We report a case of neonate who was clinically normal at birth and was on direct breast feeds. Evaluation was done in view of abnormal odour of urine and previous 2 sibling deaths. Baby developed symptoms in the form of vomiting and lethargy on day 7 of life. Baby had associated late onset sepsis & was treated with antibiotics. Initial baseline workup for IEM showed hyperammonia & ketoacidosis. Tandem Mass Spectrometry was suggestive of Isovaleric academia & was started on specialized formula feeds (Leucine free diet). Baby was also continued on quantified amounts of breast feeds. Baby tolerated feeds well & was discharged with leucine free diet & carnitine supplementation which promotes normal development of infant. Baby was also continued with quantified amount of mother’s milk (30 ml/kg/day). Serial monitoring of growth parameters was done which was appropriate for age and serum aminoacid levels were monitored which was normal.

Keywords:  inborn error of metabolism, isovaleric acidemia , sweaty feet odour , leucine free diet.

1. Sahai, I., Zytkowicz, T., Rao Kotthuri, S. et al. Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry: Experience of the Pilot Study in Andhra Pradesh, India. Indian J Pediatr 78, 953–960 (2011) doi:10.1007/s12098-011-0398-9.
2. Vardhan Patel, Santosh Yadav, Mohit Sahni. A Rare Case of Inborn Error of Metabolism - Isovaleric Acidemia. IAIM, 2017; 4(12): 214-217.
3. Ensenauer Regina., et al. “A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening”. The American Journal of Human Genetics 75.6 (2004): 1136- 1142.
4. Solano Alexandre F., et al. “Induction of oxidative stress by the metabolites accumulating in isovaleric acidemia in brain cortex of young rats”. Free Radical Research 42.8 (2008): 707- 715.
5. Grünert Sarah C., et al. “Clinical and neurocognitive outcome in symptomatic isovaleric acidemia”. Orphanet Journal of Rare Diseases 7.1 (2012): 9.
6. Couce María L., et al. “Genotype and phenotype characterization in a Spanish cohort with isovaleric acidemia”. Journal of human genetics 62.3 (2017): 355-360.
7. Ensenauer Regina., et al. “A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening”. The American Journal of Human Genetics 75.6 (2004): 1136- 1142.
8. Tanaka K., et al. “Isovaleric acidemia: a new genetic defect of leucine metabolism”. Proceedings of the National Academy of Sciences of the United States of America 56.1 (1966): 236-242.
9. G. Anthony, B.J. McDaniel, R.L. Byerley, B.C. McGrath, D.R. Cavener, M.A. McNurlan, R.C. Wek, Preservation of liver protein synthesis during dietary leucine deprivation occurs at the expense of skeletal muscle mass in mice deleted for eIF2 kinase GCN2, J. Biol. Chem. 279 (2004) 36553–36561.
10. Zhu, S.M. Krasnow, Q.R. Roth-Carter, P.R. Levasseur, T.P. Braun, A.J. Grossberg, D.L. Marks, Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency, Am. J. Physiol. Endocrinol. Metab. 303 (2012) E1446–E1458.
11. European Registry and network for introduction type metabolic diseases (E-IMD), Isovaleric Acidemia: Quick Reference Guide, 2014 http://www.e-imd.org/rc/e-imd/ htm/Article/2014/e-imd-20140716-085102 695/src/htm_fullText/en/IVA%20guideline_Quick%20reference%20guide_Ensenauer_201408.pdf (accessed 27.01.17).
12. Protein and amino acid requirements in human nutrition, World Health Organization Technical Report series, 2007, pp. 1–265
13. Ensenauer, J. Vockley, J.M. Willard, J.C. Huey, J.O. Sass, S.D. Edland, B.K. Burton, S.A. Berry, R. Santer, S. Grunert, H.G. Koch, I. Marquardt, P. Rinaldo, S. Hahn, D. Matern, A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening, Am. J. Hum. Genet. 75 (2004) 1136–1142.

Dr Poola Srikanth

Post Graduate, Department of Pediatrics, Chettinad Hospital & Research Institute, Chettinad Academy of Research & Education