Evidence map›Paper›PMID 40533849›Full record

SynthesisOrphanet journal of rare diseases2025

The difference of variation types between late-onset multiple acyl-CoA dehydrogenase deficiency patients carrying biallelic and single heterozygous variations in ETFDH: a systematic review and meta-analysis.

Huiqiu Zhang, Jing Ma, Menghan Su, Junsen Zhao, Weisong Duan, Juan Wang, Dan Liu, Junhong Guo, Xueli Chang, Wei Zhang and 1 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

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5citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. HPlant cell reports · 2026
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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Huiqiu Zhang *Department of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Jing Ma *Department of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Menghan SuDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Junsen ZhaoDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Weisong DuanDepartment of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
Juan WangDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Dan LiuDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Junhong GuoDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Xueli ChangDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China.
Wei ZhangDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China. zhangvey@126.com.
Rongjuan ZhaoDepartment of Neurology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Street, Taiyuan, 030012, China. zhaorongjuan@sxmu.edu.cn.ORCID http://orcid.org/0000-0001-6533-9126

Funding

National Natural Science Foundation 82471432Shanxi Science and Technology Department 202203021212037
6 · The paper itself

Abstract

backgroundLate-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disease chiefly caused by mutations in ETFDH gene. Mutations in the ETFDH gene lead to abnormal structure, impaired function, and increased degradation of ETFDH protein. However, it is not known why approximately 10% of patients carry single heterozygous variants in ETFDH. We speculate that different variation types (e.g., null variants and missense variants) partially account for the phenomenon.

methodsIn this study, six databases were searched up until December 01, 2024. Studies describing late-onset MADD patients carrying ETFDH variations were included. The analyses focused on the differences in variation types, computational pathogenicity scores of missense variants, and clinical characteristics between patients with biallelic and single heterozygous variations (biallelic group vs heterozygous group).

resultsOf the initially screened 3638 studies, 30 met the inclusion criteria, including 498 late-onset MADD patients with biallelic variations and 62 with single heterozygous variations in ETFDH. The relative frequency of patients carrying null variants was lower in the biallelic group (21%, 95% CI [16%-27%]) than that in the heterozygous group (34%, 95% CI [23%-48%]) (P = 0.044). Missense variants in the heterozygous group had stronger pathogenicity than those in the biallelic group, as reflected by the computational prediction tools, SIFT, PolyPhen-2 and metaRNN (P < 0.05). Patients carrying biallelic variations had a younger onset age and a higher level of serum creatine kinase at diagnosis (P < 0.05).

conclusionsLate-onset MADD patients carrying single heterozygous variations in ETFDH gene have distinct variation profiles and clinical severity compared to those harboring biallelic variations, which highlights the complexity of this disease.

Indexed as

Electron-Transferring FlavoproteinsIron-Sulfur ProteinsMultiple Acyl Coenzyme A Dehydrogenase DeficiencyOxidoreductases Acting on CH-NH Group DonorsAge of OnsetAllelesHeterozygoteHumansMutationMutation, Missenseelectron-transferring-flavoprotein dehydrogenaseElectron-Transferring FlavoproteinsIron-Sulfur ProteinsOxidoreductases Acting on CH-NH Group DonorsETFDHLate-onset multiple acyl-CoA dehydrogenase deficiencyMeta-analysisSingle heterozygous variationsVariation types

Identifiers

PMID40533849
PMCPMC12178022

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.