{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T04:44:23Z","timestamp":1768538663216,"version":"3.49.0"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T00:00:00Z","timestamp":1620432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Glutaric aciduria type II (GA-II) is a rare autosomal recessive disease caused by defects in electron transfer flavoprotein (ETF), ultimately causing insufficiencies in multiple acyl-CoA dehydrogenase (MAD). 3-phosphoglycerate dehydrogenase (3-PHGDH) deficiency, is another rare autosomal disorder that appears due to a defect in the synthesis of L-serine amino acid. Several mutations of ETFDH and PHGDH genes have been associated with different forms of GA-II and serine deficiency, respectively. In this study, we report a unique case of GA-II with serine deficiency using biochemical, genetic, and in silico approaches. The proband of Syrian descent had positive newborn screening (NBS) for GA-II. At two years of age, the patient presented with developmental regression, ataxia, and intractable seizures. Results of amino acid profiling demonstrated extremely low levels of serine. Confirmatory tests for GA-II and whole exome sequencing (WES) were performed to determine the etiology of intractable seizure. Sequencing results indicated a previously reported homozygous missense mutation, c.679 C&gt;A (p.Pro227Thr) in the ETFDH gene and a novel missense homozygous mutation c.1219 T&gt;C (p.Ser407Pro) in the PHGDH gene. In silico tools predicted these mutations as deleterious. Here, the clinical and biochemical investigations indicate that ETFDH:p.Pro227Thr and PHGDH:p.Ser407Pro variants likely underlie the pathogenesis of GA-II and serine deficiency, respectively. This study indicates that two rare autosomal recessive disorders should be considered in consanguineous families, more specifically in those with atypical presentation.<\/jats:p>","DOI":"10.3390\/genes12050703","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T21:32:46Z","timestamp":1620595966000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of ETFDH and PHGDH Mutations in a Patient with Mild Glutaric Aciduria Type II and Serine Deficiency"],"prefix":"10.3390","volume":"12","author":[{"given":"Amanat","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomics, United Arab Emirates University, Abu Dhabi P.O. Box 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahid Al","family":"Dhahouri","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, United Arab Emirates University, Abu Dhabi P.O. Box 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatmah Saeed Ali","family":"Almesmari","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, United Arab Emirates University, Abu Dhabi P.O. Box 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waseem Mahmoud","family":"Fathalla","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sheikh Shakhbout Medical City, Abu Dhabi P.O. Box 11001, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma Al","family":"Jasmi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, United Arab Emirates University, Abu Dhabi P.O. Box 15551, United Arab Emirates"},{"name":"Department of Pediatrics, Tawam Hospital, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jns.2014.08.040","article-title":"Amelioration of acylcarnitine profile using bezafibrate and riboflavin in a case of adult-onset glutaric acidemia type 2 with novel mutations of the electron transfer flavoprotein dehydrogenase (ETFDH) gene","volume":"346","author":"Shioya","year":"2014","journal-title":"J. Neurol. 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