{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:07:03Z","timestamp":1778688423496,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[1999,6,1]],"date-time":"1999-06-01T00:00:00Z","timestamp":928195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[1999,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The biochemical hallmark of glutaric aciduria type I (GA I) due to glutaryl\u2010CoA dehydrogenase deficiency is the accumulation of glutaric acid, and to a lesser degree of 3\u2010hydroxyglutaric and glutaconic acids. Abnormal metabolites vary from gross organic aciduria to only slightly or intermittently elevated or even normal excretion of glutaric acid, making the diagnosis sometimes difficult. Close to 100 pathogenic mutations have been identified in the gene encoding glutaryl\u2010CoA dehydrogenase. Specific mutations correlate with low or no excretion of glutaric acid, but there appears to be no correlation between genotype and clinical phenotype.<\/jats:p><jats:p>GA I causes unique age\u2010 and location\u2010specific neuropathological sequelae. Starting in the second half of gestation, maturation of the frontal and temporal cortex is hindered, leading to the characteristic appearance of frontotemporal atrophy. Between 6 and 18 months of age, relatively mild neurological symptoms may become exacerbated by fever or a catabolic state in the course of common infections or routine immunizations, by fasts required for surgery, or by minor head injuries. Putamen and caudate are destroyed, resulting in a permanent movement disorder that is similar to cerebral palsy and ranges from extreme hypotonia to choreoathetosis to rigidity with spasticity. Recently, the underlying pathophysiology could be delineated to an environmentally triggered age\u2010 and location\u2010specific overstimulation of the NMDA 2B receptor subtype.<\/jats:p><jats:p>Current therapy prevents brain degeneration in more than 90% of affected infants who are treated prospectively. Without treatment, more than 90% of affected children will develop severe neurological disabilities. Recognition of this disorder before the brain has been injured is essential to treatment. GA I may be recognized in routine neonatal screening performed with tandem mass spectrometry by an elevation of glutarylcarnitine. Where this is not done, timely diagnosis depends on the recognition of relatively nonspecific physical findings such as hypotonia, irritability, macrocephaly, on the detection of suggestive abnormalities in neuroimaging and on quantitative urinary organic acid analysis by gas chromatography \u2010 mass spectrometry.<\/jats:p>","DOI":"10.1023\/a:1005543904484","type":"journal-article","created":{"date-parts":[[2002,12,21]],"date-time":"2002-12-21T22:31:09Z","timestamp":1040509869000},"page":"381-391","source":"Crossref","is-referenced-by-count":98,"title":["Glutaric aciduria type I: From clinical, biochemical and molecular diversity to successful therapy"],"prefix":"10.1002","volume":"22","author":[{"given":"G. F.","family":"Hoffmann","sequence":"first","affiliation":[{"name":"Department of Neuropaediatrics and Metabolic Diseases Philipps University  Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Zschocke","sequence":"additional","affiliation":[{"name":"Department of Neuropaediatrics and Metabolic Diseases Philipps University  Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1999,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(89)80442-1"},{"issue":"1","key":"e_1_2_1_3_1","first-page":"34","article-title":"Sensitivity of free and total glutaric and 3\u2010OH\u2010glutaric acid measurements by stable isotopic dilution\u2010assays for the diagnosis of glutaric aciduric type I","volume":"20","author":"Baric I","year":"1997","journal-title":"J Inher Metab Dis"},{"key":"e_1_2_1_4_1","volume-title":"7th International Congress, 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