Juvenile parkinsonism, hypogonadism and Leigh-like MRI changes in a patient with m.4296G>A mutation in mitochondrial DNA

Leigh syndrome is a mitochondrial disease with considerable clinical and genetic variation. We present a 16-year-old boy with Leigh-like syndrome and broad developmental retardation, parkinsonism and hypogonadism. Sequencing of the entire mitochondrial DNA from blood revealed the m.4296G>A mutation in the MT-TI gene. The mutation was heteroplasmic with a 95% proportion of the mutant genome, while the proportion was 58% in the blood of the patient's clinically healthy mother. Our results suggest that m.4296G>A is pathogenic in humans, and that the phenotype related to this change includes Leigh-like syndrome in adolescence with parkinsonism and hypogonadism, in addition to the previously reported early infantile Leigh syndrome.

► Leigh syndrome is a mitochondrial disease with large clinical and genetic variation.
► A 16-year-old boy presented with Leigh-like syndrome, parkinsonism and hypogonadism.
► Sequencing of the entire mtDNA revealed the m.4296G>A mutation in the MT-TI gene.
► We suggest that the m.4296G>A mutation is pathogenic and causes Leigh-like syndrome.