{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:30:35Z","timestamp":1783704635457,"version":"3.55.0"},"reference-count":28,"publisher":"Necmettin Erbakan University Press","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pediatr Genet"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glutaric acidemia type 1 (GA-1, OMIM 231670) is an autosomal recessive inborn error of metabolism caused by the deficiency of glutaryl-coenzyme A (CoA) dehydrogenase with most children presenting in infancy with encephalopathy, dystonia, and macrocephaly. In this article, we presented the clinical characteristics, molecular profile, and outcomes in 29 unrelated families with affected children (30 cases total). The mean age at onset of illness was 10 months (\u00b114.58), whereas the mean age at referral for molecular diagnosis was 29.44 months (\u00b128.11). Patients were residents of nine different states of India. Clinical presentation varied from acute encephalitis followed by neuroregression and chronic\/insidious developmental delay. Neurological sequelae varied from asymptomatic (no sequelae, 2 patients) to moderate (5 patients) and severe (23 patients) sequelae. All patients underwent blood tandem mass spectrometry (TMS on dried blood spots) and\/or urine gas chromatography mass spectrometry (GCMS). Neuroimaging demonstrated batwing appearance in 95% cases. Sanger's sequencing of GCDH, covering all exons and exon\u2013intron boundaries, was performed for all patients. Variants identified include 15 novel coding variants: p.Met100Thr, p.Gly107Ser, p.Leu179Val, p.Pro217Ser, p. Phe236Leufs*107, p.Ser255Pro, p.Met266Leufs*2, p.Gln330Ter, p.Thr344Ile, p.Leu345Pro, p.Lys377Arg, p.Leu424Pro, p.Asn373Lys, p.Lys377Arg, p.Asn392Metfs*9, and nine known genetic variants such as p.Arg128Gln, p.Leu179Arg, p.Trp225Ter, p.Met339Val, p.Gly354Ser, p.Arg402Gln, p.Arg402Trp, p.His403Tyr, and p.Ala433Val (Ensembl transcript ID: ENST00000222214). Using in silico analysis, genetic variants were shown to be affecting the residues responsible for homotetramer formation of the glutaryl-CoA dehydrogenase protein. Treatment included oral carnitine, riboflavin, protein-restricted diet, lysine-deficient special formulae, and management of acute crises with intravenous glucose and hydration. However, the mortality (9\/30, 27.58%) and morbidity was high in our cohort with only two patients affording the diet. Our study is the largest multicentric, genetic variant\u2013proven series of glutaric aciduria type 1 from India till date.<\/jats:p>","DOI":"10.1055\/s-0040-1715528","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T19:09:42Z","timestamp":1599073782000},"page":"213-221","source":"Crossref","is-referenced-by-count":12,"title":["Clinical Characteristics, Molecular Profile, and Outcomes in Indian Patients with Glutaric Aciduria Type 1"],"prefix":"10.53391","volume":"10","author":[{"given":"Parag M.","family":"Tamhankar","sequence":"additional","affiliation":[{"name":"Genetic Research Center, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India"},{"name":"Centre for Medical Genetics, Mumbai, Maharashtra, India"},{"name":"Sandor Life Sciences Pvt. Ltd., Hyderabad, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Genetic Research Center, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratima","family":"Kondurkar","sequence":"additional","affiliation":[{"name":"Genetic Research Center, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0136-3108","authenticated-orcid":false,"given":"Sarfaraj","family":"Niazi","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Center of Indian Council of Medical Research, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Christopher","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaval","family":"Solanki","sequence":"additional","affiliation":[{"name":"Mantra Child and Neurology and Epilepsy Clinic, Bhavnagar, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Dholakia","sequence":"additional","affiliation":[{"name":"Government Medical College, Bhavnagar, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-827X","authenticated-orcid":false,"given":"Mamta","family":"Muranjan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seth Gordhandas Sunderdas Medical College and King Edward Memorial hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Kamate","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Jawaharlal Nehru Medical College, Karnataka Lingayat Education University, Belgaum, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Kalane","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Centre, Swargate, Pune, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5936-5192","authenticated-orcid":false,"given":"Jayesh","family":"Sheth","sequence":"additional","affiliation":[{"name":"Foundation for Research in Genetics and Endocrinology Institute of Human Genetics, Foundation for Research in Genetics and Endocrinology House, Satellite, Ahmedabad, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasundhara","family":"Tamhankar","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Gulati","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Gorimedu, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9336-6831","authenticated-orcid":false,"given":"Madhavi","family":"Vasikarla","sequence":"additional","affiliation":[{"name":"Fernandez Hospital, Hyderabad, Telengana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-370X","authenticated-orcid":false,"given":"Sumita","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaik M.","family":"Naushad","sequence":"additional","affiliation":[{"name":"Sandor Life Sciences Pvt. 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An e-Science approach with life scientist friendly interfaces","volume":"11","author":"H Venselaar","year":"2010","journal-title":"BMC Bioinformatics"},{"issue":"08","key":"ref14","first-page":"869","article-title":"Trivandrum developmental screening chart","volume":"28","author":"M KC Nair","year":"1991","journal-title":"Indian Pediatr"},{"key":"ref15","volume-title":"Measuring Intelligence of Indian Children. 4th ed","author":"V V Kamat","year":"1968"},{"issue":"06","key":"ref16","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1007\/s11011-020-00554-x","article-title":"Molecular and biochemical study of glutaric aciduria type 1 in 49 Russian families: nine novel mutations in the GCDH gene","volume":"35","author":"M V Kurkina","year":"2020","journal-title":"Metab Brain Dis"},{"issue":"04","key":"ref17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S1096-7192(03)00109-4","article-title":"Pathogenic mutations in the carboxyl-terminal domain of glutaryl-CoA dehydrogenase: effects on catalytic activity and the stability of the tetramer","volume":"79","author":"J B Westover","year":"2003","journal-title":"Mol Genet Metab"},{"issue":"42","key":"ref18","doi-asserted-by":"crossref","first-page":"13932","DOI":"10.1021\/bi050525+","article-title":"Protonation of crotonyl-CoA dienolate by human glutaryl-CoA dehydrogenase occurs by solvent-derived protons","volume":"44","author":"K S Rao","year":"2005","journal-title":"Biochemistry"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ymgme.2010.11.159","article-title":"Clinical and molecular investigation of 19 Japanese cases of glutaric acidemia type 1","volume":"102","author":"Y Mushimoto","year":"2011","journal-title":"Mol Genet Metab"},{"issue":"04","key":"ref20","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s11011-019-00422-3","article-title":"Clinical, biochemical, neuroradiological and molecular characterization of Egyptian patients with glutaric acidemia type 1","volume":"34","author":"H Zayed","year":"2019","journal-title":"Metab Brain Dis"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/8904_2014_377","article-title":"Glutaric acidemia type 1-clinico-molecular profile and novel mutations in GCDH gene in indian patients","volume":"21","author":"N Gupta","year":"2015","journal-title":"JIMD Rep"},{"issue":"01","key":"ref22","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.braindev.2015.05.013","article-title":"Spectrum of mutations in glutaryl-CoA dehydrogenase gene in glutaric aciduria type I--study from South India","volume":"38","author":"A Radha Rama Devi","year":"2016","journal-title":"Brain Dev"},{"issue":"03","key":"ref23","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1055\/s-0037-1599202","article-title":"Genetic screening of selected disease-causing mutations in glutaryl-CoA dehydrogenase gene among Indian patients with glutaric aciduria type I","volume":"6","author":"K V Tp","year":"2017","journal-title":"J Pediatr Genet"},{"issue":"12","key":"ref24","doi-asserted-by":"crossref","first-page":"10021","DOI":"10.1002\/jcb.27332","article-title":"Oxidative damage in glutaric aciduria type I patients and the protective effects of l-carnitine treatment","volume":"119","author":"G Guerreiro","year":"2018","journal-title":"J Cell Biochem"},{"key":"ref25","first-page":"222","article-title":"Glutaric aciduria type 1 presenting as bilateral subdural hematomas mimicking nonaccidental trauma. Case report and review of the literature","volume":"106","author":"F S Bishop","year":"2007","journal-title":"J Neurosurg"},{"issue":"04","key":"ref26","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/mdc3.12633","article-title":"Atypical glutaric aciduria type I with hemidystonia and asymmetric radiological findings misdiagnosed as an Ischemic Stroke","volume":"5","author":"D Demailly","year":"2018","journal-title":"Mov Disord Clin Pract (Hoboken)"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4103\/0972-2327.93273","article-title":"Glutaric aciduria type I: a treatable neurometabolic disorder","volume":"15","author":"M Kamate","year":"2012","journal-title":"Ann Indian Acad Neurol"},{"issue":"04","key":"ref28","doi-asserted-by":"crossref","first-page":"e572","DOI":"10.18295\/squmj.2015.15.04.026","article-title":"Diagnosis and genetic analysis of glutaric acidaemia type I: very rarely seen inborn error of metabolism","volume":"15","author":"M Vasikarla","year":"2015","journal-title":"Sultan Qaboos Univ Med J"},{"issue":"05","key":"ref29","first-page":"695","article-title":"Antenatal diagnosis of glutaric acidemia","volume":"32","author":"S I Goodman","year":"1980","journal-title":"Am J Hum Genet"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tjog.2017.12.023","article-title":"Prenatal diagnosis of fetal glutaric aciduria type 1 with rare compound heterozygous mutations in GCDH gene","volume":"57","author":"H H Peng","year":"2018","journal-title":"Taiwan J Obstet Gynecol"},{"issue":"11","key":"ref31","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s12098-019-03017-z","article-title":"Is Expanded Newborn Screening Adequate to Detect Indian Biochemical Low Excretor Phenotype Patients of Glutaric Aciduria Type I?","volume":"86","author":"M Shaik","year":"2019","journal-title":"Indian J Pediatr"}],"container-title":["Journal of Pediatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1715528.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T19:45:48Z","timestamp":1758138348000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1715528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,2]]},"references-count":28,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2021,9,3]]},"published-print":{"date-parts":[[2021,9]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1715528","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2146-4596","2146-460X"],"issn-type":[{"value":"2146-4596","type":"print"},{"value":"2146-460X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,2]]}}}