Neuropathy, ataxia, and retinitis pigmentosa
Encyclopedia
Neuropathy, ataxia, and retinitis pigmentosa (NARP) is a condition that causes a variety of signs and symptoms chiefly affecting the nervous system
. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); 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.
Learning disabilities and developmental delays are often seen in children with NARP, and older individuals with this condition may experience a loss of intellectual function (dementia
). Other features of NARP include seizures, hearing loss, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). These signs and symptoms vary among affected individuals.
Neuropathy, ataxia, and retinitis pigmentosa is a condition related to changes in mitochondrial DNA
. Mutations in the MT-ATP6 gene cause neuropathy, ataxia, and retinitis pigmentosa. The MT-ATP6 gene provides instructions for making a protein that is essential for normal mitochondrial function. Through a series of chemical reactions, mitochondria use oxygen and simple sugars to create adenosine triphosphate
(ATP), the cell's main energy source. The MT-ATP6 protein forms one part (subunit) of an enzyme called ATP synthase
, which is responsible for the last step in ATP production. Mutations in the MT-ATP6 gene alter the structure or function of ATP synthase, reducing the ability of mitochondria to make ATP. It remains unclear how this disruption in mitochondrial energy production leads to muscle weakness, vision loss, and the other specific features of NARP.
This condition is inherited in a pattern reflecting its location in mitochondrial DNA, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. Most individuals with NARP have a specific MT-ATP6 mutation in 70 percent to 90 percent of their mitochondria. When this mutation is present in a higher percentage of a person's mitochondria—greater than 90 percent to 95 percent—it causes a more severe condition known as maternally inherited Leigh syndrome. Because these two conditions result from the same genetic changes and can occur in different members of a single family, researchers believe that they may represent a spectrum of overlapping features instead of two distinct syndromes.
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye (the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
). In some cases, the vision loss results from a condition called retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
. This eye disease causes the light-sensing cells of the retina gradually to deteriorate.
Learning disabilities and developmental delays are often seen in children with NARP, and older individuals with this condition may experience a loss of intellectual function (dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
). Other features of NARP include seizures, hearing loss, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). These signs and symptoms vary among affected individuals.
Neuropathy, ataxia, and retinitis pigmentosa is a condition related to changes in mitochondrial DNA
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
. Mutations in the MT-ATP6 gene cause neuropathy, ataxia, and retinitis pigmentosa. The MT-ATP6 gene provides instructions for making a protein that is essential for normal mitochondrial function. Through a series of chemical reactions, mitochondria use oxygen and simple sugars to create adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP), the cell's main energy source. The MT-ATP6 protein forms one part (subunit) of an enzyme called ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...
, which is responsible for the last step in ATP production. Mutations in the MT-ATP6 gene alter the structure or function of ATP synthase, reducing the ability of mitochondria to make ATP. It remains unclear how this disruption in mitochondrial energy production leads to muscle weakness, vision loss, and the other specific features of NARP.
This condition is inherited in a pattern reflecting its location in mitochondrial DNA, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. Most individuals with NARP have a specific MT-ATP6 mutation in 70 percent to 90 percent of their mitochondria. When this mutation is present in a higher percentage of a person's mitochondria—greater than 90 percent to 95 percent—it causes a more severe condition known as maternally inherited Leigh syndrome. Because these two conditions result from the same genetic changes and can occur in different members of a single family, researchers believe that they may represent a spectrum of overlapping features instead of two distinct syndromes.