Clinical and genetic characteristics of pyridoxine-dependent epilepsy / 西安交通大学学报(医学版)

【Objective】 To analyze the clinical features and gene mutation characteristics of four children with pyridoxine-dependent epilepsy (PDE) in order to provide evidence for early diagnosis of this rare disease. 【Methods】 The clinical data of four cases of PDE were collected from January 2016 to June 2019 in The Second Affiliated Hospital of Xi’an Jiaotong University. We collected data of the laboratory examination, electroencephalogram, and magnetic resonance imaging (MRI). Peripheral venous blood was collected from children and parents, genomic DNA was extracted from white blood cells, and primers were designed to amplify the aldehyde dehydrogenase 7 family member A1(ALDH7A1) on the long arm of chromosome 5 using PCR; exon and the junction of exon and intron were also amplified to determine whether there is a gene mutation. 【Results】 All the 4 cases had a full-term birth and no history of birth asphyxia. ① Clinical features: onset time from 8 days after birth to 6 months after birth. Type of seizure: 1 case with myoclonus onset, then converted to spasm; 1 case for generalized seizures; 2 cases for partial seizures, then converted to generalized seizures; 3 cases were prone to epileptic seizures; 1 case was significantly worse after infection; MRI: 3 cases showed no abnormalities, 1 case showed non-specific abnormalities; EEG: One case was fragmentary hypsarrhythmia, 3 cases of multifocal epileptiform discharge; Treatment: a small dose of vitamin B6 could control the seizure, 1 of them was controlled at a tiny dose, and 3 cases were controlled by a small dose. ② Genetic analysis results: There were 4 cases of ALDH7A1 gene mutation, of which 3 cases were known gene mutations and 1 case was new mutation. 【Conclusion】 PDE has an early onset, often in the neonatal or small infancy, is prone to epilepticus and has an increased severity after infection. There is no specificity in seizure type, EEG or MRI. The analysis of ALDH7A1 gene and vitamin B6 load test can help to confirm the diagnosis, small dose of Vitamin B6 can control the seizures so as to provide reference for the dose of vitamin B6. However, the number of cases is small, and a large sample size is still needed for verification.

Vitamin B6 related epilepsy / 中华实用儿科临床杂志

Vitamin B6 related epilepsy is a group of epileptic diseases,seizures in which could not be con-trolled by antiepileptic drugs,but could be controlled or obviously improved by vitamin B6 .It comprises of pyridoxine dependent epilepsy and pyridoxine responsive epilepsy predominantly,and the latter includes vitamin B6 responsive in-fantile spasms,pyridox(am)ine -5′-phosphate oxidase (PNPO)deficiency,hyperphosphatasia mental retardation syndrome (Mabry syndrome)and so on.The clinical presentations of the diseases above are nonspecific,manifesting as refractory seizures onset in neonatal or infantile period,which need to be distinguished from other diseases such as new-born hypoxic ischemic encephalopathy,Ohtahara syndrome and non -ketotic hyperglycinemia.Pyridoxine dependent epilepsy,PNPO deficiency and Mabry syndrome have relative specific biomarkers and known disease -causing genes, which are helpful for diagnosis.It is suggested that pyridoxine or pyridoxal phosphate should be tried first for all patients started seizures early (including all infantile spasms patients),avoiding missing these diseases.And once diagnosed,vi-tamin B6 should be maintained long -term or all the life according to the detailed disease.

Clinical analysis of pyridoxine-dependent epilepsy in a child and ALDH7A1 mutation / 中华实用儿科临床杂志

Objective To analyze clinical diagnosis and treatment,aldehyde dehydrogenase 7 family member A1 (ALDH7A1) gene mutations in 1 Chinese child with pyridoxine dependent epilepsy(PDE).Methods The clinical manifestations and course of treatment were observed in a PDE patient with early epilepsy onset.Video-electroencephalogram(VEEG) and magnetic resonance imaging (MRI) were performed.The mutations of ALDH7A1 gene were examined.Results At the age of 2 months,recurrent epileptic seizures occurred and the child was resistant to antiepileptic drugs.Patient hospitalized several times due to frequent seizures and pyridoxine was used intravenously for several days.For each hospital stay,the frequent seizures were controlled completely under the treatment of pyridoxine and antiepileptic drugs.Seizures recurred at intervals of 13,14 and 38 days due to the treatment with antiepileptic drugs only without pyridoxine.Continuing oral pyridoxine without anticonvulsants led to seizure free for 5 months.No epileptiform discharges were found during several interictal VEEG monitoring and MRI showed normal.ALDH7A1 gene mutation analysis revealed two heterozygote mutations:c.410G ＞ A (p.G137E) in exon 5 that was transmitted from the father,and IVS11 + 1G ＞ A in intron 11 transmitted from the mother.Conclusions Early onset seizures have better response to pyridoxine and recurred after pyridoxine withdrawal in the patient,which suggested that he is a PDE patient.The interictal normal EEG could not rule out the possibility of PDE.This is the first report on ALDH7A1 mutations in PDE patient in China.Both the c.410G ＞ A(p.G137E) and IVS11 + 1G ＞ A mutations have not been reported previously.