Diseases Studied

Sensorineural hearing loss, or permanent hearing loss caused by irreversible damage to the inner ear or the nerve that transmits signals from the brain to the ear. Onset occurs a few days to weeks following exposure to aminoglycoside antibiotics. Specific genetic mutations in mitochondria (specialized cellular structures that produce energy) predispose individuals to ototoxicity (ear poisoning by certain medications).

A rare, X-linked (X chromosome genetic mutation), inherited disorder affecting primarily males with variable age of onset. It is characterized by heart dysfunction and low white blood cell counts. Endocardial fibroelastosis (buildup of connective tissues and elastin fibers) causes hypertrophic cardiomyopathy (increased heart muscle thickness). Symptoms and signs include irregular heartbeat, fatigue, muscle weakness, heart failure, shortness of breath, frequent infections, exercise intolerance, distinctive facial features, growth delay, and learning disability.

A rare disorder caused by inherited or acquired genetic mutations in mitochondria (specialized cell structures that produce energy). It is characterized by childhood or adult onset of progressive impairment of eye movements of typically affecting both eyes symmetrically. Manifestations include ptosis (eyelid drooping) and ophthalmoparesis or ophthalmoplegia (eye muscle weakness or paralysis). Other symptoms may include dysphagia (swallowing problems) and generalized limb muscle weakness.

An inherited, multisystemic, mitochondrial disorder characterized by protein complex I deficiency. Shortage of this protein complex (structure made up of multiple proteins) disrupts the first step in oxidative phosphorylation, the process by which mitochondria (specialized cell structures) produce most of the body's energy. Typical manifestations include Leigh syndrome (see below), encephalopathy (brain disease), ataxia (lack of coordination), involuntary movements, hypotonia (low muscle tone), muscle pain, weakness, seizures, exercise intolerance, fatigue, lactic acidosis (high blood lactate levels), optic nerve atrophy (wasting), and heart, kidney, or liver dysfunction.

An inherited, multisystemic, mitochondrial disorder characterized by protein complex II deficiency. Shortage of this protein complex (structure made up of multiple proteins) disrupts the second step of oxidative phosphorylation, the process by which mitochondria (specialized cell structures) produce energy which the body can use. Typical manifestations include Leigh syndrome (see below), leukodystrophy, which is the destruction of white matter made up of myelin (a fatty coating) around nerves in the brain, as well as seizures, psychomotor regression (loss of mental and motor skills), vision and hearing loss, speech problems, hypertonia (increased muscle tone), extremity muscle atrophy (wasting), hyperreflexia (exaggerated reflexes), cardiomyopathy (heart disease), and fatigue.

An inherited, multisystemic, mitochondrial disorder characterized by protein complex III deficiency. Defects of this protein complex (structure made up of multiple proteins) disrupts the third step of oxidative phosphorylation, the process by which mitochondria (specialized cell structures) produce most of the body's energy. Signs include encephalopathy (brain disease), hypoglycemia (low blood glucose levels), hypotonia (low muscle tone), weakness, seizures, lactic acidosis (high blood lactate levels), exercise intolerance, hearing and vision loss, seizures, cardiomyopathy (heart disease), and liver and kidney disease.

An inherited, multisystemic, mitochondrial disorder characterized by protein complex IV deficiency. Shortage of this protein complex (structure made up of multiple proteins) disrupts the fourth step of oxidative phosphorylation, the process by which mitochondria (specialized cell structures) produce most of the body's energy. Signs include Leigh syndrome (see below), encephalopathy (brain disease), lack of coordination, feeding difficulties, hypotonia (low muscle tone), muscle weakness, seizures, lactic acidosis (high blood lactate levels), intellectual disability, developmental regression (loss of acquired skills), heart disease, and kidney or liver problems.

An inherited, multisystemic, mitochondrial disorder characterized by protein complex V deficiency. Defects of this protein complex (structure made up of multiple proteins) disrupts the last step of oxidative phosphorylation, the process by which mitochondria (specialized cell structures) produce most of the body's energy. Signs include Leigh syndrome (see below), feeding difficulty, extreme fatigue, hypotonia (low muscle tone), developmental delay, lactic acidosis (high blood lactate levels), encephalopathy (brain disease), hypertrophic cardiomyopathy (heart muscle thickening), heart failure, ataxia (lack of coordination), weakness, vision loss, and nerve damage.

A rare, inherited disorder characterized by deficiency of a protein called coenzyme Q10, or ubiquinone. Age of onset varies. Manifestations include: encephalomyopathy (severe brain disease combined with muscle weakness), ataxia (lack of coordination), seizures, spasticity (muscle rigidity), nystagmus (abnormal eye movements), vision loss, intellectual disability, hypotonia (low muscle tone), dystonia (involuntary movements), hypertrophic cardiomyopathy (heart muscle thickening), and nephrotic syndrome (kidney damage causing protein excretion in the urine).

A rare, mitochondrial (referring to specialized cell structures that produce energy) disorder characterized by hearing loss, especially of high tones, and hyperglycemia (high blood glucose levels) due to diabetes mellitus. The disorder is caused by mutations in the DNA of mitochondria (specialized cell structures that produce energy). Because the mitochondrial DNA mutation is inherited from mothers, it is a maternally inherited disorder. Onset of hearing loss usually occurs before diabetes, typically in mid-adulthood.

A term indicating severe brain disease combined with muscle weakness. "Encephalo" pertains to the brain, while "myo" pertains to muscle. This disorder characterizes a group of mitochondrial disorders. When the genetic material within mitochondria (specialized cell structures that produce energy) is mutated, it results in disruption of the oxidative phosphorylation pathway through which the body produces energy. The brain is the organ most susceptible to mitochondrial dysfunction, causing neurological dysfunction such as cognitive impairment, seizures, and movement disorders.

A term indicating severe brain disease. "Encephalo" pertains to the brain. This disorder characterizes a group of mitochondrial disorders. When the genetic material within mitochondria (specialized cell structures that produce energy) is mutated, it results in disruption of the oxidative phosphorylation pathway through which the body produces energy. The brain is the organ most susceptible to mitochondrial dysfunction, causing neurological dysfunction such as cognitive impairment, seizures, and movement disorders.

A rare disorder characterized by degeneration of the brain tissue within the striatum, which is the largest component of the basal ganglia (regions of the brain that regulate movements). Symptoms and signs usually manifest in the first 2 years of life in the familial (inherited) form of this disorder, and include involuntary muscle and eye movements, developmental regression (loss of acquired skills), spasticity (muscle rigidity) and myoclonus (muscle rigidity and jerking, respectively), dysphagia (difficulty swallowing), intellectual deficits, ataxia (lack of coordination), and optic nerve atrophy.

A rare brain disorder that occurs in individuals along with advanced liver damage, such as severe hepatitis.

A rare disorder affecting nerves and muscles caused by genetic mutations affecting the mitochondria (specialized cell structures that produce energy). It is characterized by progressive loss of eye movement until complete paralysis (absence of movement), ptosis (eyelid drooping), and abnormal pigmentation of the membranous lining of the eyes. Other symptoms include cognitive deficits, ataxia (lack of coordination), mild skeletal muscle weakness, cardiac conduction block (defective electrical signaling in the heart), hearing loss, diabetes, and stunted growth. Most patients with this disease have a sporadic mutation in the DNA of the mitochondria (specialized cell structures that produce energy).

A rare, inherited disorder caused by genetic mutations in DNA of the mitochondria (specialized cell structures that produce energy). Because the mitochondrial DNA mutation is inherited from mothers, it is a maternally inherited disorder. This results in degeneration of the optic nerve that sends messages from the eyes to the brain, leading to progressive central vision loss in both eyes. Symptoms usually manifest in adolescence or adulthood, including loss of both color vision and visual acuity (sharpness). Male individuals are affected more frequently than females. The heart may show an extra electrical pathway between the atria (upper chambers) and ventricles (lower chambers).

A rare, inherited disorder that combines central vision loss in both eyes with other neurological and/or systemic abnormalities. Genetic mutations in the DNA of mitochondria (specialized cell structures that produce energy) result in degeneration of the optic nerve that sends messages from the eyes to the brain. Symptoms include blurry or cloudy vision, loss of both color vision and acuity (sharpness), poor coordination, numbness, tremors, movement disorders, irregular heartbeats, spasticity (muscle rigidity), spinal cord lesions, and generalized muscle weakness.

A rare disorder characterized by severe brain damage in the basal ganglia (regions of the brain that regulate movements), brain stem (region of the lower brain that sends signals to and from the body) or both. Eighty percent of mutations occur in the genetic material in cell nuclei, while 20% occur in DNA within mitochondria (specialized cell structures that produce energy). Symptoms and signs manifest in infancy, including psychomotor regression (loss of mental and motor skills), dysphagia (difficulty swallowing), feeding and growth problems, seizures, hypotonia (low muscle tone), diarrhea, vomiting, involuntary muscle movements, ataxia (lack of coordination), peripheral neuropathy (sensory loss and muscle weakness of the extremities), lactic acidosis (high blood lactate levels), hypertrophic cardiomyopathy (heart muscle thickening), and respiratory failure.

A term referring to disorders characterized by loss of white matter in the brain. White matter is comprised of nerves surrounded by myelin (a fatty, white, insulation). Loss of white matter results in cognitive impairments, sensory loss, and muscle weakness throughout the body. This occurs commonly in some disorders of mitochondria (specialized cell structures that produce energy) when the oxidative phosphorylation pathway, or the process that produces energy, is disrupted.

A rare disorder caused by genetic mutations in the DNA of mitochondria (specialized cell structures that produce energy) which leads to severe brain damage. Mitochondrial DNA can only be passed along from mothers, making this disorder "maternally inherited." Symptoms manifest in infancy, including psychomotor regression (loss of mental and motor skills), dysphagia (difficulty swallowing), feeding and growth problems, hypotonia (low muscle tone), diarrhea, vomiting, involuntary muscle movements, ataxia (lack of coordination), peripheral neuropathy (sensory loss and muscle weakness in the extremities), lactic acidosis (high blood lactate levels), hypertrophic cardiomyopathy (heart muscle thickening), and respiratory failure.

A rare, inherited disorder of the nerves and muscles, caused by mutations in the mitochondria (specialized cell structures that produce energy). Symptoms include encephalopathy (brain disease), lactic acidosis (high blood lactate levels), stroke-like episodes involving temporary hemiparesis (muscle weakness on one side of the body), seizures, vision and hearing loss, severe recurrent headaches, altered consciousness, intellectual disability, muscle, and abdominal pain, loss of appetite, vomiting, fatigue, myoclonus (muscle twitches), ataxia (lack of coordination), diabetes, hormonal imbalance, and heart and kidney problems.

A rare, multisystemic disorder affecting the nervous system and muscles. Symptoms include myoclonus (muscle twitches), muscle weakness, seizures, spasticity (muscle rigidity), ataxia (lack of coordination), peripheral neuropathy (sensory changes and muscle weakness in the extremities), intellectual deficits, optic nerve atrophy (wasting), short stature, cardiomyopathy (heart disease), and, less commonly, lipomas (fatty tumors under the skin). Muscle cells from affected individuals reveal abnormal "ragged-red" muscle fibers when viewed under a microscope.

Chronic, often inherited, multisystemic, genetic disorders involving dysfunction of the mitochondria (specialized cell structures that produce energy). These disorders affect 1 in every 5,000 people. Due to insufficient energy, the body's tissues and organs become dysfunctional. Symptoms and signs manifest primarily in the brain, eyes, ears, nerves, muscles, kidneys, liver, and/or heart. Severe cases may lead to failure of one or more organs.

A term characterizing a group of inherited disorders in which copies of the DNA (genetic material) within mitochondria (specialized cell structures that produce energy) are severely reduced in number. This results in impaired energy production required for proper functioning of the body tissues and organs. These disorders primarily affect the brain, liver, digestive system, nerves, and skeletal muscles.

A rare, inherited disorder characterized by progressive digestive and nervous system impairment. Digestive symptoms include gastrointestinal dysmotility (impaired movement of food through the digestive tract), early satiety (feeling full), dysphagia (difficulty swallowing), nausea, vomiting, diarrhea, intestinal blockages, abdominal pain, extreme weight loss, and cachexia (loss of muscle mass). Neurological manifestations include leukoencephalopathy, which is the degeneration of white matter comprised of myelin (a fatty coating) surrounding nerve fibers in the brain, ptosis (eyelid drooping), eye muscle weakness, peripheral neuropathy (sensory changes and muscle weakness in the extremities), and hearing loss.

A term referring to more than one piece of DNA (genetic material) that is missing within the mitochondria (specialized cell structures that produce energy). These DNA pieces may differ in size. Disorders caused by the missing mitochondrial DNA are often inherited due to mutations in nuclear DNA (genetic material found in the nucleus of cells) which are responsible for repairing, building, or maintaining mitochondrial DNA. These disease affects the muscles, nerves, eyes, and heart and often present as chronic progressive external ophthalmoplegia (see above).

In contrast to "isolated" or singularly occurring enzyme deficiencies, this is a term indicating a disruption of more than one step in the oxidative phosphorylation pathway (the process of energy production in the cells of the body). Multiple mutations, occurring particularly in mitochondria (specialized cell structures that conduct oxidative phosphorylation), cause deficiencies (shortages) or complete absence of certain enzymes (proteins that break down specific substances within the body). These enzymes are required for proper completion of each of the steps of the energy production pathway, also known as oxidative phosphorylation.

A rare, inherited disorder caused by genetic mutations in mitochondria (specialized cell structures that produce energy). It is characterized by neuropathy, which results in muscle weakness and abnormal sensations such as tingling, numbness, or pain in the limbs; ataxia (lack of coordination and balance); and retinitis pigmentosa (deterioration of the retina, or light-sensitive tissues lining the back of the eye), leading to vision loss. Other symptoms may include hearing loss, seizures, intellectual disability, and electrical abnormalities of the heart.

A rare disorder usually caused by mutations of DNA in mitochondria (specialized cell structures that produce energy) that arise during embryonic development. Symptoms manifest in infancy, including low red and white blood cells, low platelet levels, fatigue, pallor (paleness), weakness, frequent infections, easy bleeding and bruising, abnormalities of blood and bone marrow cells when viewed under a microscope, scarring of the pancreas, liver steatosis (fatty liver), liver failure, diabetes, malabsorption, lactic acidosis (high blood lactate levels), ptosis (eyelid drooping), vision and hearing loss, seizures, and movement disorders.

A rare disorder with varying inheritance patterns characterized by deficiency of the enzyme that breaks down pyruvate in the first step of the Krebs cycle. The Krebs cycle is required to release energy stored in carbohydrates, fats, and proteins. Due to this energy disruption, elevations of pyruvate and lactic acid occur and cause psychomotor regression or delay (impairments in mental and motor skills), cognitive impairments, difficulty walking, poor coordination, hypotonia (low muscle tone), seizures, structural brain abnormalities, breathing problems, irregular heartbeat, nausea, and vomiting.

A rare, inherited disorder caused by depletion (fewer) or deletions (fragmented) DNA within mitochondria (specialized cell structures that produce energy) in skeletal muscles and limb nerves. It is characterized by abnormal sensations such as tingling, numbness, or pain in the arms and legs, ataxia (lack of coordination), generalized muscle weakness, seizures, ptosis (eyelid drooping), ophthalmoplegia (eye muscle weakness), dysarthria (speech impairment due to muscle weakness), vision loss, migraines, liver disease, cognitive impairment, depression, and myoclonus (muscle twitches).