Druvith/medqa1 huggingface dataset:
Question:  What are the genetic changes related to methylmalonic acidemia ?
Answer: Mutations in the MUT, MMAA, MMAB, MMADHC, and MCEE genes cause methylmalonic acidemia. The long term effects of methylmalonic acidemia depend on which gene is mutated and the severity of the mutation.  About 60 percent of methylmalonic acidemia cases are caused by mutations in the MUT gene. This gene provides instructions for making an enzyme called methylmalonyl CoA mutase. This enzyme works with vitamin B12 (also called cobalamin) to break down several protein building blocks (amino acids), certain lipids, and cholesterol. Mutations in the MUT gene alter the enzyme's structure or reduce the amount of the enzyme, which prevents these molecules from being broken down properly. As a result, a substance called methylmalonyl CoA and other potentially toxic compounds can accumulate in the body's organs and tissues, causing the signs and symptoms of methylmalonic acidemia.  Mutations in the MUT gene that prevent the production of any functional enzyme result in a form of the condition designated mut0. Mut0 is the most severe form of methylmalonic acidemia and has the poorest outcome. Mutations that change the structure of methylmalonyl CoA mutase but do not eliminate its activity cause a form of the condition designated mut-. The mut- form is typically less severe, with more variable symptoms than the mut0 form.  Some cases of methylmalonic acidemia are caused by mutations in the MMAA, MMAB, or MMADHC gene. Proteins produced from the MMAA, MMAB, and MMADHC genes are needed for the proper function of methylmalonyl CoA mutase. Mutations that affect proteins produced from these three genes can impair the activity of methylmalonyl CoA mutase, leading to methylmalonic acidemia.  A few other cases of methylmalonic acidemia are caused by mutations in the MCEE gene. This gene provides instructions for producing an enzyme called methylmalonyl CoA epimerase. Like methylmalonyl CoA mutase, this enzyme also plays a role in the breakdown of amino acids, certain lipids, and cholesterol. Disruption in the function of methylmalonyl CoA epimerase leads to a mild form of methylmalonic acidemia.  It is likely that mutations in other, unidentified genes also cause methylmalonic acidemia.
Question:  Is methylmalonic acidemia inherited ?
Answer: This condition is inherited in an autosomal recessive pattern, which means both copies of the MUT, MMAA, MMAB, MMADHC, or MCEE gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition are carriers of one copy of the mutated gene but do not show signs and symptoms of the condition.
Question:  What are the treatments for methylmalonic acidemia ?
Answer: These resources address the diagnosis or management of methylmalonic acidemia:  - Baby's First Test: Methylmalonic Acidemia (Cobalamin Disorders)  - Baby's First Test: Methylmalonic Acidemia (Methymalonyl-CoA Mutase Deficiency)  - Gene Review: Gene Review: Isolated Methylmalonic Acidemia  - Genetic Testing Registry: Methylmalonic acidemia  - Genetic Testing Registry: Methylmalonic acidemia with homocystinuria cblD  - Genetic Testing Registry: Methylmalonic aciduria cblA type  - Genetic Testing Registry: Methylmalonic aciduria cblB type  - Genetic Testing Registry: Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency  - Genetic Testing Registry: Methylmalonyl-CoA epimerase deficiency  - MedlinePlus Encyclopedia: Methylmalonic acid  - MedlinePlus Encyclopedia: Methylmalonic acidemia  - New England Consortium of Metabolic Programs   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
Question:  What is (are) congenital hepatic fibrosis ?
Answer: Congenital hepatic fibrosis is a disease of the liver that is present from birth. The liver has many important functions, including producing various molecules needed by the body and breaking down other molecules so that their components can be used or eliminated.  Congenital hepatic fibrosis is characterized by malformation of the bile ducts and of the blood vessels of the hepatic portal system. Bile ducts carry bile (a fluid that helps to digest fats) from the liver to the gallbladder and small intestine. The hepatic portal system is a branching network of veins (portal veins) that carry blood from the gastrointestinal tract to the liver for processing.  A buildup of scar tissue (fibrosis) in the portal tracts also occurs in this disorder. Portal tracts are structures in the liver that bundle the vessels through which blood, lymph, and bile flow, and fibrosis in the portal tracts can restrict the normal movement of fluids in these vessels. Lymph is a fluid that helps exchange immune cells, proteins, and other substances between the blood and tissues.  Constriction of the portal veins due to malformation and portal tract fibrosis results in high blood pressure in the hepatic portal system (portal hypertension). Portal hypertension impairs the flow of blood from the gastrointestinal tract, causing an increase in pressure in the veins of the esophagus, stomach, and intestines. These veins may stretch and their walls may become thin, leading to a risk of abnormal bleeding.  People with congenital hepatic fibrosis have an enlarged liver and spleen (hepatosplenomegaly). The liver is abnormally shaped. Affected individuals also have an increased risk of infection of the bile ducts (cholangitis), hard deposits in the gallbladder or bile ducts (gallstones), and cancer of the liver or gallbladder.  Congenital hepatic fibrosis may occur alone, in which case it is called isolated congenital hepatic fibrosis. More frequently, it occurs as a feature of genetic syndromes that also affect the kidneys (the renal system), such as polycystic kidney disease (PKD).
Question:  How many people are affected by congenital hepatic fibrosis ?
Answer: Isolated congenital hepatic fibrosis is rare. Its prevalence is unknown. The total prevalence of syndromes that include congenital hepatic fibrosis as a feature is estimated to be 1 in 10,000 to 20,000 individuals.
Question:  What are the genetic changes related to congenital hepatic fibrosis ?
Answer: Syndromes of which congenital hepatic fibrosis is a feature may be caused by changes in many different genes. The gene changes that cause isolated congenital hepatic fibrosis are unknown.  Congenital hepatic fibrosis is caused by problems in the development of the portal veins and bile ducts. These problems include malformation of embryonic structures called ductal plates. Each ductal plate is a cylinder of cells surrounding branches of the portal veins. During development before birth, the ductal plates normally develop into the network of bile ducts. In congenital hepatic fibrosis, the development of the ductal plates does not proceed normally, resulting in the persistence of immature bile ducts. Branching of the portal vein network also proceeds abnormally, and excess fibrous tissue develops in the portal tracts.  The malformation of the portal veins and bile ducts disrupts the normal flow of blood and bile, which leads to the progressive signs and symptoms of congenital hepatic fibrosis.
Question:  Is congenital hepatic fibrosis inherited ?
Answer: The various syndromes of which congenital hepatic fibrosis is often a feature can have different inheritance patterns. Most of these disorders are inherited in an autosomal recessive pattern, which means both copies of the associated 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. Rare syndromes involving congenital hepatic fibrosis may be inherited in an X-linked recessive pattern, in which the gene associated with the syndrome is located on the X chromosome, which is one of the two sex chromosomes.  In isolated congenital hepatic fibrosis, the inheritance pattern is unknown.
Question:  What are the treatments for congenital hepatic fibrosis ?
Answer: These resources address the diagnosis or management of congenital hepatic fibrosis:  - Gene Review: Gene Review: Congenital Hepatic Fibrosis Overview  - Genetic Testing Registry: Congenital hepatic fibrosis   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
Question:  What is (are) 22q11.2 deletion syndrome ?
Answer: 22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2.  22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. Common signs and symptoms include heart abnormalities that are often present from birth, an opening in the roof of the mouth (a cleft palate), and distinctive facial features. People with 22q11.2 deletion syndrome often experience recurrent infections caused by problems with the immune system, and some develop autoimmune disorders such as rheumatoid arthritis and Graves disease in which the immune system attacks the body's own tissues and organs. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones.  Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and learning disabilities. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia, depression, anxiety, and bipolar disorder. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention deficit hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorders that affect communication and social interaction.  Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.
Question:  How many people are affected by 22q11.2 deletion syndrome ?
Answer: 22q11.2 deletion syndrome affects an estimated 1 in 4,000 people. However, the condition may actually be more common than this estimate because doctors and researchers suspect it is underdiagnosed due to its variable features. The condition may not be identified in people with mild signs and symptoms, or it may be mistaken for other disorders with overlapping features.
Question:  What are the genetic changes related to 22q11.2 deletion syndrome ?
Answer: Most people with 22q11.2 deletion syndrome are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. This region contains 30 to 40 genes, many of which have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is described as a contiguous gene deletion syndrome because it results from the loss of many genes that are close together.  Researchers are working to identify all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, TBX1, is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, hearing loss, and low calcium levels). Some studies suggest that a deletion of this gene may contribute to behavioral problems as well. The loss of another gene, COMT, in the same region of chromosome 22 may also help explain the increased risk of behavioral problems and mental illness. The loss of additional genes in the deleted region likely contributes to the varied features of 22q11.2 deletion syndrome.
Question:  Is 22q11.2 deletion syndrome inherited ?
Answer: The inheritance of 22q11.2 deletion syndrome is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition. Most cases of 22q11.2 deletion syndrome are not inherited, however. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the condition to their children. In about 10 percent of cases, a person with this condition inherits the deletion in chromosome 22 from a parent. In inherited cases, other family members may be affected as well.
Question:  What are the treatments for 22q11.2 deletion syndrome ?
Answer: These resources address the diagnosis or management of 22q11.2 deletion syndrome:  - Gene Review: Gene Review: 22q11.2 Deletion Syndrome  - Genetic Testing Registry: Asymmetric crying face association  - Genetic Testing Registry: DiGeorge sequence  - Genetic Testing Registry: Opitz G/BBB syndrome  - Genetic Testing Registry: Shprintzen syndrome   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
Question:  What is (are) peroxisomal acyl-CoA oxidase deficiency ?
Answer: Peroxisomal acyl-CoA oxidase deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with peroxisomal acyl-CoA oxidase deficiency have weak muscle tone (hypotonia) and seizures. They may have unusual facial features, including widely spaced eyes (hypertelorism), a low nasal bridge, and low-set ears. Extra fingers or toes (polydactyly) or an enlarged liver (hepatomegaly) also occur in some affected individuals.  Most babies with peroxisomal acyl-CoA oxidase deficiency learn to walk and begin speaking, but they experience a gradual loss of these skills (developmental regression), usually beginning between the ages of 1 and 3. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with peroxisomal acyl-CoA oxidase deficiency do not survive past early childhood.
Question:  How many people are affected by peroxisomal acyl-CoA oxidase deficiency ?
Answer: Peroxisomal acyl-CoA oxidase deficiency is a rare disorder. Its prevalence is unknown. Only a few dozen cases have been described in the medical literature.
Question:  What are the genetic changes related to peroxisomal acyl-CoA oxidase deficiency ?
Answer: Peroxisomal acyl-CoA oxidase deficiency is caused by mutations in the ACOX1 gene, which provides instructions for making an enzyme called peroxisomal straight-chain acyl-CoA oxidase. This enzyme is found in sac-like cell structures (organelles) called peroxisomes, which contain a variety of enzymes that break down many different substances. The peroxisomal straight-chain acyl-CoA oxidase enzyme plays a role in the breakdown of certain fat molecules called very long-chain fatty acids (VLCFAs). Specifically, it is involved in the first step of a process called the peroxisomal fatty acid beta-oxidation pathway. This process shortens the VLCFA molecules by two carbon atoms at a time until the VLCFAs are converted to a molecule called acetyl-CoA, which is transported out of the peroxisomes for reuse by the cell.  ACOX1 gene mutations prevent the peroxisomal straight-chain acyl-CoA oxidase enzyme from breaking down VLCFAs efficiently. As a result, these fatty acids accumulate in the body. It is unclear exactly how VLCFA accumulation leads to the specific features of peroxisomal acyl-CoA oxidase deficiency. However, researchers suggest that the abnormal fatty acid accumulation triggers inflammation in the nervous system that leads to the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to a loss of myelin-containing tissue (white matter) in the brain and spinal cord; loss of white matter is described as leukodystrophy. Leukodystrophy is likely involved in the development of the neurological abnormalities that occur in peroxisomal acyl-CoA oxidase deficiency.
Question:  Is peroxisomal acyl-CoA oxidase deficiency inherited ?
Answer: This condition 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.
Question:  What are the treatments for peroxisomal acyl-CoA oxidase deficiency ?
Answer: These resources address the diagnosis or management of peroxisomal acyl-CoA oxidase deficiency:  - Gene Review: Gene Review: Leukodystrophy Overview  - Genetic Testing Registry: Pseudoneonatal adrenoleukodystrophy   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
Question:  What is (are) 3-M syndrome ?
Answer: 3-M syndrome is a disorder that causes short stature (dwarfism), unusual facial features, and skeletal abnormalities. The name of this condition comes from the initials of three researchers who first identified it: Miller, McKusick, and Malvaux.  Individuals with 3-M syndrome grow extremely slowly before birth, and this slow growth continues throughout childhood and adolescence. They have low birth weight and length and remain much smaller than others in their family, growing to an adult height of approximately 120 centimeters to 130 centimeters (4 feet to 4 feet 6 inches). Affected individuals have a normally sized head that looks disproportionately large in comparison with their body. The head may be unusually long and narrow in shape (dolichocephalic).  In addition to short stature, people with 3-M syndrome have a triangle-shaped face with a broad, prominent forehead (frontal bossing) and a pointed chin; the middle of the face is less prominent (hypoplastic midface). They may have large ears, full eyebrows, an upturned nose with a fleshy tip, a long area between the nose and mouth (philtrum), a prominent mouth, and full lips.  Affected individuals may have a short, broad neck and chest with prominent shoulder blades and square shoulders. They may have abnormal spinal curvature such as a rounded upper back that also curves to the side (kyphoscoliosis) or exaggerated curvature of the lower back (hyperlordosis). People with 3-M syndrome may also have unusual curving of the fingers (clinodactyly), short fifth (pinky) fingers, prominent heels, and loose joints. Other skeletal abnormalities, such as unusually slender long bones in the arms and legs, tall, narrow spinal bones (vertebrae), or slightly delayed bone age may be apparent in x-ray images.  3-M syndrome can also affect other body systems. Males with 3-M syndrome may produce reduced amounts of sex hormones (hypogonadism) and occasionally have the urethra opening on the underside of the penis (hypospadias). People with this condition may be at increased risk of developing bulges in blood vessel walls (aneurysms) in the brain. Intelligence is unaffected by 3-M syndrome, and life expectancy is generally normal.  A variant of 3-M syndrome called Yakut short stature syndrome has been identified in an isolated population in Siberia. In addition to having most of the physical features characteristic of 3-M syndrome, people with this form of the disorder are often born with respiratory problems that can be life-threatening in infancy.
Question:  How many people are affected by 3-M syndrome ?
Answer: 3-M syndrome is a rare disorder. About 50 individuals with this disorder have been identified worldwide.
Question:  What are the genetic changes related to 3-M syndrome ?
Answer: Mutations in the CUL7 gene cause 3-M syndrome. The CUL7 gene provides instructions for making a protein called cullin-7. This protein plays a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system.  Cullin-7 helps to assemble a complex known as an E3 ubiquitin ligase. This complex tags damaged and excess proteins with molecules called ubiquitin. Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth.  Mutations in the CUL7 gene that cause 3-M syndrome disrupt the ability of the cullin-7 protein to bring together the components of the E3 ubiquitin ligase complex, interfering with the process of tagging other proteins with ubiquitin (ubiquitination). It is not known how impaired ubiquitination results in the specific signs and symptoms of 3-M syndrome.
Question:  Is 3-M syndrome inherited ?
Answer: This condition 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.
Question:  What are the treatments for 3-M syndrome ?
Answer: These resources address the diagnosis or management of 3-M syndrome:  - Gene Review: Gene Review: 3-M Syndrome  - Genetic Testing Registry: Three M syndrome 1   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