bowang0911/MedQuAD huggingface dataset:
Mutations in the PANK2 gene cause pantothenate kinase-associated neurodegeneration.  The PANK2 gene provides instructions for making an enzyme called pantothenate kinase 2. This enzyme is active in mitochondria, the energy-producing centers within cells, where it plays a critical role in the formation of a molecule called coenzyme A. Found in all living cells, coenzyme A is essential for the body's production of energy from carbohydrates, fats, and some protein building blocks (amino acids).  Mutations in the PANK2 gene likely result in the production of an abnormal version of pantothenate kinase 2 or prevent cells from making any of this enzyme. A lack of functional pantothenate kinase 2 disrupts the production of coenzyme A and allows potentially harmful compounds to build up in the brain. This buildup leads to swelling and tissue damage, and allows iron to accumulate abnormally in certain parts of the brain. Researchers have not determined how these changes result in the specific features of pantothenate kinase-associated neurodegeneration. Because pantothenate kinase 2 functions in mitochondria, the signs and symptoms of this condition may be related to impaired energy production.
These resources address the diagnosis or management of pantothenate kinase-associated neurodegeneration:  - Gene Review: Gene Review: Pantothenate Kinase-Associated Neurodegeneration  - Genetic Testing Registry: Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration  - MedlinePlus Encyclopedia: Hallervorden-Spatz Disease  - MedlinePlus Encyclopedia: MRI   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
Xeroderma pigmentosum, which is commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun. Some affected individuals also have problems involving the nervous system.  The signs of xeroderma pigmentosum usually appear in infancy or early childhood. Many affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. Other affected children do not get sunburned with minimal sun exposure, but instead tan normally. By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name, xeroderma pigmentosum.  People with xeroderma pigmentosum have a greatly increased risk of developing skin cancer. Without sun protection, about half of children with this condition develop their first skin cancer by age 10. Most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on the face, lips, and eyelids. Cancer can also develop on the scalp, in the eyes, and on the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of other types of cancer, including brain tumors. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer.  The eyes of people with xeroderma pigmentosum may be painfully sensitive to UV rays from the sun. If the eyes are not protected from the sun, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of eye cancer, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.  About 30 percent of people with xeroderma pigmentosum develop progressive neurological abnormalities in addition to problems involving the skin and eyes. These abnormalities can include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. When these neurological problems occur, they tend to worsen with time.  Researchers have identified at least eight inherited forms of xeroderma pigmentosum: complementation group A (XP-A) through complementation group G (XP-G) plus a variant type (XP-V). The types are distinguished by their genetic cause. All of the types increase skin cancer risk, although some are more likely than others to be associated with neurological abnormalities.
Xeroderma pigmentosum is caused by mutations in genes that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals such as those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it causes problems. However, in people with xeroderma pigmentosum, DNA damage is not repaired normally. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die.  Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process known as nucleotide excision repair (NER). The proteins produced from these genes play a variety of roles in this process. They recognize DNA damage, unwind regions of DNA where the damage has occurred, snip out (excise) the abnormal sections, and replace the damaged areas with the correct DNA. Inherited abnormalities in the NER-related genes prevent cells from carrying out one or more of these steps. The POLH gene also plays a role in protecting cells from UV-induced DNA damage, although it is not involved in NER; mutations in this gene cause the variant type of xeroderma pigmentosum.  The major features of xeroderma pigmentosum result from a buildup of unrepaired DNA damage. When UV rays damage genes that control cell growth and division, cells can either die or grow too fast and in an uncontrolled way. Unregulated cell growth can lead to the development of cancerous tumors. Neurological abnormalities are also thought to result from an accumulation of DNA damage, although the brain is not exposed to UV rays. Researchers suspect that other factors damage DNA in nerve cells. It is unclear why some people with xeroderma pigmentosum develop neurological abnormalities and others do not.  Inherited mutations in at least eight genes have been found to cause xeroderma pigmentosum. More than half of all cases in the United States result from mutations in the XPC, ERCC2, or POLH genes. Mutations in the other genes generally account for a smaller percentage of cases.
These resources address the diagnosis or management of xeroderma pigmentosum:  - American Cancer Society: How are Squamous and Basal Cell Skin Cancer Diagnosed?  - American Cancer Society: How is Melanoma Diagnosed?  - Gene Review: Gene Review: Xeroderma Pigmentosum  - Genetic Testing Registry: Xeroderma pigmentosum  - Genetic Testing Registry: Xeroderma pigmentosum, complementation group b  - Genetic Testing Registry: Xeroderma pigmentosum, group C  - Genetic Testing Registry: Xeroderma pigmentosum, group D  - Genetic Testing Registry: Xeroderma pigmentosum, group E  - Genetic Testing Registry: Xeroderma pigmentosum, group F  - Genetic Testing Registry: Xeroderma pigmentosum, group G  - Genetic Testing Registry: Xeroderma pigmentosum, type 1  - Genetic Testing Registry: Xeroderma pigmentosum, variant type  - MedlinePlus Encyclopedia: Xeroderma Pigmentosum  - National Cancer Institute: Melanoma Treatment  - National Cancer Institute: Skin Cancer Treatment  - Xeroderma Pigmentosum Society, Inc.: Beta Carotene  - Xeroderma Pigmentosum Society, Inc.: Ultraviolet Radiation and Protection   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
Transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of a protein called amyloid (amyloidosis) in the body's organs and tissues. These protein deposits most frequently occur in the peripheral nervous system, which is made up of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Protein deposits in these nerves result in a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system, which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by amyloidosis. In some cases, the brain and spinal cord (central nervous system) are affected. Other areas of amyloidosis include the heart, kidneys, eyes, and gastrointestinal tract. The age at which symptoms begin to develop varies widely among individuals with this condition, and is typically between ages 20 and 70.  There are three major forms of transthyretin amyloidosis, which are distinguished by their symptoms and the body systems they affect.  The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. Impairments in bodily functions can include sexual impotence, diarrhea, constipation, problems with urination, and a sharp drop in blood pressure upon standing (orthostatic hypotension). Some people experience heart and kidney problems as well. Various eye problems may occur, such as cloudiness of the clear gel that fills the eyeball (vitreous opacity), dry eyes, increased pressure in the eyes (glaucoma), or pupils with an irregular or "scalloped" appearance. Some people with this form of transthyretin amyloidosis develop carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers.  The leptomeningeal form of transthyretin amyloidosis primarily affects the central nervous system. In people with this form, amyloidosis occurs in the leptomeninges, which are two thin layers of tissue that cover the brain and spinal cord. A buildup of protein in this tissue can cause stroke and bleeding in the brain, an accumulation of fluid in the brain (hydrocephalus), difficulty coordinating movements (ataxia), muscle stiffness and weakness (spastic paralysis), seizures, and loss of intellectual function (dementia). Eye problems similar to those in the neuropathic form may also occur. When people with leptomeningeal transthyretin amyloidosis have associated eye problems, they are said to have the oculoleptomeningeal form.  The cardiac form of transthyretin amyloidosis affects the heart. People with cardiac amyloidosis may have an abnormal heartbeat (arrhythmia), an enlarged heart (cardiomegaly), or orthostatic hypertension. These abnormalities can lead to progressive heart failure and death. Occasionally, people with the cardiac form of transthyretin amyloidosis have mild peripheral neuropathy.
The exact incidence of transthyretin amyloidosis is unknown. In northern Portugal, the incidence of this condition is thought to be one in 538 people. Transthyretin amyloidosis is less common among Americans of European descent, where it is estimated to affect one in 100,000 people. The cardiac form of transthyretin amyloidosis is more common among people with African ancestry. It is estimated that this form affects between 3 percent and 3.9 percent of African Americans and approximately 5 percent of people in some areas of West Africa.
Mutations in the TTR gene cause transthyretin amyloidosis. The TTR gene provides instructions for producing a protein called transthyretin. Transthyretin transports vitamin A (retinol) and a hormone called thyroxine throughout the body. To transport retinol and thyroxine, four transthyretin proteins must be attached (bound) to each other to form a four-protein unit (tetramer). Transthyretin is produced primarily in the liver. A small amount of this protein is produced in an area of the brain called the choroid plexus and in the light-sensitive tissue that lines the back of the eye (the retina).  TTR gene mutations are thought to alter the structure of transthyretin, impairing its ability to bind to other transthyretin proteins and altering its normal function.
These resources address the diagnosis or management of transthyretin amyloidosis:  - Boston University: Amyloid Treatment & Research Program  - Gene Review: Gene Review: Familial Transthyretin Amyloidosis  - Genetic Testing Registry: Amyloidogenic transthyretin amyloidosis  - MedlinePlus Encyclopedia: Autonomic neuropathy   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
Enlarged parietal foramina is an inherited condition of impaired skull development. It is characterized by enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. This condition is due to incomplete bone formation (ossification) within the parietal bones. The openings are symmetrical and circular in shape, ranging in size from a few millimeters to several centimeters wide. Parietal foramina are a normal feature of fetal development, but typically they close before the baby is born, usually by the fifth month of pregnancy. However, in people with this condition, the parietal foramina remain open throughout life.  The enlarged parietal foramina are soft to the touch due to the lack of bone at those areas of the skull. People with enlarged parietal foramina usually do not have any related health problems; however, scalp defects, seizures, and structural brain abnormalities have been noted in a small percentage of affected people. Pressure applied to the openings can lead to severe headaches, and individuals with this condition have an increased risk of brain damage or skull fractures if any trauma is experienced in the area of the openings.  There are two forms of enlarged parietal foramina, called type 1 and type 2, which differ in their genetic cause.
Mutations in the ALX4 gene account for 60 percent of cases of enlarged parietal foramina and mutations in the MSX2 gene account for 40 percent of cases. These genes provide instructions for producing proteins called transcription factors, which are required for proper development throughout the body. Transcription factors attach (bind) to specific regions of DNA and help control the activity of particular genes. The ALX4 and MSX2 transcription factor proteins are involved in regulating genes that are needed in various cell processes in early development.  Mutations in either the ALX4 or MSX2 gene likely impair the ability of their respective transcription factors to bind to DNA. As a result, the regulation of multiple genes is altered, which disrupts a number of necessary cell functions. The processes that guide skull development seem to be particularly sensitive to changes in the activity of these transcription factors.  If the condition is caused by a mutation in the MSX2 gene, it is called enlarged parietal foramina type 1. Mutations in the ALX4 gene cause enlarged parietal foramina type 2. There appears to be no difference in the size of the openings between enlarged parietal foramina types 1 and 2.
These resources address the diagnosis or management of enlarged parietal foramina:  - Gene Review: Gene Review: Enlarged Parietal Foramina  - Genetic Testing Registry: Parietal foramina  - Genetic Testing Registry: Parietal foramina 1  - Genetic Testing Registry: Parietal foramina 2  - MedlinePlus Encyclopedia: Skull of a Newborn   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
Benign essential blepharospasm is a condition characterized by abnormal blinking or spasms of the eyelids. This condition is a type of dystonia, which is a group of movement disorders involving uncontrolled tensing of the muscles (muscle contractions), rhythmic shaking (tremors), and other involuntary movements. Benign essential blepharospasm is different from the common, temporary eyelid twitching that can be caused by fatigue, stress, or caffeine.  The signs and symptoms of benign essential blepharospasm usually appear in mid- to late adulthood and gradually worsen. The first symptoms of the condition include an increased frequency of blinking, dry eyes, and eye irritation that is aggravated by wind, air pollution, sunlight, and other irritants. These symptoms may begin in one eye, but they ultimately affect both eyes. As the condition progresses, spasms of the muscles surrounding the eyes cause involuntary winking or squinting. Affected individuals have increasing difficulty keeping their eyes open, which can lead to severe vision impairment.  In more than half of all people with benign essential blepharospasm, the symptoms of dystonia spread beyond the eyes to affect other facial muscles and muscles in other areas of the body. When people with benign essential blepharospasm also experience involuntary muscle spasms affecting the tongue and jaw (oromandibular dystonia), the combination of signs and symptoms is known as Meige syndrome.
The causes of benign essential blepharospasm are unknown, although the disorder likely results from a combination of genetic and environmental factors. Certain genetic changes probably increase the likelihood of developing this condition, and environmental factors may trigger the signs and symptoms in people who are at risk.  Studies suggest that this condition may be related to other forms of adult-onset dystonia, including uncontrolled twisting of the neck muscles (spasmodic torticollis) and spasms of the hand and finger muscles (writer's cramp). Researchers suspect that benign essential blepharospasm and similar forms of dystonia are associated with malfunction of the basal ganglia, which are structures deep within the brain that help start and control movement.  Although genetic factors are almost certainly involved in benign essential blepharospasm, no genes have been clearly associated with the condition. Several studies have looked at the relationship between common variations (polymorphisms) in the DRD5 and TOR1A genes and the risk of developing benign essential blepharospasm. These studies have had conflicting results, with some showing an association and others finding no connection. Researchers are working to determine which genetic factors are related to this disorder.
Most cases of benign essential blepharospasm are sporadic, which means that the condition occurs in people with no history of this disorder or other forms of dystonia in their family.  Less commonly, benign essential blepharospasm has been found to run in families. In some of these families, the condition appears to have an autosomal dominant pattern of inheritance, which means that one copy of an altered gene in each cell is sufficient to cause the disorder. However, no causative genes have been identified.
These resources address the diagnosis or management of benign essential blepharospasm:  - Benign Essential Blepharospasm Research Foundation: Botulinum Toxin for Treatment of Blepharospasm  - Dystonia Medical Research Foundation: Treatments for dystonia  - Genetic Testing Registry: Blepharospasm  - MedlinePlus Encyclopedia: Eyelid Twitch   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
Tyrosinemia is a genetic disorder characterized by disruptions in the multistep process that breaks down the amino acid tyrosine, a building block of most proteins. If untreated, tyrosine and its byproducts build up in tissues and organs, which can lead to serious health problems.  There are three types of tyrosinemia, which are each distinguished by their symptoms and genetic cause. Tyrosinemia type I, the most severe form of this disorder, is characterized by signs and symptoms that begin in the first few months of life. Affected infants fail to gain weight and grow at the expected rate (failure to thrive) due to poor food tolerance because high-protein foods lead to diarrhea and vomiting. Affected infants may also have yellowing of the skin and whites of the eyes (jaundice), a cabbage-like odor, and an increased tendency to bleed (particularly nosebleeds). Tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones (rickets), and an increased risk of liver cancer (hepatocellular carcinoma). Some affected children have repeated neurologic crises that consist of changes in mental state, reduced sensation in the arms and legs (peripheral neuropathy), abdominal pain, and respiratory failure. These crises can last from 1 to 7 days. Untreated, children with tyrosinemia type I often do not survive past the age of 10.  Tyrosinemia type II can affect the eyes, skin, and mental development. Signs and symptoms often begin in early childhood and include eye pain and redness, excessive tearing, abnormal sensitivity to light (photophobia), and thick, painful skin on the palms of their hands and soles of their feet (palmoplantar hyperkeratosis). About 50 percent of individuals with tyrosinemia type II have some degree of intellectual disability.  Tyrosinemia type III is the rarest of the three types. The characteristic features of this type include intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia).  About 10 percent of newborns have temporarily elevated levels of tyrosine (transient tyrosinemia). In these cases, the cause is not genetic. The most likely causes are vitamin C deficiency or immature liver enzymes due to premature birth.
Worldwide, tyrosinemia type I affects about 1 in 100,000 individuals. This type is more common in Norway where 1 in 60,000 to 74,000 individuals are affected. Tyrosinemia type I is even more common in Quebec, Canada where it occurs in about 1 in 16,000 individuals. In the Saguenay-Lac St. Jean region of Quebec, tyrosinemia type I affects 1 in 1,846 people.  Tyrosinemia type II occurs in fewer than 1 in 250,000 individuals worldwide. Tyrosinemia type III is very rare; only a few cases have been reported.
Mutations in the FAH, TAT, and HPD genes can cause tyrosinemia types I, II, and III, respectively.  In the liver, enzymes break down tyrosine in a five step process, resulting in molecules that are either excreted by the kidneys or used to produce energy or make other substances in the body. The FAH gene provides instructions for the fumarylacetoacetate hydrolase enzyme, which is responsible for the final step of tyrosine breakdown. The enzyme produced from the TAT gene, called tyrosine aminotransferase enzyme, is involved at the first step in the process. The HPD gene provides instructions for making the 4-hydroxyphenylpyruvate dioxygenase enzyme, which is responsible for the second step.  Mutations in the FAH, TAT, or HPD gene cause a decrease in the activity of one of the enzymes in the breakdown of tyrosine. As a result, tyrosine and its byproducts accumulate to toxic levels, which can cause damage and death to cells in the liver, kidneys, nervous system, and other organs.