European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society · 2021
The phenotypic variability and natural history of NARS2 associated disease.
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Sofou Kalliopi, Kollberg Gittan, Hedberg-Oldfors Carola, Oldfors Anders
Аннотация
INTRODUCTION: The phenotypic variability of NARS2 associated disease is vast, yet not thoroughly explored. We present the phenotypic and genetic features of 2 siblings with early-onset mitochondrial encephalopathy due to pathogenic variant in NARS2, along with the results from a systematic literature review.
AIMS: To better delineate the phenotypic variability and natural history of NARS2 associated disease.
METHODS: The clinical and radiological phenotype, along with the results from the morphological and biochemical investigations from the muscle biopsy as well as the postmortem investigations, where applicable, are presented. Genetic analysis was performed with next-generation sequencing.
RESULTS: Together with these 2 patients, we have diagnosed and followed 3 Scandinavian patients with the same homozygous p. Pro214Leu variant in NARS2 who presented with phenotypic features of early-onset mitochondrial encephalopathy and variable disease course. Another 14 patients with pathogenic variants in NARS2 were identified in the literature. We found that sensorineural hearing impairment is a cardinal feature of early-onset NARS2 associated disease, either isolated or in combination with central nervous system disease. Early-onset mitochondrial encephalopathy due to NARS2 variants shared phenotypic features of Alpers or Leigh syndrome and was characterized by more severe disease course and poorer survival compared to the other NARS2 associated phenotypes.
CONCLUSION: NARS2 variants present with a spectrum of clinical severity from a severe, infantile-onset, progressive disease to a mild, non-progressive disease, without strong association between the genotype and the disease outcome.
AIMS: To better delineate the phenotypic variability and natural history of NARS2 associated disease.
METHODS: The clinical and radiological phenotype, along with the results from the morphological and biochemical investigations from the muscle biopsy as well as the postmortem investigations, where applicable, are presented. Genetic analysis was performed with next-generation sequencing.
RESULTS: Together with these 2 patients, we have diagnosed and followed 3 Scandinavian patients with the same homozygous p. Pro214Leu variant in NARS2 who presented with phenotypic features of early-onset mitochondrial encephalopathy and variable disease course. Another 14 patients with pathogenic variants in NARS2 were identified in the literature. We found that sensorineural hearing impairment is a cardinal feature of early-onset NARS2 associated disease, either isolated or in combination with central nervous system disease. Early-onset mitochondrial encephalopathy due to NARS2 variants shared phenotypic features of Alpers or Leigh syndrome and was characterized by more severe disease course and poorer survival compared to the other NARS2 associated phenotypes.
CONCLUSION: NARS2 variants present with a spectrum of clinical severity from a severe, infantile-onset, progressive disease to a mild, non-progressive disease, without strong association between the genotype and the disease outcome.