Case Report: A novel hemizygous missense PDHA1 variant in a Vietnamese boy with pyruvate dehydrogenase E1-alpha deficiency.
| Title: | Case Report: A novel hemizygous missense PDHA1 variant in a Vietnamese boy with pyruvate dehydrogenase E1-alpha deficiency. |
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| Authors: | Nguyen TTN; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Khanh NN; Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children's Hospital, Hanoi, Vietnam.; Vu CD; Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children's Hospital, Hanoi, Vietnam.; Nguyen NL; Center for Gene and Protein Research, Hanoi Medical University, Hanoi, Vietnam.; Tran VK; Center for Gene and Protein Research, Hanoi Medical University, Hanoi, Vietnam.; Lien NTK; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Van Tung N; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Quan ND; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Hien NT; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Giang TTH; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Xuan NT; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Tao NT; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.; Khoa TV; Department of Biology and Medical Genetics, Vietnam Military Medical University, Hanoi, Vietnam.; Nguyen HH; Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam. |
| Source: | Frontiers in pediatrics [Front Pediatr] 2024 Dec 10; Vol. 12, pp. 1494604. Date of Electronic Publication: 2024 Dec 10 (Print Publication: 2024). |
| Publication Type: | Case Reports; Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101615492 Publication Model: eCollection Cited Medium: Print ISSN: 2296-2360 (Print) Linking ISSN: 22962360 NLM ISO Abbreviation: Front Pediatr Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Lausanne : Frontiers Media SA, [2013]- |
| Abstract: | A pyruvate dehydrogenase complex deficiency causes a reduction in adenosine triphosphate production and energy insufficiency, leading to neurological disorders. An abnormal E1-alpha protein originating from the PDHA1 gene with pathogenic variants is unable to communicate with E1-beta for the formation of the E1 enzyme, decreasing pyruvate dehydrogenase complex activity. In this study, we report a Vietnamese boy with lethargy, severe metabolic acidosis, increased serum lactate, hyperalaninemia, lactic acidosis, and globus pallidus lesions. Whole-exome sequencing and variant filtering identified a hemizygous missense variant NM000284.4 (PDHA1): c.479T>G (p.Phe160Cys) in the patient. The variant c.479T>G caused a single nucleotide substitution on exon 5 and was predicted to be a disease-causing variant in the in silico analyses. We present the first report with a genetic analysis of a Vietnamese patient with pyruvate dehydrogenase E1-alpha deficiency (PDHAD). Sanger sequencing demonstrated that the patient inherited the variant from his mother who harbored the variant in a heterozygous state, but no PDHAD symptoms were observed in her. In addition, a prenatal test of the patient's mother revealed a fetus with a normal genotype. Furthermore, the patient's father and sister both carried a normal allele. Based on the American College of Medical Genetics criteria, the variant c.479T>G was predicted to be a likely pathogenic variant. Using the combination of the patient's genotype and phenotype, he was definitively diagnosed with pyruvate dehydrogenase E1-alpha deficiency. Our findings expand the mutational spectrum of neurological disorders and provide the scientific basis for genetic counseling for the patient's family.; (© 2024 Nguyen, Khanh, Vu, Nguyen, Tran, Lien, Van Tung, Quan, Hien, Giang, Xuan, Tao, Khoa and Nguyen.) |
| Competing Interests: | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: PDHA1; Vietnamese; missense variant; pyruvate dehydrogenase E1-alpha deficiency; whole-exome sequencing |
| Entry Date(s): | Date Created: 20241225 Latest Revision: 20250104 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11666387 |
| DOI: | 10.3389/fped.2024.1494604 |
| PMID: | 39720099 |
| Database: | MEDLINE |
Case Reports; Journal Article