Leigh Syndrome Followed by Parkinsonism in an Adult with Homozygous C.626C>T Mutation in

Overview

Journal Neurol Genet

Date 2018 Dec 21

PMID 30569017

Citations 3

Authors

Dimitri M Hemelsoet

Arnaud V Vanlander

Joel Smet

Elise Vantroys

Marjan Acou

Ingeborg Goethals

Tom Sante

Sara Seneca

Bjorn Menten

Rudy Van Coster

Affiliations

Soon will be listed here.

Abstract

Objective: To report the clinical, radiologic, biochemical, and molecular characteristics in a 46-year-old participant with adult-onset Leigh syndrome (LS), followed by parkinsonism.

Methods: Case description with diagnostic workup included blood and CSF analysis, skeletal muscle investigations, blue native polyacrylamide gel electrophoresis, whole exome sequencing targeting nuclear genes involved in mitochondrial transcription and translation, cerebral MRI, 123I-FP-CIT brain single-photon emission computed tomography (SPECT), and C-11 raclopride positron emission tomography (PET).

Results: The participant was found to have a defect in the oxidative phosphorylation caused by a c.626C>T mutation in the gene coding for mitochondrial methionyl-tRNA formyltransferase (), which is a pathogenic mutation affecting intramitochondrial protein translation. The proband had a normal concentration of lactate in blood and no abnormal microscopic findings in skeletal muscle. Cerebral MRI showed bilateral lesions in the striatum, mesencephalon, pons, and medial thalamus. Lactate concentration in CSF was increased. FP-CIT SPECT and C-11 raclopride PET demonstrated a defect in the dopaminergic system.

Conclusions: We report on a case with adult-onset LS related to a mutation. Two years after the onset of symptoms of LS, the proband developed a parkinson-like disease. The c.626C>T mutation is the most common pathogenic mutation found in 22 patients reported earlier in the literature with a defect in . The age of the previously reported cases varied between 14 months and 24 years. Our report expands the phenotypical spectrum of -related neurologic disease and provides clinical evidence for involvement of in extrapyramidal syndromes.

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