{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:47:04Z","timestamp":1768427224532,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T00:00:00Z","timestamp":1699747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>MT\u2010TL2<\/jats:italic> m.12315G&gt;A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5\u2010year\u2010old child with heteroplasmy for this variant who developed neurological regression and stroke\u2010like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke\u2010like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low <jats:italic>z<\/jats:italic>\u2010scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke\u2010like episodes. The use of intravenous arginine during stroke\u2010like episodes and daily enteral L\u2010citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1\u2010methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N\u2010acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant <jats:italic>MT\u2010TL2<\/jats:italic> m.12315G&gt;A to include neurological regression and a MELAS\u2010like phenotype. Individuals with this variant should undergo in\u2010depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment.<\/jats:p>","DOI":"10.1002\/ajmg.a.63461","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:20:00Z","timestamp":1699842000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Heteroplasmic pathogenic m.<scp>12315G<\/scp>&gt;A variant in <scp><i>MT\u2010TL2<\/i><\/scp> presenting with <scp>MELAS<\/scp> syndrome and depletion of nitric oxide donors"],"prefix":"10.1002","volume":"194","author":[{"given":"Matthew T.","family":"Snyder","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas 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