{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:35:04Z","timestamp":1790501704042,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"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":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methionine synthase deficiency (<jats:italic>cblG<\/jats:italic> complementation group) is a rare inborn error of metabolism affecting the homocysteine re\u2010methylation pathway. It leads to a biochemical phenotype of hyperhomocysteinemia and hypomethioninemia. The clinical presentation of <jats:italic>cblG<\/jats:italic> is variable, ranging from seizures, encephalopathy, macrocytic anemia, hypotonia, and feeding difficulties in the neonatal period to onset of psychiatric symptoms or acute neurologic changes in adolescence or adulthood. Given the variable and nonspecific symptoms seen in <jats:italic>cblG<\/jats:italic>, the diagnosis of affected patients is often delayed. Medical management of <jats:italic>cblG<\/jats:italic> includes the use of hydroxocobalamin, betaine, folinic acid, and in some cases methionine supplementation. Treatment has been shown to lead to improvement in the biochemical profile of affected patients, with lowering of total homocysteine levels and increasing methionine levels. However, the published literature contains differing conclusions on whether treatment is effective in changing the natural history of the disease. Herein, we present five patients with <jats:italic>cblG<\/jats:italic> who have shown substantial clinical benefit from treatment with objective improvement in their neurologic outcomes. We demonstrate more favorable outcomes in our patients who were treated early in life, especially those who were treated before neurologic symptoms manifested. Given improved outcomes from treatment of presymptomatic patients, <jats:italic>cblG<\/jats:italic> warrants inclusion in newborn screening.<\/jats:p>","DOI":"10.1002\/jimd.12448","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T12:42:07Z","timestamp":1633783327000},"page":"157-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Methionine synthase deficiency: Variable clinical presentation and benefit of early diagnosis and treatment"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-9974","authenticated-orcid":false,"given":"Kimberly A.","family":"Kripps","sequence":"first","affiliation":[{"name":"Section of Genetics and Metabolism University of Colorado Anschutz Medical Campus  Aurora Colorado USA"},{"name":"Department of Molecular and Medical Genetics Oregon Health &amp; Science University  Portland Oregon 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