Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review

source extracted confidence: high 2026-04-09
#humans #infant-newborn #aldehyde-dehydrogenase #epilepsy #genotype

Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review

Fang et al., 2024 | Epilepsy Res | Systematic Review

Citation

Fang Chuchu, Yang Lin, ... Zhou Wenhao. Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review. Epilepsy Res. 2024-May;202:107363. doi:10.1016/j.eplepsyres.2024.107363

Abstract

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a rare autosomal recessive disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase. This study aimed to systematically explore genotypic and phenotypic features and prognostic factors of neonatal-onset PDE. A literature search covering PubMed, Elsevier, and Web of Science was conducted from January 2006 to August 2023. We identified 56 eligible studies involving 169 patients and 334 alleles. The c.1279 G>C variant was the most common variant of neonatal-onset PDE (25.7 %). All patients were treated with pyridoxine; forty patients received dietary intervention therapy. 63.9 % of the patients were completely seizure-free; however, 68.6 % of the patients had neurodevelopmental delays. Additionally, homozygous c.1279 G>C variants were significantly associated with ventriculomegaly, abnormal white matter signal, and cysts (P<0.05). In contrast, homozygous c.1364 T>C was associated with clonic seizure (P=0.031). Pyridoxine used immediately at seizure onset was an independent protective factor for developmental delay (P=0.035; odds ratio [OR]: 3.14). Besides, pyridoxine used early in the neonatal period was a protective factor for language delay (P=0.044; OR: 4.59). In contrast, neonatal respiratory distress (P=0.001; OR: 127.44) and abnormal brain magnetic resonance imaging (P=0.049; OR: 3.64) were risk factors. Prenatal movement abnormality (P=0.041; OR: 20.56) and abnormal white matter signal (P=0.012; OR: 24.30) were risk factors for motor delay. Myoclonic seizure (P=0.023; OR: 7.13) and status epilepticus (P=0.000; OR: 9.93) were risk factors for breakthrough seizures. In conclusion, our study indicated that pyridoxine should be started immediately when unexplained neonatal seizures occur and not later than the neonatal period to prevent poor neurodevelopmental outcomes.

Key Findings

In conclusion, our study indicated that pyridoxine should be started immediately when unexplained neonatal seizures occur and not later than the neonatal period to prevent poor neurodevelopmental outcomes.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 169
Age Range See abstract
Condition stress

MeSH Terms

  • Humans
  • Infant, Newborn
  • Aldehyde Dehydrogenase
  • Epilepsy
  • Genotype
  • Phenotype
  • Prognosis
  • Pyridoxine
  • Seizures

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Research Support, Non-U.S. Gov't, Systematic Review
  • Vertical: vitamin-b6

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09