Further delineation of the phenotypic and metabolomic profile of ALDH1L2-related neurodevelopmental disorder.

ABSTRACT: ALDH1L2, a mitochondrial enzyme in folate metabolism, converts 10-formyl-THF (10-formyltetrahydrofolate) to THF (tetrahydrofolate) and CO₂. At the cellular level, deficiency of this NADP⁺-dependent reaction results in marked reduction in NADPH/NADP⁺ ratio and reduced mitochondrial ATP. Thus far, a single patient with biallelic ALDH1L2 variants and the phenotype of a neurodevelopmental disorder has been reported. Here, we describe another patient with a neurodevelopmental disorder associated with a novel homozygous missense variant in ALDH1L2, Pro133His. The variant caused marked reduction in the ALDH1L2 enzyme activity in skin fibroblasts derived from the patient as probed by 10-FDDF, a stable synthetic analog of 10-formyl-THF. Additional associated abnorma

SUBMITTER: You M 

PROVIDER: S-EPMC10990829 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature