Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations.
Mitochondrial disorders can be linked to mutations in both mitochondrial and nuclear deoxyribonucleic acid, corresponding to various clinical phenotypes. Mutations in nuclear genes, including NDUFV1, have been associated with severe encephalomyopathies in infants, but genotype-phenotype correlations have remained elusive. This report details the complete clinical, biochemical, and molecular data of a 7-year-old male who presented at the age of 7 months with progressive ophthalmoplegia and later developed cerebellar ataxia, spasticity, and dystonia. Complex I deficiency was demonstrated in muscle, and two pathogenic missense mutations were present in the NDUFV1 gene. Ketogenic diet has seemingly improved the oculomotor palsy but has been unable to correct other neurologic symptoms. Considering other cases from the literature, this report broadens our understanding of genotype-phenotype correlations for NDUFV1 mutations and illustrates a potential and partial efficacy of ketogenic diet in complex I deficient patients.
Laugel
Vincent
V
Department of Pediatrics, Strasbourg University Hospital, Strasbourg, France. vincent.laugel@chru-strasbourg.fr <vincent.laugel@chru-strasbourg.fr>
This-Bernd
Valérie
V
Cormier-Daire
Valérie
V
Speeg-Schatz
Claude
C
de Saint-Martin
Anne
A
Fischbach
Michel
M
D017668:Age of Onset; D042967:Electron Transport Complex I / Q000172:deficiency*; D005838:Genotype; D006801:Humans; D007223:Infant; D007662:Ketosis; D007888:Leigh Disease / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D009245:NADH Dehydrogenase / Q000235:genetics*; D009886:Ophthalmoplegia / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype
C112232:NDUFV1 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I