Background: NDUFV1 gene mutations disrupt mitochondrial complex I and lead to neuro-regression with leukoencephalopathy and basal ganglia involvement on neuroimaging.

Objective: To provide a concise review on NDUFV1 related disorders while adding the largest cohort from a single center to the existing literature.

Materials and Methods: We retrospectively collected genetically proven cases of NDUFV1 mutations from our center over the last decade and explored reported instances in existing literature. We compiled and analysed clinical, radiological, and genetic data from both sources, conducting descriptive and comparative analyses. Factors influencing outcomes and radio-clinical phenotypes were examined. Three MRI patterns were identified: Leigh type, mitochondrial leukodystrophy (ML) type, and mixed type.

Results: The analysis involved 44 children (our centre: 7, literature: 37). Primary comorbidities included hypertonia with regression, ocular abnormalities, feeding issues, and onset hypotonia. Those with the Leigh-type MRI pattern exhibited elevated rates of breathing difficulties, while the mixed phenotype showed a higher prevalence of dystonia. The c.1156C>T variant in NDUFV1's exon 8, prevalent in Asians, is associated with irritability and dystonia, with seizures and Leigh MRI pattern less common. Mortality rates were higher in children with the Leigh-type MRI pattern and those not receiving the mitochondrial cocktail.

Conclusion: Mutation in the NDUFV1 gene results in neuro-regression, characterized by distinct radiological patterns on MRI Brain. MRI phenotyping might help predict outcome. Appropriate and timely treatment with mitochondrial cocktail may reduce the probability of death and may positively impact the long-term outcomes, regardless of the type of genetic variant or age of onset.

Aakash Mahesan
All India Institute of Medical Sciences
India

Puneet Choudhary
All India Institute of Medical Sciences
India

Gautam Kamila
All India Institute of Medical Sciences
India

Aradhana Rohil
All India Institute of Medical Sciences
India

Ankit Kumar Meena
All India Institute of Medical Sciences
India

Atin Kumar
All India Institute of Medical Sciences
India

Prashant Jauhari
All India Institute of Medical Sciences
India

Biswaroop Chakrabarty
All India Institute of Medical Sciences
India

Sheffali Gulati
All India Institute of Medical Sciences
India