Pediatric Glutaric Aciduria Type 1: 14 Cases, Diagnosis and Management

Overview

Journal Ann Indian Acad Neurol

Specialty Neurology

Date 2021 Apr 29

PMID 33911375

Citations 3

Authors

Leema P Cornelius

Vivekasaravanan Raju

Asir Julin

Affiliations

Soon will be listed here.

Abstract

Introduction: Glutaric aciduria type I is an autosomal recessive disorder of lysine metabolism due to the defect of the enzyme glutaryl-CoA dehydrogenase. The regression of milestones following an intercurrent infection with disabling dystonia is the common presentation. We report the clinical features, diagnosis, and management of 14 south Indian children with glutaric aciduria type I.

Results: Males predominated the study (57.1%). The mean age of onset of the symptoms was 8.57 ± 3.57 months. The mean age at the time of diagnosis was 35.21 ± 48.31 months. The history of consanguinity was noted in 57.1%. Development was normal prior to the onset of acute crises in nearly three fourths. Acute crises triggered by infection followed by the regression of milestones was the major presenting feature in 10 children (71.4%). Macrocephaly was another prominent feature in an equal number. Bat's wing appearance (fronto temporal atrophy) was present in all children. Nearly 80% had moderate to severe disability in the form of dystonic movement disorder and spastic quadriparesis.

Conclusion: Glutaric aciduria type Ihas to be identified and managed early to have a better outcome.

Citing Articles

Glutaric aciduria type 1: Insights into diagnosis and neurogenetic outcomes.

Yoldas Celik M, Canda E, Yazici H, Erdem F, Yuksel Yanbolu A, Atik Altinok Y Eur J Pediatr. 2024; 184(1):72.

PMID: 39658645 DOI: 10.1007/s00431-024-05907-7.

Glutaric Aciduria Presenting With an Acute Encephalitic Crisis: A Case Report.

Patil M, Tyagi N, Avuthu O, Salunkhe S Cureus. 2024; 16(7):e65722.

PMID: 39211641 PMC: 11361468. DOI: 10.7759/cureus.65722.

Ataxia in Neurometabolic Disorders.

Kaminiow K, Rygula I, Paprocka J Metabolites. 2023; 13(1).

PMID: 36676973 PMC: 9866741. DOI: 10.3390/metabo13010047.

References

Vester M, Visser G, Wijburg F, van Spronsen F, Williams M, van Rijn R . Occurrence of subdural hematomas in Dutch glutaric aciduria type 1 patients. Eur J Pediatr. 2016; 175(7):1001-6. PMC: 4908155. DOI: 10.1007/s00431-016-2734-6. View

Kolker S, Garcia-Cazorla A, Cazorla A, Valayannopoulos V, Lund A, Burlina A . The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis. 2015; 38(6):1041-57. DOI: 10.1007/s10545-015-9839-3. View

Harting I, Neumaier-Probst E, Seitz A, Maier E, Assmann B, Baric I . Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I. Brain. 2009; 132(Pt 7):1764-82. DOI: 10.1093/brain/awp112. View

Strauss K, Puffenberger E, Robinson D, Morton D . Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet C Semin Med Genet. 2003; 121C(1):38-52. DOI: 10.1002/ajmg.c.20007. View

Neumaier-Probst E, Harting I, Seitz A, Ding C, Kolker S . Neuroradiological findings in glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency). J Inherit Metab Dis. 2004; 27(6):869-76. DOI: 10.1023/B:BOLI.0000045771.66300.2a. View

Lindner M, Kolker S, Schulze A, Christensen E, Greenberg C, Hoffmann G . Neonatal screening for glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004; 27(6):851-9. DOI: 10.1023/B:BOLI.0000045769.96657.af. View

Chace D, Kalas T, Naylor E . Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem. 2003; 49(11):1797-817. DOI: 10.1373/clinchem.2003.022178. View

Kamate M, Patil V, Chetal V, Darak P, Hattiholi V . Glutaric aciduria type I: A treatable neurometabolic disorder. Ann Indian Acad Neurol. 2012; 15(1):31-4. PMC: 3299068. DOI: 10.4103/0972-2327.93273. View

Hoffmann G, Trefz F, Barth P, Bohles H, Biggemann B, Bremer H . Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy. Pediatrics. 1991; 88(6):1194-203. View

10.

Kolker S, Valayannopoulos V, Burlina A, Sykut-Cegielska J, Wijburg F, Leao Teles E . The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. J Inherit Metab Dis. 2015; 38(6):1059-74. DOI: 10.1007/s10545-015-9840-x. View

11.

Boy N, Muhlhausen C, Maier E, Heringer J, Assmann B, Burgard P . Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision. J Inherit Metab Dis. 2016; 40(1):75-101. DOI: 10.1007/s10545-016-9999-9. View

12.

Martinez Granero M, Garcia Perez A, Martinez-Pardo M, Parra E . [Macrocephaly the first manifestation of glutaric aciduria type I: the importance of early diagnosis]. Neurologia. 2005; 20(5):255-60. View

13.

Zayed H, El Khayat H, Tomoum H, Khalifa O, Siddiq E, Mohammad S . Clinical, biochemical, neuroradiological and molecular characterization of Egyptian patients with glutaric acidemia type 1. Metab Brain Dis. 2019; 34(4):1231-1241. PMC: 6617250. DOI: 10.1007/s11011-019-00422-3. View

14.

Hoffmann G, Zschocke J . Glutaric aciduria type I: from clinical, biochemical and molecular diversity to successful therapy. J Inherit Metab Dis. 1999; 22(4):381-91. DOI: 10.1023/a:1005543904484. View

15.

Sarangi P, Sahoo L, Mallick A, Dash P . Glutaric Aciduria Type I: A Rare Metabolic Disorder Mimicking as Choreoathetoid Cerebral Palsy. J Pediatr Neurosci. 2017; 12(1):85-86. PMC: 5437801. DOI: 10.4103/jpn.JPN_165_16. View

16.

Kolker S, Garbade S, Greenberg C, Leonard J, Saudubray J, Ribes A . Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency. Pediatr Res. 2006; 59(6):840-7. DOI: 10.1203/01.pdr.0000219387.79887.86. View

17.

Gupta N, Singh P, Kumar M, Shastri S, Gulati S, Kumar A . Glutaric Acidemia Type 1-Clinico-Molecular Profile and Novel Mutations in GCDH Gene in Indian Patients. JIMD Rep. 2015; 21:45-55. PMC: 4470956. DOI: 10.1007/8904_2014_377. View

18.

Fu Z, Wang M, Paschke R, Rao K, Frerman F, Kim J . Crystal structures of human glutaryl-CoA dehydrogenase with and without an alternate substrate: structural bases of dehydrogenation and decarboxylation reactions. Biochemistry. 2004; 43(30):9674-84. DOI: 10.1021/bi049290c. View

19.

Mahfoud A, Dominguez C, Rizzo C, Ribes A . [In utero macrocephaly as clinical manifestation of glutaric aciduria type I. Report of a novel mutation]. Rev Neurol. 2004; 39(10):939-42. View