• Mistakes are not an option: a clinical case of glutaric aciduria type 1
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Mistakes are not an option: a clinical case of glutaric aciduria type 1

PERINATOLOGY AND PEDIATRIC. UKRAINE. 2018.1(73):125-132; doi 10.15574/PP.2018.73.125

Kyryllova L. H., Yuzva О. О., Miroshnikov О. О., Mikhailets L. P.
SI «Institute of Pediatrics, Obstetrics and Gynaecology of NAMS of Ukraine», Kyiv, Ukraine

A review of current literature data relating to hereditary metabolic disorders — glutaric aciduria type 1 is represented in the article. The presented clinical case illustrates the complexity of diagnostic search and treatment features of this disease. The special focus is also placed on the need for vigilance of clinicians concerning early detection of potentially curable orphane diseases of the nervous system.
Key words: glutaric aciduria, seizures, glutaryl-coenzyme A dehydrogenase.


1. Aicardi J. (2009). Diseases of the nervous system in childhood. 3-rd edition. MacKeith Press: 298–300.

2. Al-Dirbashi OY, Kolker S et al. (2011). Diagnosis of glutaric aciduria type I by measuring 3-hydroxyglutaric acid in dried urine spots by liquid chromatography tandem mass spectrometry. J Inherit Metab Dis. 34 (1): 173–80. https://doi.org/10.1007/s10545-010-9223-2; PMid:20978942

3. Bjugstad KB, Goodman SL et al. (2000). Age at symptom onset predicts severity of motor impairment and clinical outcome of glutaric academia type I. J Pediatr. 137: 681–6. https://doi.org/10.1067/mpd.2000.108954; PMid:11060535

4. Boy N, Heringer J et al. (2015). A croos-sectional controlled developmental study of neuropsyhological functions in patients with glutaric aciduria type I. Orphanet J Rare Dis. 10 (1): 163. https://doi.org/10.1186/s13023-015-0379-6; PMid:26693825 PMCid:PMC4689061

5. Boy N, Muhlhausen C et al. (2017). Proposed recommendations for diagnosis and managing individuals with glutaric academia type I: second revision. J Inherit Metab Dis. 40 (1): 75–101. https://doi.org/10.1007/s10545-016-9999-9; PMid:27853989

6. Braissant O, Jafari P et al. (2017). Immunolocalization of glutaryl CoA dehydrogenase (GCDH) in adult and embryonic rat brain and peripheral tissues. Neuroscience. 343: 355–63. https://doi.org/10.1016/j.neuroscience.2016.10.049; PMid:27984186

7. Cerisola A, Campistol J et al. (2009). Seizures versus dystonia in encephalopathic crisis of glutaric aciduria type I. Pediatr Neurol. 40 (6): 426–31. https://doi.org/10.1016/j.pediatrneurol.2008.12.009; PMid:19433275

8. Chalmers RA, Bain MD et al. (2006). Riboflavin-responsive glutaryl-CoA dehydrogenase deficiency. Mol Genet Metab. 88: 29–37. https://doi.org/10.1016/j.ymgme.2005.11.007; PMid:16377226

9. Fu Z, Wang M et al. (2004). Crystal structures of human glytaryl-CoA dehydrogenase with and without an alternate substrate: structural bases of dehydrogenation and decarboxylation reactions. Biochemistry. 43 (30): 9674–84. https://doi.org/10.1021/bi049290c; PMid:15274622

10. Funk CB, Prasad AN et al. (2005). Neuropathological, biochemical and molecular findings in glutaric academia type I cohort. Brain J Neurol. 128: 711–722. https://doi.org/10.1093/brain/awh401; PMid:15689364

11. Gallagher RC, Cowan TM et al. (2005). Glutaryl-CoA dehydrogenase  deficiency and newborn screening: Retrospective analysis of a low excretor provides further evidence that some cases may be missed. Mol Genet Metab. 86 (3): 417–20. https://doi.org/10.1016/j.ymgme.2005.08.005; PMid:16183314

12. Gitiaux C, Rose E et al. (2008). Spectrum of movement disorders associated with glutaric aciduria type I: A study of 16 patients. Mov Disord. 23 (16): 2392–7. https://doi.org/10.1002/mds.22313; PMid:18823014

13. Goodman Sl et al. (1975). Glutaric aciduria: a new disorder of amino acid methabolism. Biochem Med. 12: 12—21. https://doi.org/10.1016/0006-2944(75)90091-5

14. Greenberg CR, Duncan AM et al. (1994). Assignment of human glytaryl-CoA dehydrogenase gene (GCDH) to the short arm of chromosome 19(19p13.2) by in situ hybridization and somatic cell hybrid analysis. Genomics. 21: 289—90. https://doi.org/10.1006/geno.1994.1264; PMid:8088809

15. Harting I, Boy N et al. (2015). H-HRS in glutaric aciduria type 1: impact of biochemical phenotype and age on the cerebral accumulation of neurotoxic metabolites. J Inherit Metab Dis. 38 (5): 829—38. https://doi.org/10.1007/s10545-015-9826-8; PMid:25860816

16. Harting I, Neumaier-Probst E et al. (2009). Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I. Brain. 132 (7): 1764—82. https://doi.org/10.1093/brain/awp112; PMid:19433437

17. Heringer J, Boy SP et al. (2010). Use of guidelines improves the neurological outcome in glutaric aciduria type I. Ann Neurol. 68 (5): 743—52. https://doi.org/10.1002/ana.22095; PMid:21031586

18. Herscovitz M, Goldsher D et al. (2013). Subependymal mass lesions and peripheral polyneuropathy an adult-onset glutaric aciduria type I. Neurology. 81 (9): 849—50. https://doi.org/10.1212/WNL.0b013e3182a2cbf2; PMid:23884036

19. Kolker S, Christensen E et al. (2007). Guideline for the diagnosis and management of glutaryl-CoA dehydrihenase deficiency (glutaric aciduria type I). J Inherit Metab Dis. 30 (1): 5—12. https://doi.org/10.1007/s10545-006-0451-4; PMid:17203377

20. Kolker S, Garbade SF et al. (2006). Natural history, outcome and treatmrnt efficacy in children and adults with glutaril-CoA dehydrogenase deficiency. Pediatr Res. 59 (6): 840—7. https://doi.org/10.1203/01.pdr.0000219387.79887.86; PMid:16641220

21. Kolker S, Koeller DM et al. (2004). Pathomechanisms of neurodegeneration in glutaryl-CoA dehydrogenase deficiency. Ann Neurol. 55 (1): 7—12. https://doi.org/10.1002/ana.10784; PMid:14705106

22. Kolker S, Valayannopoulus V et al. (2015, Nov). The phenotipyc spectrum of organic acidurias and urea cycle disorders. Part 2. The evolving clinical phenotype. J Inheryt Metab Dis. 38(6): 1059—74. https://doi.org/10.1007/s10545-015-9867-z; https://doi.org/10.1007/s10545-015-9839-3; https://doi.org/10.1007/s10545-015-9840-x; https://doi.org/10.1007/s10545-015-9868-y

23. Kulkens S, Harting L et al. (2005). Late-onset neurologic disease in glutaryl-CoA dehydrohenase deficiency. Neurology. 64: 2142—4. https://doi.org/10.1212/01.WNL.0000167428.12417.B2; PMid:15985591

24. Kyllerman M, Skjeldal O et al. (2004). Long-term folloe up, neurological outcome and survival rate in 28 Nordic patients with glutaric aciduria type I. Eur J Pediatr Neurol. 8 (3): 121—9. https://doi.org/10.1016/j.ejpn.2003.12.007; PMid:15120683

25. Lin SK et al. (2005). Novel mutations and prenatal sonographic findings of glutaric aciduria (type I) in two Taiwanese families. Prenat Diagn. 2005. 22 (8): 725—9. https://doi.org/10.1002/pd.392; PMid:12210585

26. Linder M, Kolker S et al. (2004). Neonatal screening for glutaryl-coA dehydrogenase deficiency. J. Inherit. Metab. Dis. 27, 851—859. https://doi.org/10.1023/B:BOLI.0000045769.96657.af; PMid:15505392

27. McClland VM, Bakalinova DB et al. (2009). Glutaric aciduria type I presenting with epilepsy. Dev Med Child. 30 (5): 231—39.

28. Pfeil J, Listl S et al. (2013). Newborn screening by tandem mass spectrometry for glutaric aciduria type I: a cost-effectiveness analysis. Orphanet J Rare Dis. 8 (1): 167. https://doi.org/10.1186/1750-1172-8-167; PMid:24135440 PMCid:PMC4015693

29. Rare Diseases UK. Key Statistics from the RDUK Report 'Experiences of Rare Diseases: An Insight from Patients and Families'. Available at: http://raredisease.org.uk/index.htm.

30. Sauer SW, Opp S et al. (2011). Therapeutic modulation of cerebral L-lysine metabolism in a mouse model for glutaric aciduria type I. Brain. 34: 157—70. https://doi.org/10.1093/brain/awq269; PMid:20923787

31. Strauss KA, Puffenberger C et al. (2003). Type I glutaric aciduria, part I: natural history of 77 patients. Am J Med Genet. 121: 38—52. https://doi.org/10.1002/ajmg.c.20007; PMid:12888985

32. Tortorelli S, Hahn SH et al. (2005). The urinary excretion of glutarylcarnitine is an informative tool in the biochemical diagnosis of glutaric aciduria type I. Mol Genet Metab. 84: 137—43. https://doi.org/10.1016/j.ymgme.2004.09.016; PMid:15670719

33. Twomey EL et al. (2003, Dec.). Neuroimaging findings in glutaric aciduria type 1. Pediatr Radiol. 33 (12): 823—30. https://doi.org/10.1007/s00247-003-0956-z; PMid:14534757

34. Vester ME, Bilo RA et al. (2015). Subdural hematomas: glutaric aciduria type I or abusive head trauma? A systematic review. Forensic Sci Med Pathol. 11 (3): 405—15. https://doi.org/10.1007/s12024-015-9698-0; PMid:26219480 PMCid:PMC4529472

35. Zielonka M, Braun K et al. (2015). Severe acute subdural hemorrhage in patient with glutaric aciduria type I after minor head trauma: a case report. J Child Neurol. 30 (8): 1065—9. https://doi.org/10.1177/0883073814541479; PMid:25038128

36. Zinnati WJ, Lazovic J et al. (2007). Mechanism of age-dependent susceptibility and novel treatmrnt strategy in glutaric academia type I. J Clin Invest. 117 (11): 3258—70. https://doi.org/10.1172/JCI31617; PMid:17932566 PMCid:PMC2000809

37. Zschocke J, Quak E et al. (2000). Mutation analysis in glutaric aciduria type I. J Med Genet. 37: 177—81. https://doi.org/10.1136/jmg.37.3.177; PMid:10699052 PMCid:PMC1734541