[Phenotype of infantile epileptic spasm syndrome in pyridoxin-dependent epilepsy]

To analyze the clinical diagnosis, treatment, and prognosis of the patients with pyridoxine-dependent epilepsy (PDE) characterized by infantile epileptic spasm syndrome (IESS).

A total of 75 PDE patients with ALDH7A1 variants were diagnosed at the Department of Pediatrics of Peking University First Hospital and Peking University People's Hospital from July 2012 to June 2024, and five PDE patients with the phenotype of IESS were selected. The clinical manifestations, treatment, blood biochemistry, metabolic screening, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), and gene testing results of the five PDE patients were analyzed.

Among the five patients diagnosed with PDE, three were female and two were male, and the phenotype was consistent with IESS. The age at the last follow-up was from one year and 3 months to 11 years and 9 months. All the five cases were delivered at term. Two cases had anoxia and asphyxia at birth, and three cases had normal birth history. The onset age of seizure ranged from one day to 4 months after birth. One case presented with epileptic spasms (ES), and three cases presented with focal seizure and ES. The other patient was started with ES, followed by multiple seizure types, including focal seizure and generalized tonic-clonic seizure, and developed epileptic status which caused secondary brain injury. The interictal EEG results showed hypsarrhythmia in three cases, generalized and multifocal discharges in one cases, and multifocal discharges in one case. No abnormalities were found in brain MRI in three cases, and secondary cerebral atrophy and hydrocephalus were observed in two cases during the course of the disease. Gene analysis confirmed that the five patients carried compound heterozygous variants of ALDH7A1, and two of them carried exon deletion variants. High dose pyridoxine treatment started at the end of 2 days, 4 years, 3 years, 4 days. and 2 months after the onset of the disease. Up to the last follow-up, seizures of four cases were controlled, followed by normal EEG. One patient with brain atrophy had uncontrolled seizures and EEG remained abnormal. The neurodevelopment of the three patients were severely delayed, and two were mildly delayed.

IESS could be a rare phenotype of PDE. High doses of pyridoxine can control or reduce the frequency of seizures. Delayed diagnosis and treatment, secondary brain injury, and the genotype, especially deletions variants, were associated with poor prognosis.