Mitochondrial complex I deficiency affects how the cell makes energy in a part of the cell called the mitochondria, which is vital for the cell’s work.
Mitochondrial complex I deficiency can vary in severity, from a very serious condition that can be fatal in newborns to disorders that show up later in life. People with this deficiency can have different symptoms like brain problems, heart issues, muscle weakness, liver troubles, vision loss, or even Parkinson’s disease. Some individuals with mitochondrial complex I deficiency also have a condition called Leigh syndrome. Leigh syndrome is a progressive problem that affects the central nervous system, and it causes issues like intellectual disability, muscle weakness, trouble breathing, vision and hearing problems, and heart disease. Unfortunately, Leigh syndrome often gets worse over time, and many people with it don’t live past their first two years. Right now, there isn’t a cure for mitochondrial complex I deficiency. Treatment focuses on managing individual symptoms, but it can’t fix the main cause of the problem.
There are many genes that can cause mitochondrial complex I deficiency and the test we use looks for pathogenic (disease-causing) variants in the NDUFAF5, NDUFS4, and NDUFS6 genes, all of which exhibit autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 290 chance to be a carriers in the NDUFAF5 and NDUF6 genes.
Other names for this condition are NADH-coenzyme Q reductase deficiency and NADH:Q(1) oxidoreductase deficiency.
Resources:
United Mitochondrial Disease Foundation
Revised November 2023
