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Novel IBA57 mutations in two chinese patients and literature review of multiple mitochondrial dysfunction syndrome

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Abstract

Multiple mitochondrial dysfunction syndrome (MMDS) refers to a class of mitochondrial diseases caused by nuclear gene mutations, which usually begins in early infancy and is classically characterized by markedly impaired neurological development, generalized muscle weakness, lactic acidosis, and hyperglycinemia, cavitating leukoencephalopathy, respiratory failure, as well as early fatality resulted from dysfunction of energy metabolism in multiple systems. So far, six types of MMDS have been identified based on different genotypes, which are caused by mutations in NFU1, BOLA3, IBA57, ISCA2, ISCA1 and PMPCB, respectively. IBA57 encodes a protein involved in the mitochondrial Fe/S cluster assembly process, which plays a vital role in the activity of multiple mitochondrial enzymes. Herein, detailed clinical investigation of 2 Chinese patients from two unrelated families were described, both of them showed mildly delay in developmental milestone before disease onset, the initial symptoms were all presented with acute motor and mental retrogression, and brain MRI showed diffused leukoencephalopathy with cavities, dysplasia of corpus callosum and cerebral atrophy. Exome sequencing revealed three IBA57 variants, one shared variant (c.286T>C) has been previously reported, the remaining two (c.189delC and c.580 A>G) are novel. To enhance the understanding of this rare disease, we further made a literature review about the current progress in clinical, genetic and treatment of the disorder. Due to the rapid progress of MMDS, early awareness is crucial to prompt and proper administration, as well as genetic counseling.

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The raw data are available upon reasonable request.

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Acknowledgements

We would like to thank the guardians of the patients for the support and cooperation.

Author information

Author notes

  1. Feixia Zhan and Xiaoli Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yi Shan Road, Shanghai, 200233, China

    Feixia Zhan, Ruilong Ni, Taotao Liu, Yuwen Cao, Jingying Wu, Wotu Tian, Xinghua Luan & Li Cao

  2. Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, 201406, China

    Xiaoli Liu

  3. School of Medicine, Anhui University of Science and Technology, 232001, Huainan, China

    Ruilong Ni & Taotao Liu

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  1. Feixia Zhan
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Contributions

Feixia Zhan: Data acquisition, analysis and interpretation of data, and drafted the manuscript for intellectual content. This work was supported by the grants from the National Natural Science Foundation of China (No.81,870,889 and 82,071,258) and Shanghai Municipal Commission of Health and Family Planning (20184Y0056).

Xiaoli Liu: Funding, data acquisition, interpreted the data, and revised the manuscript for intellectual content.

Ruilong Ni: Data acquisition.

Taotao Liu: Data acquisition.

Yuwen Cao: Data acquisition.

Jingying Wu: Data acquisition.

Wotu Tian: Data acquisition.

Xinghua Luan: Data acquisition, analysis and interpretation of data, and revised the manuscript for intellectual content.

Li Cao: Funding, study design and conceptualization, analysis and interpretation of data, manuscript revision, and supervision.

Corresponding authors

Correspondence to Xinghua Luan or Li Cao.

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Ethics approval

The study was approved by the ethics committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China. Written informed consent, which also included the consent for the publication of medical information, was obtained from the guardians.

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All authors in this study have no conflict of interest.

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Zhan, F., Liu, X., Ni, R. et al. Novel IBA57 mutations in two chinese patients and literature review of multiple mitochondrial dysfunction syndrome. Metab Brain Dis 37, 311–317 (2022). https://doi.org/10.1007/s11011-021-00856-8

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  • DOI: https://doi.org/10.1007/s11011-021-00856-8

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