{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:37:15Z","timestamp":1785753435124,"version":"3.56.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>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 <jats:italic>PDHA1<\/jats:italic> 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 (<jats:italic>PDHA1<\/jats:italic>): c.479T&amp;gt;G (p.Phe160Cys) in the patient. The variant c.479T&amp;gt;G caused a single nucleotide substitution on exon 5 and was predicted to be a disease-causing variant in the <jats:italic>in silico<\/jats:italic> 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&amp;gt;G was predicted to be a likely pathogenic variant. Using the combination of the patient\u2019s 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.<\/jats:p>","DOI":"10.3389\/fped.2024.1494604","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T04:26:02Z","timestamp":1733804762000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: A novel hemizygous missense PDHA1 variant in a Vietnamese boy with pyruvate dehydrogenase E1-alpha deficiency"],"prefix":"10.3389","volume":"12","author":[{"given":"Thi Thanh Ngan","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Ngoc","family":"Khanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi 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