MT-ND5

Variants (also called mutations) in the MT-ND5 gene have been identified a few people with Leigh syndrome. Children with this condition may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder. A few children with Leigh syndrome caused by MT-ND5 gene variants have had additional features that are not typical of Leigh syndrome, including slow growth before birth (intrauterine growth retardation) and distinctive facial features.

The MT-ND5 gene variants responsible for Leigh syndrome change single DNA building blocks (nucleotides) in the gene. These genetic changes disrupt the activity of complex I, impairing the ability of mitochondria to produce energy.  It is not known, however, how variants in the MT-ND5 gene are related to the specific features of Leigh syndrome.

Variants in the MT-ND5 gene are responsible for a small percentage of all cases of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). This condition affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy).  

The MT-ND5 gene variants that cause MELAS alter single nucleotides in the gene. Most people with MELAS caused by MT-ND5 gene variants have  the variant that replaces the nucleotide guanine with the nucleotide adenine at gene position 13513 (written as G13513A).  

Most commonly, MT-ND5 gene variants that cause MELAS have been shown to reduce the activity of complex I, which disrupts energy production within mitochondria. Although these abnormalities have the greatest impact on tissues that require a lot of energy (such as the brain and muscles), researchers have not determined how changes in the MT-ND5 gene lead to the specific signs and symptoms of MELAS.

Variants in the MT-ND5 gene also have been identified in patients with the major features of MELAS in combination with other mitochondrial diseases. For example, researchers have found MT-ND5 gene variants in several individuals with the signs of MELAS and some features of Leigh syndrome, a progressive brain disorder that typically appears in infancy or early childhood. In other cases, people with MELAS and a change in the MT-ND5 gene have developed sudden, progressive vision loss characteristic of an eye disease called Leber hereditary optic neuropathy.  A few individuals have been reported with signs and symptoms of all three of these mitochondrial conditions—MELAS, Leigh syndrome, and Leber hereditary optic neuropathy.

It is unclear why changes in the MT-ND5 gene can cause such a large variety of signs and symptoms. Even within a single family, affected individuals may have different health problems caused by the same genetic change.

MedlinePlus Genetics provides information about Mitochondrial complex I deficiency