bowang0911/MedQuAD huggingface dataset:
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often.  Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA).  During episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. A small number of people with HIDS have intellectual disability, problems with movement and balance (ataxia), eye problems, and recurrent seizures (epilepsy). Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why people with HIDS have high levels of IgD and IgA. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy.  People with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, progressive ataxia, progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy.
Mutations in the MVK gene cause mevalonate kinase deficiency. The MVK gene provides instructions for making the mevalonate kinase enzyme. This enzyme is involved in the production of cholesterol, which is later converted into steroid hormones and bile acids. Steroid hormones are needed for normal development and reproduction, and bile acids are used to digest fats. Mevalonate kinase also helps to produce other substances that are necessary for certain cellular functions, such as cell growth, cell maturation (differentiation), formation of the cell's structural framework (the cytoskeleton), gene activity (expression), and protein production and modification.  Most MVK gene mutations that cause mevalonate kinase deficiency result in an enzyme that is unstable and folded into an incorrect 3-dimensional shape, leading to a reduction of mevalonate kinase enzyme activity. Despite this shortage (deficiency) of mevalonate kinase activity, people with mevalonate kinase deficiency typically have normal production of cholesterol, steroid hormones, and bile acids.  It is unclear how a lack of mevalonate kinase activity causes the signs and symptoms of this condition. Some researchers believe the features may be due to a buildup of mevalonic acid, the substance that mevalonate kinase normally acts on. Other researchers think that a shortage of the substances produced from mevalonic acid, such as those substances necessary for certain cellular functions, causes the fever episodes and other features of this condition.  The severity of the enzyme deficiency determines the severity of the condition. People who have approximately 1 to 20 percent of normal mevalonate kinase activity typically develop HIDS. Individuals who have less than 1 percent of normal enzyme activity usually develop MVA.
Tarsal-carpal coalition syndrome is a rare, inherited bone disorder that affects primarily the hands and feet. Several individual bones make up each wrist (carpal bones) and ankle (tarsal bones). In tarsal-carpal coalition syndrome, the carpal bones fuse together, as do the tarsal bones, which causes stiffness and immobility of the hands and feet. Symptoms of the condition can become apparent in infancy, and they worsen with age. The severity of the symptoms can vary, even among members of the same family.  In this condition, fusion at the joints between the bones that make up each finger and toe (symphalangism) can also occur. Consequently, the fingers and toes become stiff and difficult to bend. Stiffness of the pinky fingers and toes (fifth digits) is usually noticeable first. The joints at the base of the pinky fingers and toes fuse first, and slowly, the other joints along the length of these digits may also be affected. Progressively, the bones in the fourth, third, and second digits (the ring finger, middle finger, and forefinger, and the corresponding toes) become fused. The thumb and big toe are usually not involved. Affected individuals have increasing trouble forming a fist, and walking often becomes painful and difficult. Occasionally, there is also fusion of bones in the upper and lower arm at the elbow joint (humeroradial fusion). Less common features of tarsal-carpal coalition syndrome include short stature or the development of hearing loss.
Tarsal-carpal coalition syndrome is caused by mutations in the NOG gene, which provides instructions for making a protein called noggin. This protein plays an important role in proper bone and joint development by blocking (inhibiting) signals that stimulate bone formation. The noggin protein attaches (binds) to proteins called bone morphogenetic proteins (BMPs), which keeps the BMPs from triggering signals for the development of bone.  NOG gene mutations that cause tarsal-carpal coalition syndrome reduce the amount of functional noggin protein. With decreased noggin function, BMPs abnormally stimulate bone formation in joint areas, where there should be no bone, causing the bone fusions seen in people with tarsal-carpal coalition syndrome.  Mutations in the NOG gene are involved in several disorders with overlapping signs and symptoms. Because of a shared genetic cause and overlapping features, researchers have suggested that these conditions, including tarsal-carpal coalition syndrome, represent a spectrum of related conditions referred to as NOG-related-symphalangism spectrum disorder (NOG-SSD).
Persistent Mllerian duct syndrome is a disorder of sexual development that affects males. Males with this disorder have normal male reproductive organs, though they also have a uterus and fallopian tubes, which are female reproductive organs. The uterus and fallopian tubes are derived from a structure called the Mllerian duct during development of the fetus. The Mllerian duct usually breaks down during early development in males, but it is retained in those with persistent Mllerian duct syndrome. Affected individuals have the normal chromosomes of a male (46,XY) and normal external male genitalia.  The first noted signs and symptoms in males with persistent Mllerian duct syndrome are usually undescended testes (cryptorchidism) or soft out-pouchings in the lower abdomen (inguinal hernias). The uterus and fallopian tubes are typically discovered when surgery is performed to treat these conditions.  The testes and female reproductive organs can be located in unusual positions in persistent Mllerian duct syndrome. Occasionally, both testes are undescended (bilateral cryptorchidism) and the uterus is in the pelvis. More often, one testis has descended into the scrotum normally, and one has not. Sometimes, the descended testis pulls the fallopian tube and uterus into the track through which it has descended. This creates a condition called hernia uteri inguinalis, a form of inguinal hernia. In other cases, the undescended testis from the other side of the body is also pulled into the same track, forming an inguinal hernia. This condition, called transverse testicular ectopia, is common in people with persistent Mllerian duct syndrome.  Other effects of persistent Mllerian duct syndrome may include the inability to father children (infertility) or blood in the semen (hematospermia). Also, the undescended testes may break down (degenerate) or develop cancer if left untreated.
Most people with persistent Mllerian duct syndrome have mutations in the AMH gene or the AMHR2 gene. The AMH gene provides instructions for making a protein called anti-Mllerian hormone (AMH). The AMHR2 gene provides instructions for making a protein called AMH receptor type 2.  The AMH protein and AMH receptor type 2 protein are involved in male sex differentiation. All fetuses develop the Mllerian duct, the precursor to female reproductive organs. During development of a male fetus, these two proteins work together to induce breakdown (regression) of the Mllerian duct. Mutations in the AMH and AMHR2 genes lead to nonfunctional proteins that cannot signal for regression of the Mllerian duct. As a result of these mutations, the Mllerian duct persists and goes on to form a uterus and fallopian tubes.  Approximately 45 percent of cases of persistent Mllerian duct syndrome are caused by mutations in the AMH gene and are called persistent Mllerian duct syndrome type 1. Approximately 40 percent of cases are caused by mutations in the AMHR2 gene and are called persistent Mllerian duct syndrome type 2. In the remaining 15 percent of cases, no mutations in the AMH and AMHR2 genes have been identified, and the genes involved in causing the condition are unknown.
Deoxyguanosine kinase deficiency is an inherited disorder that can cause liver disease and neurological problems. Researchers have described two forms of this disorder. The majority of affected individuals have the more severe form, which is called hepatocerebral because of the serious problems it causes in the liver and brain.  Newborns with the hepatocerebral form of deoxyguanosine kinase deficiency may have a buildup of lactic acid in the body (lactic acidosis) within the first few days after birth. They may also have weakness, behavior changes such as poor feeding and decreased activity, and vomiting. Affected newborns sometimes have low blood sugar (hypoglycemia) as a result of liver dysfunction. During the first few weeks of life they begin showing other signs of liver disease which may result in liver failure. They also develop progressive neurological problems including very weak muscle tone (severe hypotonia), abnormal eye movements (nystagmus) and the loss of skills they had previously acquired (developmental regression). Children with this form of the disorder usually do not survive past the age of 2 years.  Some individuals with deoxyguanosine kinase deficiency have a milder form of the disorder without severe neurological problems. Liver disease is the primary symptom of this form of the disorder, generally becoming evident during infancy or childhood. Occasionally it first appears after an illness such as a viral infection. Affected individuals may also develop kidney problems. Mild hypotonia is the only neurological effect associated with this form of the disorder.
The DGUOK gene provides instructions for making the enzyme deoxyguanosine kinase. This enzyme plays a critical role in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal function of these structures. Deoxyguanosine kinase is involved in producing and maintaining the building blocks of mitochondrial DNA.  Mutations in the DGUOK gene reduce or eliminate the activity of the deoxyguanosine kinase enzyme. Reduced enzyme activity leads to problems with the production and maintenance of mitochondrial DNA. A reduction in the amount of mitochondrial DNA (known as mitochondrial DNA depletion) impairs mitochondrial function in many of the body's cells and tissues. These problems lead to the neurological and liver dysfunction associated with deoxyguanosine kinase deficiency.
These resources address the diagnosis or management of deoxyguanosine kinase deficiency:  - Gene Review: Gene Review: DGUOK-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form  - Genetic Testing Registry: Mitochondrial DNA-depletion syndrome 3, hepatocerebral  - MedlinePlus Encyclopedia: Hypotonia   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
17 alpha()-hydroxylase/17,20-lyase deficiency is a condition that affects the function of certain hormone-producing glands called the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty and are important for reproduction. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones, including those that control salt levels in the body. People with 17-hydroxylase/17,20-lyase deficiency have an imbalance of many of the hormones that are made in these glands. 17-hydroxylase/17,20-lyase deficiency is one of a group of disorders, known as congenital adrenal hyperplasias, that impair hormone production and disrupt sexual development and maturation.  Hormone imbalances lead to the characteristic signs and symptoms of 17-hydroxylase/17,20-lyase deficiency, which include high blood pressure (hypertension), low levels of potassium in the blood (hypokalemia), and abnormal sexual development. The severity of the features varies. Two forms of the condition are recognized: complete 17-hydroxylase/17,20-lyase deficiency, which is more severe, and partial 17-hydroxylase/17,20-lyase deficiency, which is typically less so.  Males and females are affected by disruptions to sexual development differently. Females (who have two X chromosomes) with 17-hydroxylase/17,20-lyase deficiency are born with normal external female genitalia; however, the internal reproductive organs, including the uterus and ovaries, may be underdeveloped. Women with complete 17-hydroxylase/17,20-lyase deficiency do not develop secondary sex characteristics, such as breasts and pubic hair, and do not menstruate (amenorrhea). Women with partial 17-hydroxylase/17,20-lyase deficiency may develop some secondary sex characteristics; menstruation is typically irregular or absent. Either form of the disorder results in an inability to conceive a baby (infertility).  In affected individuals who are chromosomally male (having an X and a Y chromosome), problems with sexual development lead to abnormalities of the external genitalia. The most severely affected are born with characteristically female external genitalia and are generally raised as females. However, because they do not have female internal reproductive organs, these individuals have amenorrhea and do not develop female secondary sex characteristics. These individuals have testes, but they are abnormally located in the abdomen (undescended). Sometimes, complete 17-hydroxylase/17,20-lyase deficiency leads to external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Males with partial 17-hydroxylase/17,20-lyase deficiency usually have abnormal male genitalia, such as a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Males with either complete or partial 17-hydroxylase/17,20-lyase deficiency are also infertile.
17-hydroxylase/17,20-lyase deficiency is caused by mutations in the CYP17A1 gene. The protein produced from this gene is involved in the formation of steroid hormones. This group of hormones includes sex hormones such as testosterone and estrogen, which are needed for normal sexual development and reproduction; mineralocorticoids, which help regulate the body's salt and water balance; and glucocorticoids, which are involved in maintaining blood sugar levels and regulating the body's response to stress.  Steroid hormones are produced through a series of chemical reactions. The CYP17A1 enzyme performs two important reactions in this process. The enzyme has 17 alpha()-hydroxylase activity, which is important for production of glucocorticoids and sex hormones. CYP17A1 also has 17,20-lyase activity, which is integral to the production of sex hormones.  17-hydroxylase/17,20-lyase deficiency results from a shortage (deficiency) of both enzyme activities. The amount of remaining enzyme activity determines whether a person will have the complete or partial form of the disorder. Individuals with the complete form have CYP17A1 gene mutations that result in the production of an enzyme with very little or no 17-hydroxylase and 17,20-lyase activity. People with the partial form of this condition have CYP17A1 gene mutations that allow some enzyme activity, although at reduced levels.  With little or no 17-hydroxylase activity, production of glucocorticoids is impaired, and instead, mineralocorticoids are produced. An excess of these salt-regulating hormones leads to hypertension and hypokalemia.  Loss of 17,20-lyase activity impairs sex hormone production. Shortage of these hormones disrupts development of the reproductive system and impairs the onset of puberty in males and females with 17-hydroxylase/17,20-lyase deficiency.
Aceruloplasminemia is a disorder in which iron gradually accumulates in the brain and other organs. Iron accumulation in the brain results in neurological problems that generally appear in adulthood and worsen over time.  People with aceruloplasminemia develop a variety of movement problems. They may experience involuntary muscle contractions (dystonia) of the head and neck, resulting in repetitive movements and contortions. Other involuntary movements may also occur, such as rhythmic shaking (tremors), jerking movements (chorea), eyelid twitching (blepharospasm), and grimacing. Affected individuals may also have difficulty with coordination (ataxia). Some develop psychiatric problems and a decline of intellectual function (dementia) in their forties or fifties.  In addition to neurological problems, affected individuals may have diabetes mellitus caused by iron damage to cells in the pancreas that make insulin, a hormone that helps control blood sugar levels. Iron accumulation in the pancreas reduces the cells' ability to make insulin, which impairs blood sugar regulation and leads to the signs and symptoms of diabetes.  Iron accumulation in the tissues and organs results in a corresponding shortage (deficiency) of iron in the blood, leading to a shortage of red blood cells (anemia). Anemia and diabetes usually occur by the time an affected person is in his or her twenties.  Affected individuals also have changes in the light-sensitive tissue at the back of the eye (retina) caused by excess iron. The changes result in small opaque spots and areas of tissue degeneration (atrophy) around the edges of the retina. These abnormalities usually do not affect vision but can be observed during an eye examination.  The specific features of aceruloplasminemia and their severity may vary, even within the same family.
Mutations in the CP gene cause aceruloplasminemia. The CP gene provides instructions for making a protein called ceruloplasmin, which is involved in iron transport and processing. Ceruloplasmin helps move iron from the organs and tissues of the body and prepares it for incorporation into a molecule called transferrin, which transports it to red blood cells to help carry oxygen.  CP gene mutations result in the production of ceruloplasmin protein that is unstable or nonfunctional, or they prevent the protein from being released (secreted) by the cells in which it is made. When ceruloplasmin is unavailable, transport of iron out of the body's tissues is impaired. The resulting iron accumulation damages cells in those tissues, leading to neurological dysfunction, and the other health problems seen in aceruloplasminemia.
Complement factor I deficiency is a disorder that affects the immune system. People with this condition are prone to recurrent infections, including infections of the upper respiratory tract, ears, skin, and urinary tract. They may also contract more serious infections such as pneumonia, meningitis, and sepsis, which may be life-threatening.  Some people with complement factor I deficiency have a kidney disorder called glomerulonephritis with isolated C3 deposits. Complement factor I deficiency can also be associated with autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus (SLE). Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs.
Complement factor I deficiency is caused by mutations in the CFI gene. This gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. This system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells. Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed.  Mutations in the CFI gene that cause complement factor I deficiency result in abnormal, nonfunctional, or absent complement factor I. The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. In addition, the immune system may malfunction and attack its own tissues, resulting in autoimmune disorders.