{"doi":"10.1111/cge.14479","title":"Further delineation of the phenotypic and metabolomic profile of <i>ALDH1L2</i>‐related neurodevelopmental disorder","abstract":"Abstract ALDH1L2, a mitochondrial enzyme in folate metabolism, converts 10‐formyl‐THF (10‐formyltetrahydrofolate) to THF (tetrahydrofolate) and CO 2 . 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 abnormalities in these fibroblasts include reduced NADPH/NADP + ratio and pool of mitochondrial ATP, upregulated autophagy and dramatically altered metabolomic profile. Overall, our study further supports a link between ALDH1L2 deficiency and abnormal neurodevelopment in humans.","journal":"Clinical Genetics","year":2024,"id":476192,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302578,"name":"Hanan E. Shamseldin","orcid":"0000-0002-6199-3523","position":1,"is_corresponding":false},{"id":714096,"name":"Halle M. Fogle","orcid":"0000-0001-6334-4407","position":2,"is_corresponding":false},{"id":430167,"name":"Blake R. Rushing","orcid":"0000-0002-8662-3270","position":3,"is_corresponding":false},{"id":1313450,"name":"Reem H. AlMalki","orcid":"0000-0001-5221-5634","position":4,"is_corresponding":false},{"id":1313814,"name":"Amal Jaafar","orcid":null,"position":5,"is_corresponding":false},{"id":352352,"name":"Mais Hashem","orcid":null,"position":6,"is_corresponding":false},{"id":510689,"name":"Firdous Abdulwahab","orcid":null,"position":7,"is_corresponding":false},{"id":458595,"name":"Anas M. Abdel Rahman","orcid":"0000-0002-9527-9424","position":8,"is_corresponding":false},{"id":467071,"name":"Natalia I. Krupenko","orcid":"0000-0003-2977-1557","position":9,"is_corresponding":false},{"id":291081,"name":"Fowzan S. Alkuraya","orcid":"0000-0003-4158-341X","position":10,"is_corresponding":false},{"id":402560,"name":"Sergey A. Krupenko","orcid":"0000-0002-6926-2776","position":11,"is_corresponding":false},{"id":482590,"name":"Mikyoung You","orcid":"0000-0002-0908-113X","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:06:25.428435Z","pmid":"38193334","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}