Case Series of Ethylmalonic Encephalopathy from Southern India

Vykuntaraju K. Gowda; Varunvenkat M. Srinivasan; Kapil Jetha; Kiruthiga Sugumar; Meenakshi Bhat; Sanjay K. Shivappa; Maya Bhat; Rita Christopher

doi:10.1055/s-0041-1740370

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2023; 12(03): 213-218
DOI: 10.1055/s-0041-1740370

Original Article

Case Series of Ethylmalonic Encephalopathy from Southern India

Authors

Vykuntaraju K. Gowda

¹Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
Varunvenkat M. Srinivasan

¹Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
Kapil Jetha

¹Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
Kiruthiga Sugumar

¹Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
Meenakshi Bhat

²Department of Genetics, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
Sanjay K. Shivappa

³Department of Pediatric Medicine, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
Maya Bhat

⁴Department of Neuroradiology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
Rita Christopher

⁵Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India

Abstract

Ethylmalonic encephalopathy is a rare neurometabolic disorder with central nervous system involvement and vasculopathy. It is presented in infancy with developmental delay, acrocyanosis, petechiae, chronic diarrhea, and early death. This was a retrospective study of confirmed cases of ethylmalonic aciduria from a tertiary care hospital over a period of 5 years from January 2015 to December 2020. Case details including analysis of clinical history, investigations, and outcomes are presented. Of six cases, male-to-female ratio was 4:2. Mean age of presentation was 35.5 months (range: 14–83 months). Consanguinity, global developmental delay, failure to thrive, skin rashes, microcephaly, hypotonia, and exaggerated deep tendon reflexes were observed in all cases. Chronic diarrhea was presented in five cases. The serum levels of C4 carnitine and urinary levels of ethylmalonic acid were increased in all cases. Magnetic resonance imaging (MRI) of the brain showed heterogenous bilateral symmetrical changes in the basal ganglia in five cases, and in one case, MRI could not be done. Genetic testing in two cases showed a homozygous variant in ETHE1 gene. Four children died, while the other two cases showed a decreased in recurrent encephalopathies and diarrhea after starting metronidazole. All children had global developmental delay, failure to thrive, skin rashes, central hypotonia, increased C4 carnitine levels in the serum, and increased ethylmalonic acid in the urine. Chronic diarrhea, acrocyanosis, and basal ganglia change in the MRI of the brain also give important clues for diagnosis. Metronidazole is useful in preventing recurrent episodes of encephalopathy.

Keywords

ethylmalonic aciduria - purpura - chronic diarrhea - petechiae - ETHE1 gene

Full Text

References

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