A new mutation in a gene called NDUFA10 was identified as the cause of mitochondria energy metabolism deficiency in a child with Leigh syndrome (LS). This is the third study reporting NDUFA10 gene involvement in LS and its impact on disease symptoms.
The case report, “Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation,” was recently published at JIMD Reports.
Leigh syndrome, the most common mitochondrial disorder in children, is an early onset and progressive neurodegenerative disease characterized by considerable clinical and genetic variability. Seventy-five genes that encode components of pathways related to energy production are reported to be associated with LS.
NDUFA10 encodes a subunit of complex I, involved in the process of oxidative phosphorylation, or OXPHOS, that is responsible for the production of energy from nutrients. Previous reports identified two cases of NDUFA10 mutations related to LS development and complex I deficiency.
Researchers described the case of a 32-month-old boy with severe muscular weakness, poorly coordinated movement, and unable to stand and walk at initial evaluation. Magnetic resonance imaging scans showed the child had brain lesions, characterized by swelling and cell death. A global evaluation showed a moderate delay in development.
Over the next year, the boy showed a slight improvement in neurological development, but with intermittent relapses. These acute episodes usually were associated with febrile (non-specific) illness and with only partial recovery, so that a progressive neurologic decline was noted.
Test results and the boy’s profile suggested LS and a defect of energy production metabolism. A detailed biochemical and genetic analysis was subsequently performed to diagnose the disease and confirm the underling deficiency.
The researchers confirmed a deficiency in cell energy production, with insufficient complex I activity , and they assigned this to a mutation found in the NDUFA10 gene. This mutation has been reported previously.
Two different mutations in this gene also were described in a patient with LS. However, in contrast to that study, the current report showed the child had more moderate symptoms with later age of onset, longer survival, and no evidence of heart disease. This may suggest that NDUFA10 mutations can have different effects in brain and cardiac muscle.
“Our data suggest that even in patients apparently sharing the same genotype, the variability of single mutations may lead to different clinical, biochemical, and neuroradiologic phenotype,” the authors concluded.