G＞A p.Gly118R区域存在纯合突变。此后，停用吡哆醇并添加磷酸吡哆醛，结果导致难治性癫痫持续状态，这使得我们采取重新开始使用吡哆醇并停用磷酸吡哆醛的方法。使用两种抗癫痫药物和三种维生素后，她的癫痫发作控制情况有所改善。6岁时尝试停用核黄素导致癫痫发作突破。重新开始使用核黄素以及磷酸吡哆醛、低剂量吡哆醇和两种抗癫痫药物后，患儿癫痫发作得到良好控制。虽然已知外显子3：c.352G＞A p.Gly118R基因突变对吡哆醇有部分反应，但据我们所知，尚未描述核黄素依赖性和停用吡哆醇后癫痫发作的短暂恶化情况。我们的病例强调了识别精确基因突变序列对于相对于个体表型表达、治疗反应性和额外维生素补充需求来正确识别变异体的重要性。
