Abstract
Isovaleric acidemia is a rare autosomal recessive inborn error of leucine catabolism caused by deficiency of isovaleryl coenzyme A dehydrogenase. This enzymatic deficiency leads to severe metabolic derangement, manifested clinically as vomiting, dehydration, and acidosis progressing to seizures, coma, and death. The two phenotypic expressions are the acute severe and the chronic intermittent form. The acute severe phenotype typically results in death during early infancy, whereas patients with the chronic intermittent form are asymptomatic at baseline but have episodes of acute metabolic decompensation, usually in the setting of infection, physical exertion, or ingestion of protein-rich food. This case illustrates how inborn errors of metabolism resulting in organic acidemia can be manifested in adults and why the internist needs to be aware of them.
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References
References 1. Mayatepek E, Kurczynski TW, Hoppel CL. Long-term l -carnitine treatment in isovaleric acidemia. Pediatr Neurol 1991; 7: 137–140.MayatepekE]]KurczynskiTW]]HoppelCLLong-terml-carnitine treatment in isovaleric acidemiaPediatr Neurol19917137 2. Berry GT, Yudkoff M, Segal S. Isovaleric acidemia: Medical and neurodevelopmental effects of long-term therapy. J Pediatr 1988; 113: 58–64.BerryGT]]YudkoffM]]SegalSIsovaleric acidemia: Medical and neurodevelopmental effects of long-term therapyJ Pediatr198811358 3. Weinberg GL, Laurito CE, Geldner P, Pygon BH, Burton BK. Malignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. J Clin Anesth 1997; 9: 668–670.WeinbergGL]]LauritoCE]]GeldnerP]]PygonBH]]BurtonBKMalignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomyJ Clin Anesth19979668 4. Shih VE, Aubry RH, DeGrande G, Gursky SF, Tanaka K. Maternal isovaleric acidemia. J Pediatr 1984; 105: 77–78.ShihVE]]AubryRH]]DeGrandeG]]GurskySF]]TanakaKMaternal isovaleric acidemiaJ Pediatr198410577 DeGowin RL. DeGowin and DeGowin's Diagnostic Examination. New York, McGraw-Hill, 1987, ed 6, p 197. 6. 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: 236–242.TanakaK]]BuddMA]]EfronML]]IsselbacherKJIsovaleric acidemia: A new genetic defect of leucine metabolismProc Natl Acad Sci U S A196656236 7. Budd MA, Tanaka K, Holmes LB, Efron ML, Crawford JD, Isselbacher KJ. Isovaleric acidemia: Clinical features of a new genetic defect of leucine metabolism. N Engl J Med 1967; 277: 321–327.BuddMA]]TanakaK]]HolmesLB]]EfronML]]CrawfordJD]]IsselbacherKJIsovaleric acidemia: Clinical features of a new genetic defect of leucine metabolismN Engl J Med1967277321 8. Scriver CR, Beaudet AL, Valle D, Sly WS, Childs B, Kinzler KW, et al (eds). The Metabolic and Molecular Bases of Inherited Disease. New York, McGraw-Hill, 2001, vol 2, ed 8, pp 2130–2138. 9. Hyman DB, Tanaka K. Isovaleryl-CoA dehydrogenase activity in isovaleric acidemia fibroblasts using an improved tritium release assay. Pediatr Res 1986; 20: 59–61.HymanDB]]TanakaKIsovaleryl-CoA dehydrogenase activity in isovaleric acidemia fibroblasts using an improved tritium release assayPediatr Res19862059 10. Lott IT, Erickson AM, Levy HL. Dietary treatment of an infant with isovaleric acidemia. Pediatrics 1972; 49: 616–618.LottIT]]EricksonAM]]LevyHLDietary treatment of an infant with isovaleric acidemiaPediatrics197249616 11. Levy HL, Erickson AM, Lott IT, Kurtz DJ. Isovaleric acidemia: Results of family study and dietary treatment. Pediatrics 1973; 52: 83–94.LevyHL]]EricksonAM]]LottIT]]KurtzDJIsovaleric acidemia: Results of family study and dietary treatmentPediatrics19735283 12. Millington DS, Roe CR, Maltby DA, Inoue F. Endogenous catabolism is the major source of toxic metabolites in isovaleric acidemia. J Pediatr 1987; 110: 56–60.MillingtonDS]]RoeCR]]MaltbyDA]]InoueFEndogenous catabolism is the major source of toxic metabolites in isovaleric acidemiaJ Pediatr198711056 13. Krieger I, Tanaka K. Therapeutic effects of glycine in isovaleric acidemia. Pediatr Res 1976; 10: 25–29.KriegerI]]TanakaKTherapeutic effects of glycine in isovaleric acidemiaPediatr Res19761025 14. Naglak M, Salvo R, Madsen K, Dembure P, Elsas L. The treatment of isovaleric acidemia with glycine supplement. Pediatr Res 1988; 24: 9–13.NaglakM]]SalvoR]]MadsenK]]DembureP]]ElsasLThe treatment of isovaleric acidemia with glycine supplementPediatr Res1988249 15. Itoh T, Ito T, Ohba S, Sugiyama N, Mizuguchi K, Yamaguchi S, et al. Effect of carnitine administration on glycine metabolism in patients with isovaleric acidemia: Significance of acetylcarnitine determination to estimate the proper carnitine dose. Tohoku J Exp Med 1996; 179: 101–109.ItohT]]ItoT]]OhbaS]]SugiyamaN]]MizuguchiK]]YamaguchiSEffect of carnitine administration on glycine metabolism in patients with isovaleric acidemia: Significance of acetylcarnitine determination to estimate the proper carnitine doseTohoku J Exp Med1996179101 16. Fries MH, Rinaldo P, Schmidt-Sommerfeld E, Jurecki E, Packman S. Isovaleric acidemia: Response to a leucine load after three weeks of supplementation with glycine, l -carnitine, and combined glycine-carnitine therapy. J Pediatr 1996; 129: 449–452.FriesMH]]RinaldoP]]Schmidt-SommerfeldE]]JureckiE]]PackmanSIsovaleric acidemia: Response to a leucine load after three weeks of supplementation with glycine,l-carnitine, and combined glycine-carnitine therapyJ Pediatr1996129449 17. Roe CR, Millington DS, Maltby DA, Kahler SG, Bohan TP. l -carnitine therapy in isovaleric acidemia. J Clin Invest 1984; 74: 2290–2295.RoeCR]]MillingtonDS]]MaltbyDA]]KahlerSG]]BohanTPl-carnitine therapy in isovaleric acidemiaJ Clin Invest1984742290 18. Cohn RM, Yudkoff M, Rothman R, Segal S. Isovaleric acidemia: Use of glycine therapy in neonates. N Engl J Med 1978; 299: 996–999.CohnRM]]YudkoffM]]RothmanR]]SegalSIsovaleric acidemia: Use of glycine therapy in neonatesN Engl J Med1978299996 19. Yudkoff M, Cohn RM, Puschak R, Rothman R, Segal S. Glycine therapy in isovaleric acidemia. J Pediatr 1978; 92: 813–817.YudkoffM]]CohnRM]]PuschakR]]RothmanR]]SegalSGlycine therapy in isovaleric acidemiaJ Pediatr197892813 20. Mehta KC, Zsolway K, Osterhoudt KC, Krantz I, Henretig FM, Kaplan P. Lessons from the late diagnosis of isovaleric acidemia in a five-year-old boy. J Pediatr 1996; 129: 309–310.MehtaKC]]ZsolwayK]]OsterhoudtKC]]KrantzI]]HenretigFM]]KaplanPLessons from the late diagnosis of isovaleric acidemia in a five-year-old boyJ Pediatr1996129309 Amiel J, de Lonlay P, Francannet C, Picard A, Bruel H, Rabier D, et al. Facial anomalies in d -2-hydroxyglutaric aciduria. Am J Med Genet 1999; 86: 124–129.AmielJ]]de LonlayP]]FrancannetC]]PicardA]]BruelH]]RabierDFacial anomalies ind-2-hydroxyglutaric aciduriaAm J Med Genet199986124 &NA; Mankind must put an end to war Or war will put an end to mankind. —John F. Kennedy
