mtDNAassociated Leigh syndrome affects the brain of afflicte

mtDNA-associated Leigh syndrome affects the brain of afflicted individuals and has an infantile onset. NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) has less severe symptoms with an onset in childhood. The same mtDNA mutation can cause both of these diseases. How can these differences in disease presentation, severity, and age of onset be explained for these two diseases?

Solution

Leigh syndrome is the result of mutations in both Nuclear or mitochondrial DNA, where as NARP solely due to the mutations in only mitochondrial DNA. This is the reason for differences in disease presentations in terms of severity and age of onset.

Leigh syndrome is a neurological disorder that usually apparent in the first year of life. This condition is characterized by progressive loss of psycho-motor or mental and movement abilities and respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly. The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia), which disrupts eating. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). A medical procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain. These regions include the basal ganglia (control movement), the cerebellum (controls the ability to balance and coordinates movement), brainstem (which connects the brain to the spinal cord and controls functions such as swallowing and breathing). Most people with Leigh syndrome have a mutation in nuclear DNA, about 20 percent have a mutation in mtDNA. Most genes associated with Leigh syndrome are involved in the process of energy production in mitochondria. Disruption of complex I, also called NADH:ubiquinone oxidoreductase, is the most common cause of Leigh syndrome, accounting for nearly one third of cases of the condition. At least 25 genes involved in the formation of complex I, found in either nuclear or mitochondrial DNA, have been associated with Leigh syndrome.

NARP: Neuropathy, ataxia, and retinitis pigmentosa (NARP) is causes a variety of signs and symptoms, primerly affecting the nervous system. In childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs, muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye (the retina). In some cases, the vision loss results from a condition called retinitis pigmentosa. This eye disease causes the light-sensing cells of the retina gradually to deteriorate. NARP results from mutations in the MT-ATP6 gene. This gene is present on mitochondrial DNA, also known as mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA.