Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1

• Five patients with isolated complex I deficiency and NDUFS1 or NDUFV1 mutations are presented.
• A literature review identified an additional 45 patients with NDUFS1 or NDUFV1 mutations.
• Commonly reported clinical and imaging findings of all 50 patients are presented.
• Patients with NDUFS1 mutations tend to have earlier onset and shorter life span.
• The results add knowledge to genotype–phenotype correlations in mitochondrial diseases.

We report clinical, metabolic, genetic and neuroradiological findings in five patients from three different families with isolated complex I deficiency. Genetic analysis revealed mutations in NDUFS1 in three patients and in NDUFV1 in two patients. Four of the mutations are novel and affect amino acid residues that either are invariant among species or conserved in their properties. The presented clinical courses are characterized by leukoencephalopathy or early death and expand the already heterogeneous phenotypic spectrum. A literature review was performed, showing that patients with mutations in NDUFS1 in general have a worse prognosis than patients with mutations in NDUFV1.