Introduction

Mitochondrial diseases represent one of the most heterogeneous group of metabolic disorders. These disorders can manifest at any age, presenting involving isolated or multiple-organ involvement. Next-generation sequencing have greatly enhanced the diagnosis of patients with rare mitochondrial diseases. It has often revealed the novel pathogenic mutations widening the spectrum of these group of disorders. Here we describe a infant presenting with early mitochondrial syndrome with 3 methylglutaconic aciduria .

Case

A four month old boy born out of non consanguineous marriage presented with early infinite onset epileptic encephalopathy in the form of epileptic spasms, fragmentary myoclonus, hyptonia, extrapyramidal movements, neuropenia and encephalopathy. His MRI brain was normal and EEG showed burst suppression pattern favoring early myoclonic epilepsy(EME).His metabolic evaluation revealed 3 methyl glutaconic aciduria.family’s frist previous child agirl was affected with same clinical syndrome and died at 5 months of age without any conclusive diagnosis. This child’s clinical exome sequencing revealed a homozygous novel mutation chr2:74757135T>C (Hom);c.2T>C; p.Met1 in  exon 1 of HTRA2 gene. Both the parents were found to bearing the same mutation in heterozygous state confirming its pathogenicity.

Conclusion

The primary function of HTRA2 in mitochondria is to maintain mitochondrial protein homeostasis. Our findings report a novel pathogenic variant of HTRA2 gene and should be consider in any child presenting with rapidly progressive early infantile onset mitochondrial disorders presenting with seizures, encephalopathy, neutropenia and movement disorder.3 methyl glutaconic aciduria can be seen as useful biomarker to screen for HTRA2 gene in affected children.