bowang0911/MedQuAD huggingface dataset:
Arginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. People with this disorder have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviors that affect communication and social interaction. They may experience seizures, especially when they have a fever.  Children with arginine:glycine amidinotransferase deficiency may not gain weight and grow at the expected rate (failure to thrive), and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily.
Mutations in the GATM gene cause arginine:glycine amidinotransferase deficiency. The GATM gene provides instructions for making the enzyme arginine:glycine amidinotransferase. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, arginine:glycine amidinotransferase controls the first step of the process. In this step, a compound called guanidinoacetic acid is produced by transferring a cluster of nitrogen and hydrogen atoms called a guanidino group from arginine to glycine. Guanidinoacetic acid is converted to creatine in the second step of the process. Creatine is needed for the body to store and use energy properly.  GATM gene mutations impair the ability of the arginine:glycine amidinotransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of arginine:glycine amidinotransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.
These resources address the diagnosis or management of arginine:glycine amidinotransferase deficiency:  - Gene Review: Gene Review: Creatine Deficiency Syndromes  - Genetic Testing Registry: Arginine:glycine amidinotransferase deficiency   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
Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood. HDL transports cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease.  Additional signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood (mild hypertriglyceridemia); disturbances in nerve function (neuropathy); and enlarged, orange-colored tonsils. Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the clear covering of the eye (corneal clouding), and type 2 diabetes.
Mutations in the ABCA1 gene cause Tangier disease. This gene provides instructions for making a protein that releases cholesterol and phospholipids from cells. These substances are used to make HDL, which transports them to the liver.  Mutations in the ABCA1 gene prevent the release of cholesterol and phospholipids from cells. As a result, these substances accumulate within cells, causing certain body tissues to enlarge and the tonsils to acquire a yellowish-orange color. A buildup of cholesterol can be toxic to cells, leading to impaired cell function or cell death. In addition, the inability to transport cholesterol and phospholipids out of cells results in very low HDL levels, which increases the risk of cardiovascular disease. These combined factors cause the signs and symptoms of Tangier disease.
Prekallikrein deficiency is a blood condition that usually causes no health problems. In people with this condition, blood tests show a prolonged activated partial thromboplastin time (PTT), a result that is typically associated with bleeding problems; however, bleeding problems generally do not occur in prekallikrein deficiency. The condition is usually discovered when blood tests are done for other reasons.  A few people with prekallikrein deficiency have experienced health problems related to blood clotting such as heart attack, stroke, a clot in the deep veins of the arms or legs (deep vein thrombosis), nosebleeds, or excessive bleeding after surgery. However, these are common problems in the general population, and most affected individuals have other risk factors for developing them, so it is unclear whether their occurrence is related to prekallikrein deficiency.
Prekallikrein deficiency is caused by mutations in the KLKB1 gene, which provides instructions for making a protein called prekallikrein. This protein, when converted to an active form called plasma kallikrein in the blood, is involved in the early stages of blood clotting. Plasma kallikrein plays a role in a process called the intrinsic coagulation pathway (also called the contact activation pathway). This pathway turns on (activates) proteins that are needed later in the clotting process. Blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss.  The KLKB1 gene mutations that cause prekallikrein deficiency reduce or eliminate functional plasma kallikrein, which likely impairs the intrinsic coagulation pathway. Researchers suggest that this lack (deficiency) of functional plasma kallikrein protein does not generally cause any symptoms because another process called the extrinsic coagulation pathway (also known as the tissue factor pathway) can compensate for the impaired intrinsic coagulation pathway.
Mutations in the AGPAT2, BSCL2, CAV1, and PTRF genes cause congenital generalized lipodystrophy types 1 through 4, respectively. The proteins produced from these genes play important roles in the development and function of adipocytes, which are the fat-storing cells in adipose tissue. Mutations in any of these genes reduce or eliminate the function of their respective proteins, which impairs the development, structure, or function of adipocytes and makes the body unable to store and use fats properly. These abnormalities of adipose tissue disrupt hormones and affect many of the body's organs, resulting in the varied signs and symptoms of congenital generalized lipodystrophy.  Some of the genes associated with congenital generalized lipodystrophy also play roles in other cells and tissues. For example, the protein produced from the BSCL2 gene is also present in the brain, although its function is unknown. A loss of this protein in the brain may help explain why congenital generalized lipodystrophy type 2 is sometimes associated with intellectual disability.  In some people with congenital generalized lipodystrophy, no mutations have been found in any of the genes listed above. Researchers are looking for additional genetic changes associated with this disorder.
These resources address the diagnosis or management of congenital generalized lipodystrophy:  - Gene Review: Gene Review: Berardinelli-Seip Congenital Lipodystrophy  - Genetic Testing Registry: Berardinelli-Seip congenital lipodystrophy  - MedlinePlus Encyclopedia: Hypertrophic Cardiomypathy  - University of Texas Southwestern Medical Center: Lipodystrophy   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
Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family.  MERRF is characterized by muscle twitches (myoclonus), weakness (myopathy), and progressive stiffness (spasticity). When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells are called ragged-red fibers. Other features of MERRF include recurrent seizures (epilepsy), difficulty coordinating movements (ataxia), a loss of sensation in the extremities (peripheral neuropathy), and slow deterioration of intellectual function (dementia). People with this condition may also develop hearing loss or optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain. Affected individuals sometimes have short stature and a form of heart disease known as cardiomyopathy. Less commonly, people with MERRF develop fatty tumors, called lipomas, just under the surface of the skin.
Mutations in the MT-TK gene are the most common cause of MERRF, occurring in more than 80 percent of all cases. Less frequently, mutations in the MT-TL1, MT-TH, and MT-TS1 genes have been reported to cause the signs and symptoms of MERRF. People with mutations in the MT-TL1, MT-TH, or MT-TS1 gene typically have signs and symptoms of other mitochondrial disorders as well as those of MERRF.  The MT-TK, MT-TL1, MT-TH, and MT-TS1 genes are contained in mitochondrial DNA (mtDNA). Mitochondria are structures within cells that use oxygen to convert the energy from food into a form cells can use through a process called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. The genes associated with MERRF provide instructions for making molecules called transfer RNAs, which are chemical cousins of DNA. These molecules help assemble protein building blocks called amino acids into full-length, functioning proteins within mitochondria. These proteins perform the steps of oxidative phosphorylation.  Mutations that cause MERRF impair the ability of mitochondria to make proteins, use oxygen, and produce energy. These mutations particularly affect organs and tissues with high energy requirements, such as the brain and muscles. Researchers have not determined how changes in mtDNA lead to the specific signs and symptoms of MERRF.  A small percentage of MERRF cases are caused by mutations in other mitochondrial genes, and in some cases the cause of the condition is unknown.
MERRF 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.  In most cases, people with MERRF inherit an altered mitochondrial gene from their mother, who may or may not show symptoms of the disorder. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MERRF.
These resources address the diagnosis or management of MERRF:  - Gene Review: Gene Review: MERRF  - Genetic Testing Registry: Myoclonus with epilepsy with ragged red fibers  - Kennedy Krieger Institute: Mitochondrial Disorders  - MedlinePlus Encyclopedia: Lipoma  - MedlinePlus Encyclopedia: Optic nerve atrophy  - MedlinePlus Encyclopedia: Peripheral Neuropathy  - MitoAction: Tips and Tools for Living with Mito  - United Mitochondrial Disease Foundation: Treatments and Therapies   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
Multiminicore disease is a disorder that primarily affects muscles used for movement (skeletal muscles). This condition causes muscle weakness and related health problems that range from mild to life-threatening.  Researchers have identified at least four forms of multiminicore disease, which can be distinguished by their characteristic signs and symptoms. The most common form, called the classic form, causes muscle weakness beginning in infancy or early childhood. This weakness is most noticeable in muscles of the trunk and neck (axial muscles) and is less severe in the arm and leg muscles. Muscle weakness causes affected infants to appear "floppy" (hypotonic) and can delay the development of motor skills such as sitting, standing, and walking. The disease causes muscles of the ribcage and spine to stiffen. When combined with weakness of the muscles needed for breathing, this stiffness leads to severe or life-threatening respiratory problems. Almost all children with multiminicore disease develop an abnormal curvature of the spine (scoliosis), which appears during childhood and steadily worsens over time.  Other forms of multiminicore disease have different patterns of signs and symptoms. They are less common than the classic form, together accounting for about 25 percent of all cases. The atypical forms of the condition tend to be milder and cause few or no problems with breathing. The moderate form with hand involvement causes muscle weakness and looseness of the joints, particularly in the arms and hands. Another form of multiminicore disease, known as the antenatal form with arthrogryposis, is characterized by stiff, rigid joints throughout the body (arthrogryposis), distinctive facial features, and other birth defects. Paralysis of the eye muscles (external ophthalmoplegia) is a primary feature of another atypical form of multiminicore disease. This form of the condition also causes general muscle weakness and feeding difficulties that appear in the first year of life.  Many people with multiminicore disease also have an increased risk of a developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.  Multiminicore disease gets its name from small, disorganized areas called minicores, which are found in muscle fibers of many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of minicores can help doctors diagnose multiminicore disease, it is unclear how they are related to muscle weakness and the other features of this condition.
Mutations in the RYR1 and SEPN1 genes cause multiminicore disease.  The severe, classic form of multiminicore disease is usually caused by mutations in the SEPN1 gene. This gene provides instructions for making a protein called selenoprotein N. Although its function is unknown, researchers suspect that this protein may play a role in the formation of muscle tissue before birth. It may also be important for normal muscle function after birth. It is unclear, however, how mutations in the SEPN1 gene lead to muscle weakness and the other features of multiminicore disease.  Atypical forms of multiminicore disease often result from mutations in the RYR1 gene. RYR1 mutations are also associated with an increased risk of malignant hyperthermia. This gene provides instructions for making a protein called ryanodine receptor 1, which plays an essential role in skeletal muscles. For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of charged atoms (ions) into muscle cells. In response to certain signals, the ryanodine receptor 1 protein forms a channel that releases stored calcium ions within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract.  Mutations in the RYR1 gene change the structure and function of the ryanodine receptor 1 protein. Some mutations may lead to problems with regulation of the RYR1 channel, while other mutations appear to change the shape of the channel in such a way that calcium ions cannot flow through properly. A disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of multiminicore disease.  In some affected families, the genetic cause of the disorder has not been found. Mutations in genes other than SEPN1 and RYR1 may underlie the condition in these families.
These resources address the diagnosis or management of multiminicore disease:  - Gene Review: Gene Review: Multiminicore Disease  - Genetic Testing Registry: Minicore myopathy with external ophthalmoplegia  - Genetic Testing Registry: Minicore myopathy, antenatal onset, with arthrogryposis  - Genetic Testing Registry: Multiminicore Disease  - MedlinePlus Encyclopedia: Malignant Hyperthermia   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
Episodic ataxia is a group of related conditions that affect the nervous system and cause problems with movement. People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus). Seizures, muscle weakness, and paralysis affecting one side of the body (hemiplegia) may also occur during attacks. Additionally, some affected individuals have a muscle abnormality called myokymia during or between episodes. This abnormality can cause muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin.  Episodes of ataxia and other symptoms can begin anytime from early childhood to adulthood. They can be triggered by environmental factors such as emotional stress, caffeine, alcohol, certain medications, physical activity, and illness. The frequency of attacks ranges from several per day to one or two per year. Between episodes, some affected individuals continue to experience ataxia, which may worsen over time, as well as involuntary eye movements called nystagmus.  Researchers have identified at least seven types of episodic ataxia, designated type 1 through type 7. The types are distinguished by their pattern of signs and symptoms, age of onset, length of attacks, and, when known, genetic cause.
Episodic ataxia can be caused by mutations in several genes that play important roles in the nervous system. Three of these genes, KCNA1, CACNA1A, and CACNB4, provide instructions for making proteins that are involved in the transport of charged atoms (ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. Mutations in the KCNA1, CACNA1A, and CACNB4 genes are responsible for episodic ataxia types 1, 2, and 5, respectively.  Mutations in the SLC1A3 gene have been found to cause episodic ataxia type 6. This gene provides instructions for making a protein that transports a brain chemical (neurotransmitter) called glutamate. Neurotransmitters, including glutamate, allow neurons to communicate by relaying chemical signals from one neuron to another.  Researchers believe that mutations in the KCNA1, CACNA1A, CACNB4, and SLC1A3 genes alter the transport of ions and glutamate in the brain, which causes certain neurons to become overexcited and disrupts normal communication between these cells. Although changes in chemical signaling in the brain underlie the recurrent attacks seen in people with episodic ataxia, it is unclear how mutations in these genes cause the specific features of the disorder.  The genetic causes of episodic ataxia types 3, 4, and 7 have not been identified. Researchers are looking for additional genes that can cause episodic ataxia.
These resources address the diagnosis or management of episodic ataxia:  - Consortium for Clinical Investigations of Neurological Channelopathies (CINCH)  - Gene Review: Gene Review: Episodic Ataxia Type 1  - Gene Review: Gene Review: Episodic Ataxia Type 2  - Genetic Testing Registry: Episodic ataxia type 1  - Genetic Testing Registry: Episodic ataxia type 2  - Genetic Testing Registry: Episodic ataxia, type 3  - Genetic Testing Registry: Episodic ataxia, type 4  - Genetic Testing Registry: Episodic ataxia, type 7  - MedlinePlus Encyclopedia: Movement - uncoordinated  - MedlinePlus Encyclopedia: Vertigo-associated disorders   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
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.