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Chronic intermittent form of isovaleric aciduria in a 2-year-old boy

  • Cho, Jin Min (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Lee, Beom Hee (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Gu-Hwan (Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Yoo-Mi (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Choi, Jin-Ho (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
  • Received : 2012.08.24
  • Accepted : 2012.09.26
  • Published : 2013.08.15

Abstract

Isovaleric aciduria (IVA) is caused by an autosomal recessive deficiency of isovaleryl-CoA dehydrogenase (IVD). IVA presents either in the neonatal period as an acute episode of fulminant metabolic acidosis, which may lead to coma or death, or later as a "chronic intermittent form" that is associated with developmental delays, with or without recurrent acidotic episodes during periods of stress, such as infections. Here, we report the case of a 2-year old boy with IVA who presented with the chronic intermittent form. He was admitted to Asan Medical Center Children's Hospital with recurrent vomiting. Metabolic acidosis, hyperammonemia, elevated serum lactate and isovalerylcarnitine levels, and markedly increased urine isovalerylglycine concentration were noted. Sequence analysis of the IVD gene in the patient revealed the novel compound mutations-a missense mutation, c.986T>C (p.Met329Thr) and a frameshift mutation, c.1083del (p.Ile361fs$^*11$). Following stabilization during the acute phase, the patient has remained in a stable condition on a low-leucine diet.

Keywords

References

  1. Tanaka K, Budd MA, Efron ML, Isselbacher KJ. Isovaleric acidemia: a new genetic defect of leucine metabolism. Proc Natl Acad Sci U S A 1966;56:236-42. https://doi.org/10.1073/pnas.56.1.236
  2. Vockley J, Ensenauer R. Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity. Am J Med Genet C Semin Med Genet 2006;142C:95-103. https://doi.org/10.1002/ajmg.c.30089
  3. Grunert SC, Wendel U, Lindner M, Leichsenring M, Schwab KO, Vockley J, et al. Clinical and neurocognitive outcome in symptomatic isovaleric acidemia. Orphanet J Rare Dis 2012;7:9. https://doi.org/10.1186/1750-1172-7-9
  4. Dionisi-Vici C, Deodato F, Roschinger W, Rhead W, Wilcken B. 'Classical' organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis 2006;29:383-9. https://doi.org/10.1007/s10545-006-0278-z
  5. Dercksen M, Duran M, Ijlst L, Mienie LJ, Reinecke CJ, Ruiter JP, et al. Clinical variability of isovaleric acidemia in a genetically homogeneous population. J Inherit Metab Dis 2012;35:1021-9. https://doi.org/10.1007/s10545-012-9457-2
  6. Tajima G, Sakura N, Yofune H, Dwi Bahagia Febriani A, Nishimura Y, Sakamoto A, et al. Establishment of a practical enzymatic assay method for determination of isovaleryl-CoA dehydrogenase activity using high-performance liquid chromatography. Clin Chim Acta 2005;353:193-9. https://doi.org/10.1016/j.cccn.2004.11.007
  7. Frerman FE, Goodman SI. Fluorometric assay of acyl-CoA dehydrogenases in normal and mutant human fibroblasts. Biochem Med 1985;33:38-44. https://doi.org/10.1016/0006-2944(85)90124-3
  8. Hyman DB, Tanaka K. Isovaleryl-CoA dehydrogenase activity in isovaleric acidemia fibroblasts using an improved tritium release assay. Pediatr Res 1986;20:59-61. https://doi.org/10.1203/00006450-198601000-00017
  9. Parimoo B, Tanaka K. Structural organization of the human isovaleryl- CoA dehydrogenase gene. Genomics 1993;15:582-90. https://doi.org/10.1006/geno.1993.1111
  10. Ensenauer R, Vockley J, Willard JM, Huey JC, Sass JO, Edland SD, et al. A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. Am J Hum Genet 2004;75:1136-42. https://doi.org/10.1086/426318
  11. Lee HJ. Organic acidemias in Korea. Hanyang Med Rev 2005;25: 49-64.
  12. Cheon KS, Lee DH. Isovaleric acidemia in siblings diagnosed by organic acid analysis. J Korean Pediatr Soc 2000;43:828-31.
  13. Lee YW, Lee DH, Vockley J, Kim ND, Lee YK, Ki CS. Different spectrum of mutations of isovaleryl-CoA dehydrogenase (IVD) gene in Korean patients with isovaleric acidemia. Mol Genet Metab 2007; 92:71-7. https://doi.org/10.1016/j.ymgme.2007.05.003
  14. Lin WD, Wang CH, Lee CC, Lai CC, Tsai Y, Tsai FJ. Genetic mutation profile of isovaleric acidemia patients in Taiwan. Mol Genet Metab 2007;90:134-9. https://doi.org/10.1016/j.ymgme.2006.08.011
  15. Ensenauer R, Fingerhut R, Maier EM, Polanetz R, Olgemoller B, Roschinger W, et al. Newborn screening for isovaleric acidemia using tandem mass spectrometry: data from 1.6 million newborns. Clin Chem 2011;57:623-6. https://doi.org/10.1373/clinchem.2010.151134

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