medigraphic.com
Órgano Oficial del Instituto Nacional de Pediatría

2023, Number 4

<< Back Next >>

Acta Pediatr Mex 2023; 44 (4)

Glutaric aciduria type I: Report of a late diagnosed case

López RVRJ, Chima GMC, Parra GLM, Navarro EM, Santillán HY, Vargas QÉ

Language: Spanish
References: 35
Page: 290-296
PDF size: 454.06 Kb.


ABSTRACT

Background: Glutaric aciduria type I (AG-I) is an inborn error of metabolism caused by variants in GCDH, this affects the function of the enzyme glutaryl-CoA dehydrogenase and produces accumulation of neurotoxic metabolites, patients with this disfunction are characterized with striatal lesions and movement disorders (dystonia, choreoathetosis).
Case Report: The patient is a 3-year-old Mexican male with a history of an encephalopathic crisis at 10 months old, after this episode he suffered development regression, hypotonia and movement disorder, he has also other pathological antecedents: laryngomalacia, recurrent hordeolum, chronic productive cough, diarrhea-constipation, generalized hyperhidrosis and multiple hospitalizations for acute respiratory infections. MRI reported expansion in the frontotemporal subarachnoid space and the Sylvian fissures, also bilateral atrophy, T2/FLAIR hyperintensity and restricted diffusion in the basal ganglia; organic acids analysis showed increased glutaric acid levels; GCDH sequencing reported two pathogenic variants: p.Arg402Trp and p.Thr429Met.
Conclusions: This is a report of a late diagnosed AG-I case with two pathogenic variants in GCDH, previously unreported in the Mexican population. Early AG-I treatment radically changes the prognosis; however, it depends on screening methods for diagnosis that are not widely available in some populations.


REFERENCES

  1. Lindner M, Kölker S, Schulze A, Christensen E, GreenbergCR, Hoffmann GF. Neonatal screening for glutaryl-CoAdehydrogenase deficiency. J Inherit Metab Dis 2004; 27:851-9.

  2. Hedlund GL, Longo N, Pasquali M. Glutaric acidemia type1. Am J Med Genet C Semin Med Genet 2006; 142C (2):86-94.

  3. Boy N, Mühlhausen C, Maier EM, Heringer J, Assmann B,Burgard P, et al. Proposed recommendations for diagnosingand managing individuals with glutaric aciduria type I:second revision. J Inherit Metab Dis 2017; 40 (1): 75-101.

  4. Kölker S, Garbade S, Greenberg C, Leonard J, SaudubrayJM, Ribes A, et al. Natural history, outcome, and treatmentefficacy in children and adults with glutaryl-coa dehydrogenasedeficiency. Pediatr Res 2006; 59 (6): 840-7.

  5. Bjugstad KB, Goodman SI, Freed CR. Age at symptom onsetpredicts severity of motor impairment and clinical onsetof glutaric aciduria type I. J Pediatr 2000; 137 (5): 681-86.

  6. McClelland VM, Bakalinova DB, Hendriksz C, Singh RP.Glutaric aciduria type 1 presenting with epilepsy. Dev MedChild Neurol 2009; 51 (3): 235-39.

  7. Kölker S, Garcia-Cazorla A, Valayannopoulos V, Lund A, BurlinaA, Sykut-Cegielska J, et al. The phenotypic spectrum oforganic acidurias and urea cycle disorders. Part 1: the initialpresentation. J Inherit Metab Dis 2015; 38 (6): 1041-57.

  8. Hoffmann GF, Athanassopoulos S, Burlina AB, Duran M, deKlerk JB, Lehnert W, et al. Clinical course, early diagnosis,treatment, and prevention of disease in glutaryl-CoAdehydrogenase deficiency. Neuropediatrics 1996; 27 (3):115-23.

  9. Kafil-Hussain NA, Monavari A, Bowell R, Thornton P,Naughten E, O'Keefe M. Ocular findings in glutaric aciduriatype 1. J Pediatr Ophthalmol Strabismus 2000; 37(5): 289-93.

  10. Kölker S, Valayannopoulos V, Burlina AB, Sykut-Cegielska J,Wijburg FA, Leăo-Teles E, et al. The phenotypic spectrumof organic acidurias and urea cycle disorders. Part 2: theevolving clinical phenotype. J Inherit Metab Dis 2015; 38:1059-1074.

  11. Brismar J, Ozand PT. CT and MR of the brain in glutaricacidemia type I: a review of 59 published cases and areport of 5 new patients. AJNR Am J Neuroradiol 1995;16 (4): 675-83.

  12. Vester ME, Bilo RA, Karst WA, Daams JG, Duijst WL, vanRijn RR. Subdural hematomas: glutaric aciduria type 1 orabusive head trauma? A systematic review. Forensic SciMed Pathol 2015; 11 (3): 405-415.

  13. Bähr O, Mader I, Zschocke J, Dichgans J, Schulz JB. Adultonset glutaric aciduria type I presenting with leukoencephalopathy.Neurology 2002; 59: 1802-1804.

  14. Külkens S, Harting I, Sauer S, Zschocke J, Hoffmann GF,Gruber S, Bodamer OA, Kölker S. Late-onset neurologicdisease in glutaryl-CoA dehydrogenase deficiency. Neurology2005; 64: 2142-2144.

  15. Boy N, Heringer J, Brackmann R, Bodamer O, Seitz A, KölkerS, et al. Extrastriatal changes in patients with late-onsetglutaric aciduria type I highlight the risk of long-term neurotoxicity.Orphanet J Rare Dis 2017; 12 (1): 77.

  16. Busquets C, Merinero B, Christensen E, Gelpí JL, CampistolJ, Pineda M, et al. Glutaryl-CoA dehydrogenase deficiencyin Spain: evidence of two groups of patients, geneticallyand biochemically distinct. Pediatr Res 2000; 48: 315-322.

  17. Goodman SI, Markey SP, Moe PG, Miles BS, Teng CC. Glutaricaciduria; a "new" disorder of amino acid metabolism.Biochem Med 1975; 12 (1): 12-21.

  18. Greenberg CR, Reimer D, Singal R, Triggs-Raine B, ChudleyAE, Dilling LA, et al. A G-to-T transversion at the +5 positionof intron 1 in the glutaryl CoA dehydrogenase gene isassociated with the Island Lake variant of glutaric acidemiatype I. Hum Mol Genet 1995; 4 (3): 493-95.

  19. Kölker S, Koeller DM, Okun JG, Hoffmann GF. Pathomechanismsof neurodegeneration in glutaryl-CoA dehydrogenasedeficiency. Ann Neurol 2004; 55 (1): 7-12.

  20. Kyllerman M, Skjeldal O, Christensen E, Hagberg G, HolmeE, Lönnquist T, et al. Long-term follow-up, neurologicaloutcome and survival rate in 28 Nordic patients with glutaricaciduria type 1. Eur J Paediatr Neurol 2004; 8 (3): 121-29.

  21. Kamate M, Patil V, Chetal V, Darak P, Hattiholi V. Glutaricaciduria type I: A treatable neurometabolic disorder. AnnIndian Acad Neurol 2012; 15 (1): 31-34.

  22. Wang Q, Li X, Ding Y, Liu Y, Song J, Yang Y. Clinical and mutationalspectra of 23 Chinese patients with glutaric aciduriatype 1. Brain Dev 2014; 36 (9): 813-822.

  23. Badve MS, Bhuta S, Mcgill J. Rare presentation of a treatabledisorder: glutaric aciduria type 1. N Z Med J 2015;128 (1409): 61-64.

  24. Thomason MJ, Lord J, Bain MD, Chalmers RA, LittlejohnsP, Addison GM, et al. A systematic review of evidence forthe appropriateness of neonatal screening programmesfor inborn errors of metabolism. J Public Health Med 1998;20 (3): 331-43.

  25. Strauss KA, Puffenberger EG, Robinson DL, Morton DH.Type I glutaric aciduria, part 1: natural history of 77 patients.Am J Med Genet C Semin Med Genet 2003; 121C(1): 38-52.

  26. Naughten ER, Mayne PD, Monavari AA, Goodman SI,Sulaiman G, Croke DT. Glutaric aciduria type I: outcomein the Republic of Ireland. J Inherit Metab Dis 2004; 27(6): 917-20.

  27. Kölker S, Garbade SF, Boy N, Maier EM, Meissner T, MühlhausenC, et al. Decline of acute encephalopathic crisesin children with glutaryl-CoA dehydrogenase deficiencyidentified by newborn screening in Germany. Pediatr Res2007; 62 (3): 357-63.

  28. Bijarnia S, Wiley V, Carpenter K, Christodoulou J, EllawayCJ, Wilcken B. Glutaric aciduria type I: outcome followingdetection by newborn screening. J Inherit Metab Dis 2008;31 (4): 503-507.

  29. Viau K, Ernst SL, Vanzo RJ, Botto LD, Pasquali M, LongoN. Glutaric acidemia type 1: outcomes before and afterexpanded newborn screening. Mol Genet Metab 2012;106 (4): 430-38.

  30. Campos-García FJ, Chacón-Camacho OF, Contreras-CapetilloS, Cruz-Aguilar M, Medina-Escobedo CE, Moreno-GracianoCM, et al. Characterization of novel GCDH pathogenicvariants causing glutaric aciduria type 1 in the southeast ofMexico. Mol Genet Metab Rep 2019; 21: 100533.

  31. Biery BJ, Stein DE, Morton DH, Goodman SI. Gene structureand mutations of glutaryl-coenzyme A dehydrogenase:impaired association of enzyme subunits that is due to anA421V substitution causes glutaric acidemia type I in theAmish. Am J Hum Genet 1996; 59 (5): 1006-1011.

  32. Zschocke J, Quak E, Guldberg P, Hoffmann GF. Mutationanalysis in glutaric aciduria type I. J Med Genet 2000; 37(3): 177-81. doi:10.1136/jmg.37.3.177

  33. Busquets C, Coll MJ, Ribes A. Evidence of a single originfor the most frequent mutation (R402W) causing glutaryl-CoA dehydrogenase deficiency: identification of 3 novelpolymorphisms and haplotype definition. Hum Mutat2000; 15 (2): 207.

  34. Schwartz M, Christensen E, Superti-Furga A, Brandt NJ.The human glutaryl-CoA dehydrogenase gene: report ofintronic sequences and of 13 novel mutations causingglutaric aciduria type I. Hum Genet 1998; 102 (4): 452-58.

  35. Georgiou T, Nicolaidou P, Hadjichristou A, Ioannou R,Dionysiou M, Siama E, et al. Molecular analysis of Cypriotpatients with Glutaric aciduria type I: identification oftwo novel mutations. Clin Biochem 2014; 47 (13-14):1300-1305.




2020     |     www.medigraphic.com