Diagnosis and management of glutaric aciduria type I
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Glutaric aciduria type I (GA1) is a preventable cause of acute brain damage in early childhood, leading to a severe dystonic-dyskinetic disorder that is similar to cerebral palsy and ranges from extreme hypotonia to choreoathetosis to rigidity with spasticity. Degeneration of the putamen and caudate typically occurs between 6 and 18 months of age and is probably linked to changes in metabolic demand caused by normal maturational changes and superimposed catabolic stress. Recognition of this biochemical disorder before the brain has been injured is essential to outcome. Diagnosis depends upon the recognition of relatively nonspecific physical findings such as hypotonia, irritability and macrocephaly, and on performance of urine organic acid quantification by gas chromatography–mass spectrometry or selective searches of urine or blood specimens by tandem mass spectrometry for glutarylcarnitine. The diagnosis may also be suggested by characteristic findings on neuroimaging. In selected patients diagnosis can only be reached by enzyme assay. Specific current management by the authors of this paper includes pharmacological doses of L-carnitine, as well as dietary protein restriction. Metabolic decompensation must be treated aggressively to avoid permanent brain damage. Multicentre studies are needed to establish best methods of diagnosis and optimal therapy of this disorder.
- Amir N, Elpeleg ON, Shalev RS, Christensen E (1989) Glutaric aciduria type 1: enzymatic and neuroradiologic investigations of two kindreds. J Pediatr 114: 983-989.
- Anikster Y, Shaag A, Joseph A, et al (1996) Glutaric aciduria type I in the Arab and Jewish communities in Israel. Am J Hum Genet 59: 1012-1018.
- Barić I, Wagner L, Buckel W, Hoffmann GF (1997a) Sensitivity of free and total glutaric and 3-OH-glutaric acid measurements by stable isotope dilution-assays for the diagnosis of glutaric aciduria type I. J Inher Metab Dis 20 (supplement 1): 34.
- Barić I, Zschoke J, Merinero B, et al (1997b) Evaluation of acylcarnitine determination from Guthrie spots for the diagnosis of glutaryl-CoA dehydrogenase deficiency. 7th International Congress, Inborn Errors of Metabolism, Vienna, Austria, May 21-25 1997: Abstract P9.
- Bergman I, Finegold D, Gartner C, et al (1989) Acute profound dystonia in infants with glutaric acidemia. Pediatrics 83: 228-234.
- Biery BJ, Stein DE, Morton DH, Goodman SI (1996) Gene structure and mutations of glutaryl-CoA dehydrogenase: impaired association of enzyme subunits that is due to an A421V mutation causes glutaric acidemia type I in the Amish. Am J Hum Genet 59: 1006-1011.
- Campistol J, Ribes A, Alvarez L, Christensen E, Millington DS (1992) Glutaric aciduria type I: unusual biochemical presentation. J Pediatr 121: 83-86.
- Christensen E (1994) Prenatal diagnosis of glutaryl-CoA dehydrogenase deficiency: experi-ence using first trimester chorionic villus sampling. Prenat Diag 14: 333-336.
- Christensen E, Ribes A, Busquets C, et al (1997) Compound heterozygosity in the glutaryl-CoA dehydrogenase gene with R227P mutation in one allele is associated with no or very low free glutarate excretion. J Inher Metab Dis 20: 383-386.
- Dixon MA, Leonard JV (1992) Intercurrent illness in inborn errors of intermediary metabo-lism. Arch Dis Child 67: 1387-1391.
- Goodman SI, Frerman FE (1995) Organic acidemias due to defects in lysine oxidation: 2-ketoadipic acidemia and glutaric acidemia. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edn. New York: McGraw-Hill, 1451-1460.
- Goodman SI, Markey SP, Moe PG, Miles BS, Teng CC (1975) Glutaric aciduria: a ‘new’ disorder of amino acid metabolism. Biochem Med 12: 12-21.
- Goodman SI, Kratz LE, DiGiulio KA, et al (1995) Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild-type and mutant enzymes in Escherichia coli. Hum Mol Genet 4: 1493-1498.
- Greenberg CR, Reimer D, Singal R, et al (1995) A G-to-T transversion at the +5 position of intron 1 in the glutaryl-CoA dehydrogenase gene is associated with the Island Lake variant of glutaric acidemia type I. Hum Mol Genet 4: 493-495.
- Haworth JC, Booth FA, Chudley AE, et al (1991) Phenotypic variability in glutaric aciduria type I. J Pediatr 118: 52-58.
- Hoff mann GF, Trefz FK, Barth P, et al (1991) Glutaryl-CoA dehydrogenase deficiency: a distinct encephalopathy. Pediatrics 88: 1194-1203.
- Hoffmann GF, Athanassopoulos S, Burlina AB, et al (1996) Clinical course, early diagnosis, treatment and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuro-pediatrics 27: 115-123.
- Kyllerman M, Steen G (1980) Glutaric aciduria. A. commonÏ metabolic disorder ? Arch Fr Pediatr 37: 279.
- Kyllerman M, Skjeldal OH, Lundberg M, et al (1994) Dystonia and dyskinesia in glutaric aciduria type I: clinical heterogeneity and therapeutic considerations. Movement Dis 9: 22-30.
- Martinez-Lage JF, Casas C, Fernandez MA, Puche A, Rodriguez Costa T, Poza M (1994) Macrocephaly, dystonia and bilateral temporal arachnoid cysts: glutaric aciduria type 1. Child's Nerv Syst 10: 198-203.
- Merinero B, Perez-Cerda C, Font LM, et al (1995) Variable clinical and biochemical presen-tation of seven Spanish cases with glutaryl-CoA dehydrogenase deficiency. Neuropediatrics 26: 238-242.
- Morton DH, Bennet MJ, Seargeant LE, Nichter CA, Kelley RI (1991) Glutaric aciduria type I: a common cause of episodic encephalopathy and spastic paralysis in the Amish of Lan-caster county, Pennsylvania. Am J Med Genet 41: 89-95.
- Muntau AC, Röschinger W, Pfluger T, Enders A, Hoffmann GF (1997) Subdurale Hygrome und Hämatome im Säuglingsalter als Initialmanifestation der Glutarazidurie Typ I: Fol-genschwere Fehldiagnose als Kindesmiβhandlung. Monatsschr Kinderh 145: 646-651.
- Ogier de Baulny H, Saudubray JM (1995) Emergency treatments. In Fernandes J, Saudubray JM, Van den Berge G, eds. Inborn Metabolic Diseases. Diagnosis and Treatment, 2nd edn. Berlin: Springer-Verlag, 47-55.
- Ribes A, Riudor E, Briones P, Christensen E, Campistol J, Millington DS (1992) Significance of bound glutarate in the diagnosis of glutaric aciduria type I. J Inher Metab Dis 15: 367-370.
- Superti-Furga A, Hoffmann GF (1997) Glutaric aciduria type I (glutaryl-CoA-dehydrogenase deficiency): recent advances and unanswered questions. Eur J Pediatr 156: 821-828.
- Yamaguchi S, Orii T, Yasuda K, Yoshinori K (1987) A case of glutaric aciduria type 1 with unique abnormalities in the cerebral CT findings. T ohoku J Exp Med 151: 293-299.
- Yannicelli S, Rohr F, Warman M (1994) Nutrition support for glutaric acidemia type I. J Am Diet Assoc 94: 183-191.
- Ziadeh R, Naylor EW, Finegold D (1994) Identification of two cases of glutaric aciduria type I through routine neonatal screening using liquid secondary ionization tandem mass spec-trometry. Abstracts of the 6th International Congress on Inborn Errors of Metabolism (Milan, May 1994) W5.2.
- Diagnosis and management of glutaric aciduria type I
Journal of Inherited Metabolic Disease
Volume 21, Issue 4 , pp 326-340
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