bowang0911/MedQuAD huggingface dataset:
Progressive external ophthalmoplegia is a condition caused by defects in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA or mtDNA.  Progressive external ophthalmoplegia can result from mutations in several different genes. In some cases, mutations in the MT-TL1 gene, which is located in mtDNA, cause progressive external ophthalmoplegia. In other cases, mutations in nuclear DNA are responsible for the condition, particularly mutations in the POLG, SLC25A4, and C10orf2 genes. These genes are critical for mtDNA maintenance. Although the mechanism is unclear, mutations in any of these three genes lead to large deletions of mtDNA, ranging from 2,000 to 10,000 DNA building blocks (nucleotides).  Researchers have not determined how deletions of mtDNA lead to the specific signs and symptoms of progressive external ophthalmoplegia, although the features of the condition are probably related to impaired oxidative phosphorylation. It has been suggested that eye muscles are commonly affected by mitochondrial defects because they are especially dependent on oxidative phosphorylation for energy.
Progressive external ophthalmoplegia can have different inheritance patterns depending on the gene involved.  When this condition is caused by mutations in the MT-TL1 gene, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.  When the nuclear genes POLG, SLC25A4, or C10orf2 are involved, progressive external ophthalmoplegia is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Certain mutations in the POLG gene can also cause a form of the condition that is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Some mutations in the POLG gene that cause progressive external ophthalmoplegia occur during a person's lifetime and are not inherited. These genetic changes are called somatic mutations.
These resources address the diagnosis or management of progressive external ophthalmoplegia:  - Gene Review: Gene Review: Mitochondrial DNA Deletion Syndromes  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1  - Genetic Testing Registry: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 2  - Genetic Testing Registry: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3  - Genetic Testing Registry: Progressive external ophthalmoplegia  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a disorder affecting the development of the lungs and their blood vessels. The disorder affects the millions of small air sacs (alveoli) in the lungs and the tiny blood vessels (capillaries) in the alveoli. It is through these alveolar capillaries that inhaled oxygen enters the bloodstream for distribution throughout the body and carbon dioxide leaves the bloodstream to be exhaled.  In ACD/MPV, the alveolar capillaries fail to develop normally. The number of capillaries is drastically reduced, and existing capillaries are improperly positioned within the walls of the alveoli. These abnormalities in capillary number and location impede the exchange of oxygen and carbon dioxide.  Other abnormalities of the blood vessels in the lungs also occur in ACD/MPV. The veins that carry blood from the lungs into the heart (pulmonary veins) are improperly positioned and may be abnormally bundled together with arteries that carry blood from the heart to the lungs (pulmonary arteries). The muscle tissue in the walls of the pulmonary arteries may be overgrown, resulting in thicker artery walls and a narrower channel. These changes restrict normal blood flow, which causes high blood pressure in the pulmonary arteries (pulmonary hypertension) and requires the heart to pump harder.  Most infants with ACD/MPV are born with additional abnormalities. These may include abnormal twisting (malrotation) of the large intestine or other malformations of the gastrointestinal tract. Cardiovascular and genitourinary abnormalities are also common in affected individuals.  Infants with ACD/MPV typically develop respiratory distress within a few minutes to a few hours after birth. They experience shortness of breath and cyanosis, which is a bluish appearance of the skin, mucous membranes, or the area underneath the fingernails caused by a lack of oxygen in the blood. Without lung transplantation, infants with ACD/MPV have not been known to survive past one year of age, and most affected infants live only a few weeks.
ACD/MPV can be caused by mutations in the FOXF1 gene. The protein produced from the FOXF1 gene is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of many other genes. The FOXF1 protein is important in development of the lungs and their blood vessels. The FOXF1 protein is also involved in the development of the gastrointestinal tract. Mutations in the FOXF1 gene that cause ACD/MPV result in an inactive protein that cannot regulate development, leading to abnormal formation of the pulmonary blood vessels and gastrointestinal tract.  ACD/MPV can also be caused by a deletion of genetic material on the long arm of chromosome 16 in a region known as 16q24.1. This region includes several genes, including the FOXF1 gene. Deletion of one copy of the FOXF1 gene in each cell reduces the production of the FOXF1 protein. A shortage of FOXF1 protein affects the development of pulmonary blood vessels and causes the main features of ACD/MPV. Researchers suggest that the loss of other genes in this region probably causes the additional abnormalities, such as heart defects, seen in some infants with this disorder. Like FOXF1, these genes also provide instructions for making transcription factors that regulate development of various body systems before birth.  In about 60 percent of affected infants, the genetic cause of ACD/MPV is unknown.
ACD/MPV is usually not inherited, and most affected people have no history of the disorder in their family. The genetic changes associated with this condition usually occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. When the condition is caused by a FOXF1 gene mutation or deletion, one altered or missing gene in each cell is sufficient to cause the disorder. Individuals with ACD/MPV do not pass the genetic change on to their children because they do not live long enough to reproduce.  A few families have been identified in which more than one sibling has ACD/MPV. It is not clear how ACD/MPV is inherited in these families because no genetic changes have been identified.
These resources address the diagnosis or management of ACD/MPV:  - Genetic Testing Registry: Alveolar capillary dysplasia with misalignment of pulmonary veins  - MedlinePlus Encyclopedia: Alveolar Abnormalities   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Diastrophic dysplasia is a disorder of cartilage and bone development. Affected individuals have short stature with very short arms and legs. Most also have early-onset joint pain (osteoarthritis) and joint deformities called contractures, which restrict movement. These joint problems often make it difficult to walk and tend to worsen with age. Additional features of diastrophic dysplasia include an inward- and upward-turning foot (clubfoot), progressive abnormal curvature of the spine, and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth (a cleft palate). Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.  The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis type 2; however, diastrophic dysplasia tends to be less severe. Although some affected infants have breathing problems, most people with diastrophic dysplasia live into adulthood.
Diastrophic dysplasia is one of several skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.
Primary carnitine deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy.  Signs and symptoms of primary carnitine deficiency typically appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), a weakened and enlarged heart (cardiomyopathy), confusion, vomiting, muscle weakness, and low blood sugar (hypoglycemia). The severity of this condition varies among affected individuals. Some people with primary carnitine deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. All individuals with this disorder are at risk for heart failure, liver problems, coma, and sudden death.  Problems related to primary carnitine deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
Mutations in the SLC22A5 gene cause primary carnitine deficiency. This gene provides instructions for making a protein called OCTN2 that transports carnitine into cells. Cells need carnitine to bring certain types of fats (fatty acids) into mitochondria, which are the energy-producing centers within cells. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the SLC22A5 gene result in an absent or dysfunctional OCTN2 protein. As a result, there is a shortage (deficiency) of carnitine within cells. Without carnitine, fatty acids cannot enter mitochondria and be used to make energy. Reduced energy production can lead to some of the features of primary carnitine deficiency, such as muscle weakness and hypoglycemia. Fatty acids may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of the disorder.
These resources address the diagnosis or management of primary carnitine deficiency:  - Baby's First Test  - Gene Review: Gene Review: Systemic Primary Carnitine Deficiency  - Genetic Testing Registry: Renal carnitine transport defect  - The Linus Pauling Institute: L-Carnitine   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Multiple sulfatase deficiency is a condition that mainly affects the brain, skin, and skeleton. Because the signs and symptoms of multiple sulfatase deficiency vary widely, researchers have split the condition into three types: neonatal, late-infantile, and juvenile.  The neonatal type is the most severe form, with signs and symptoms appearing soon after birth. Affected individuals have deterioration of tissue in the nervous system (leukodystrophy), which can contribute to movement problems, seizures, developmental delay, and slow growth. They also have dry, scaly skin (ichthyosis) and excess hair growth (hypertrichosis). Skeletal abnormalities can include abnormal side-to-side curvature of the spine (scoliosis), joint stiffness, and dysostosis multiplex, which refers to a specific pattern of skeletal abnormalities seen on x-ray. Individuals with the neonatal type typically have facial features that can be described as "coarse." Affected individuals may also have hearing loss, heart malformations, and an enlarged liver and spleen (hepatosplenomegaly). Many of the signs and symptoms of neonatal multiple sulfatase deficiency worsen over time.  The late-infantile type is the most common form of multiple sulfatase deficiency. It is characterized by normal cognitive development in early childhood followed by a progressive loss of mental abilities and movement (psychomotor regression) due to leukodystrophy or other brain abnormalities. Individuals with this form of the condition do not have as many features as those with the neonatal type, but they often have ichthyosis, skeletal abnormalities, and coarse facial features.  The juvenile type is the rarest form of multiple sulfatase deficiency. Signs and symptoms of the juvenile type appear in mid- to late childhood. Affected individuals have normal early cognitive development but then experience psychomotor regression; however, the regression in the juvenile type usually occurs at a slower rate than in the late-infantile type. Ichthyosis is also common in the juvenile type of multiple sulfatase deficiency.  Life expectancy is shortened in individuals with all types of multiple sulfatase deficiency. Typically, affected individuals survive only a few years after the signs and symptoms of the condition appear, but life expectancy varies depending on the severity of the condition and how quickly the neurological problems worsen.
Multiple sulfatase deficiency is caused by mutations in the SUMF1 gene. This gene provides instructions for making an enzyme called formylglycine-generating enzyme (FGE). This enzyme is found in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. The FGE enzyme modifies other enzymes called sulfatases, which aid in breaking down substances that contain chemical groups known as sulfates. These substances include a variety of sugars, fats, and hormones.  Most SUMF1 gene mutations severely reduce the function of the FGE enzyme or lead to the production of an unstable enzyme that is quickly broken down. The activity of multiple sulfatases is impaired because the FGE enzyme modifies all known sulfatase enzymes. Sulfate-containing molecules that are not broken down build up in cells, often resulting in cell death. The death of cells in particular tissues, specifically the brain, skeleton, and skin, cause many of the signs and symptoms of multiple sulfatase deficiency.  Research indicates that mutations that lead to reduced FGE enzyme function are associated with the less severe cases of the condition, whereas mutations that lead to the production of an unstable FGE enzyme tend to be associated with the more severe cases of multiple sulfatase deficiency.
Inclusion body myopathy 2 is a condition that primarily affects skeletal muscles, which are muscles that the body uses for movement. This disorder causes muscle weakness that appears in late adolescence or early adulthood and worsens over time.  The first sign of inclusion body myopathy 2 is weakness of a muscle in the lower leg called the tibialis anterior. This muscle helps control up-and-down movement of the foot. Weakness in the tibialis anterior alters the way a person walks and makes it difficult to run and climb stairs. As the disorder progresses, weakness also develops in muscles of the upper legs, hips, shoulders, and hands. Unlike most forms of myopathy, inclusion body myopathy 2 usually does not affect the quadriceps, which are a group of large muscles at the front of the thigh. This condition also does not affect muscles of the eye or heart, and it does not cause neurological problems. Weakness in leg muscles makes walking increasingly difficult, and most people with inclusion body myopathy 2 require wheelchair assistance within 20 years after signs and symptoms appear.  People with the characteristic features of inclusion body myopathy 2 have been described in several different populations. When the condition was first reported in Japanese families, researchers called it distal myopathy with rimmed vacuoles (DMRV) or Nonaka myopathy. When a similar disorder was discovered in Iranian Jewish families, researchers called it rimmed vacuole myopathy or hereditary inclusion body myopathy (HIBM). It has since become clear that these conditions are variations of a single disorder caused by mutations in the same gene.
Mutations in the GNE gene cause inclusion body myopathy 2. The GNE gene provides instructions for making an enzyme found in cells and tissues throughout the body. This enzyme is involved in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions including cell movement (migration), attaching cells to one another (adhesion), signaling between cells, and inflammation.  The mutations responsible for inclusion body myopathy 2 reduce the activity of the enzyme produced from the GNE gene, which decreases the production of sialic acid. As a result, less of this simple sugar is available to attach to cell surface molecules. Researchers are working to determine how a shortage of sialic acid leads to progressive muscle weakness in people with inclusion body myopathy 2. Sialic acid is important for the normal function of many different cells and tissues, so it is unclear why the signs and symptoms of this disorder appear to be limited to the skeletal muscles.
These resources address the diagnosis or management of inclusion body myopathy 2:  - Gene Review: Gene Review: GNE-Related Myopathy  - Genetic Testing Registry: Inclusion body myopathy 2  - Genetic Testing Registry: Nonaka myopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Lactate dehydrogenase deficiency is a condition that affects how the body breaks down sugar to use as energy in cells, primarily muscle cells.  There are two types of this condition: lactate dehydrogenase-A deficiency (sometimes called glycogen storage disease XI) and lactate dehydrogenase-B deficiency.  People with lactate dehydrogenase-A deficiency experience fatigue, muscle pain, and cramps during exercise (exercise intolerance). In some people with lactate dehydrogenase-A deficiency, high-intensity exercise or other strenuous activity leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure. Some people with lactate dehydrogenase-A deficiency develop skin rashes. The severity of the signs and symptoms among individuals with lactate dehydrogenase-A deficiency varies greatly.  People with lactate dehydrogenase-B deficiency typically do not have any signs or symptoms of the condition. They do not have difficulty with physical activity or any specific physical features related to the condition. Affected individuals are usually discovered only when routine blood tests reveal reduced lactate dehydrogenase activity.
Mutations in the LDHA gene cause lactate dehydrogenase-A deficiency, and mutations in the LDHB gene cause lactate dehydrogenase-B deficiency. These genes provide instructions for making the lactate dehydrogenase-A and lactate dehydrogenase-B pieces (subunits) of the lactate dehydrogenase enzyme. This enzyme is found throughout the body and is important for creating energy for cells. There are five different forms of this enzyme, each made up of four protein subunits. Various combinations of the lactate dehydrogenase-A and lactate dehydrogenase-B subunits make up the different forms of the enzyme.  The version of lactate dehydrogenase made of four lactate dehydrogenase-A subunits is found primarily in skeletal muscles, which are muscles used for movement. Skeletal muscles need large amounts of energy during high-intensity physical activity when the body's oxygen intake is not sufficient for the amount of energy required (anaerobic exercise). During anaerobic exercise, the lactate dehydrogenase enzyme is involved in the breakdown of sugar stored in the muscles (in the form of glycogen) to create additional energy. During the final stage of glycogen breakdown, lactate dehydrogenase converts a molecule called pyruvate to a similar molecule called lactate.  Mutations in the LDHA gene result in the production of an abnormal lactate dehydrogenase-A subunit that cannot attach (bind) to other subunits to form the lactate dehydrogenase enzyme. A lack of functional subunit reduces the amount of enzyme that is formed, mostly affecting skeletal muscles. As a result, glycogen is not broken down efficiently, leading to decreased energy in muscle cells. When muscle cells do not get sufficient energy during exercise or strenuous activity, the muscles become weak and muscle tissue can break down, as experienced by people with lactate dehydrogenase-A deficiency.  The version of lactate dehydrogenase made of four lactate dehydrogenase-B subunits is found primarily in heart (cardiac) muscle. In cardiac muscle, lactate dehydrogenase converts lactate to pyruvate, which can participate in other chemical reactions to create energy. LDHB gene mutations lead to the production of an abnormal lactate dehydrogenase-B subunit that cannot form the lactate dehydrogenase enzyme. Even though lactate dehydrogenase activity is decreased in the cardiac muscle of people with lactate dehydrogenase-B deficiency, they do not appear to have any signs or symptoms related to their condition. It is unclear why this type of enzyme deficiency does not cause any health problems.