Leigh-Like Course of Progressive Encephalopathy Associated with ECHS1-Mutation— A Case Report

Introduction: Mutations in ECHS1 gene have recently been reported in children with infantile Leigh-like mitochondrial disease.¹ Short-chain enoyl-CoA hydratase (ECHS1) is a mitochondrial enzyme with several functions in β-oxidation of short- and medium-chain fatty acids as well as in isoleucine and valine metabolism. We report the rare case of a patient with ECHS1 mutation presenting with severe progressive encephalopathy without manifest epilepsy.

Case Report: After an uneventful pregnancy and perinatal period, the girl developed normally during early childhood, and she started walking at the age of 14 months. At the age of 2 years, she was referred because of stiffness of gait and a tendency to fall. Most prominent clinical findings were muscular hypotonia, disturbances of coordination, choreoathetotic movements, delayed speech development, and sensorineural deafness. Serum lactate, amino acids, and organic acids were normal. At the age of 2 years, cMRI displayed abnormal signal intensity in the basal ganglia with mildly elevated lactate and choline peaks analyzed by MR spectroscopy. Analysis of muscle tissue showed normal morphology and biochemical respiratory chain enzyme activities except a significantly decreased pyruvate dehydrogenase (PDH) activity. However, mutations in genes coding for the PDH complex (PDHA1, PDHA2, and PDHX) were ruled out, as were mutations of mitochondrial DNA. Exome sequencing revealed a homozygous missense mutation in the ECHS1 gene (c.[268G > A];[583G > A]). Both parents were identified as heterozygous conductors of the mutation. Despite supportive therapy (carnitine, thiamine, riboflavin, and α lipoic acid), the girl developed severe progressive developmental impairments with generalized hypotonia and dystonia without manifestation of cerebral seizures or cardiac complications up to the age of 5 years.

Conclusions: ECHS1 gene mutations can cause Leigh-like mitochondrial encephalopathies and should be included in diagnostic work-up if mitochondrial disease is suspected.

Keywords: ECHS1, mitochondriopathy, encephalopathy, genetics.

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Reference

1 Peters H, Buck N, Wanders R, et al. ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism. Brain 2014;137(Pt 11):2903–2908