Exploring the clinical, neuroimaging, and genetic spectrum of PLPBP deficiency: multicenter case series and systematic review

Alsini et al., 2026 | Mol Genet Metab | Systematic Review

Citation

Alsini Hanin, Al-Otaibi Ali, ... Alfadhel Majid. Exploring the clinical, neuroimaging, and genetic spectrum of PLPBP deficiency: multicenter case series and systematic review. Mol Genet Metab. 2026-Mar;147(3):109764. doi:10.1016/j.ymgme.2026.109764

Abstract

OBJECTIVE: To describe the phenotype, genotype, neuroimaging features, and outcome of PLPBP-related vitamin B6-dependent epilepsies. We present a systematic review, along with a multicenter case series of patients with PLPBP deficiency. METHODS: We collected individual data on clinical, radiological, genetic, and outcomes for a multicenter case series (n = 8) and all previously published cases (n = 46). We conducted a thematic analysis to identify consistent features across all cases and applied a clinical score system specifically developed to assess the impact of PLPBP-related vitamin B6-dependent epilepsy on neurodevelopmental and seizure outcome in each case. RESULTS: We identified 14 eligible studies involving 46 patients. Including our additional cases, the total number of individuals with PLPBP variants increased to 54. The most common type of variant was missense variants (48%), with the variant c.370-373del being the most frequently reported (18.5%). Based on our clinical severity scoring system, which evaluates the degree of neurodevelopmental impairment and seizure control, more than two thirds of patients were classified as having moderate to severe disease. All individuals in the reviewed studies presented with early neonatal seizures, with the majority occurring within the first 24 h of life (55.5%) or the first week of life (76%). Common clinical features observed included antenatal anomalies, prematurity, fetal distress, and microcephaly. Analysis of brain MRI studies identified anomalies in 65% of cases, including white matter abnormalities (54%), periventricular or temporal cysts (27%), anomalies of the corpus callosum (15.4%), and global brain underdevelopment with broad gyri and shallow sulci (44%). Genotype-phenotype analysis revealed an association of missense variants and compound heterozygous variants with an attenuated phenotype, while biallelic truncating variants and homozygous variants were linked to severe phenotypes and/or early mortality. CONCLUSIONS: This systematic review and multicenter case series of a large cohort of individuals with PLPBP deficiency delineates the clinical, radiological, and genetic spectrum of PLPBP-related vitamin B6-related epilepsies, an autosomal-recessive disease. It also highlights the best treatment approaches and potential predictors for disease severity and survival.

Key Findings

We identified 14 eligible studies involving 46 patients. Including our additional cases, the total number of individuals with PLPBP variants increased to 54. The most common type of variant was missense variants (48%), with the variant c.370-373del being the most frequently reported (18.5%). Based on our clinical severity scoring system, which evaluates the degree of neurodevelopmental impairment and seizure control, more than two thirds of patients were classified as having moderate to severe d

Outcomes Measured

• Requires manual extraction

Population

MeSH Terms

• Humans
• Neuroimaging
• Female
• Male
• Epilepsy
• Phenotype
• Infant
• Child, Preschool
• Child
• Carrier Proteins
• Infant, Newborn
• Seizures
• Genotype
• Magnetic Resonance Imaging

Evidence Classification

• Level: Systematic Review
• Publication Types: Journal Article, Systematic Review
• Vertical: vitamin-b6

Provenance

• PMID: 41671913
• DOI: 10.1016/j.ymgme.2026.109764
• PMCID: Not in PMC
• Verified: 2026-04-09 via PubMed E-utilities API

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