bowang0911/MedQuAD huggingface dataset:
Autosomal recessive congenital methemoglobinemia is caused by mutations in the CYB5R3 gene. This gene provides instruction for making an enzyme called cytochrome b5 reductase 3. This enzyme is involved in transferring negatively charged particles called electrons from one molecule to another. Two versions (isoforms) of this enzyme are produced from the CYB5R3 gene. The soluble isoform is present only in red blood cells, and the membrane-bound isoform is found in all other cell types.  Each hemoglobin molecule contains four iron atoms, which are needed to carry oxygen. In normal red blood cells, the iron in hemoglobin is ferrous (Fe2+), but it can spontaneously become ferric (Fe3+). When hemoglobin contains ferric iron, it is methemoglobin. The soluble isoform of cytochrome b5 reductase 3 changes ferric iron back to ferrous iron so hemoglobin can deliver oxygen to tissues. Normally, red blood cells contain less than 2 percent methemoglobin.  The membrane-bound isoform is widely used in the body. This isoform is necessary for many chemical reactions, including the breakdown and formation of fatty acids, the formation of cholesterol, and the breakdown of various molecules and drugs.  CYB5R3 gene mutations that cause autosomal recessive congenital methemoglobinemia type I typically reduce enzyme activity or stability. As a result, the enzyme cannot efficiently change ferric iron to ferrous iron, leading to a 10 to 50 percent increase in methemoglobin within red blood cells. This increase in methemoglobin and the corresponding decrease in normal hemoglobin reduces the amount of oxygen delivered to tissues. The altered enzyme activity affects only red blood cells because other cells can compensate for a decrease in enzyme activity, but red blood cells cannot.  Mutations that cause autosomal recessive congenital methemoglobinemia type II usually result in a complete loss of enzyme activity. Cells cannot compensate for a complete loss of this enzyme, which results in a 10 to 70 percent increase in methemoglobin within red blood cells. This increase in methemoglobin and the corresponding decrease in normal hemoglobin leads to cyanosis. The lack of enzyme activity in other cells leads to the neurological features associated with type II. Researchers suspect that the neurological problems are caused by impaired fatty acid and cholesterol formation, which reduces the production of a fatty substance called myelin. Myelin insulates nerve cells and promotes the rapid transmission of nerve impulses. This reduced ability to form myelin (hypomyelination) leads to a loss of nerve cells, particularly in the brain. The loss of these cells likely contributes to the encephalopathy and movement disorders characteristic of autosomal recessive congenital methemoglobinemia type II.
These resources address the diagnosis or management of autosomal recessive congenital methemoglobinemia:  - Genetic Testing Registry: METHEMOGLOBINEMIA, TYPE I  - Genetic Testing Registry: Methemoglobinemia type 2  - KidsHealth from Nemours: Blood Test: Hemoglobin  - MedlinePlus Encyclopedia: Hemoglobin  - MedlinePlus Encyclopedia: Methemoglobinemia   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
Hystrix-like ichthyosis with deafness (HID) is a disorder characterized by dry, scaly skin (ichthyosis) and hearing loss that is usually profound. Hystrix-like means resembling a porcupine; in this type of ichthyosis, the scales may be thick and spiky, giving the appearance of porcupine quills.  Newborns with HID typically develop reddened skin. The skin abnormalities worsen over time, and the ichthyosis eventually covers most of the body, although the palms of the hands and soles of the feet are usually only mildly affected. Breaks in the skin may occur and in severe cases can lead to life-threatening infections. Affected individuals have an increased risk of developing a type of skin cancer called squamous cell carcinoma, which can also affect mucous membranes such as the inner lining of the mouth. People with HID may also have patchy hair loss caused by scarring on particular areas of skin.
HID is caused by mutations in the GJB2 gene. This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.  Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth and maturation of the outermost layer of skin (the epidermis).  At least one GJB2 gene mutation has been identified in people with HID. This mutation changes a single protein building block (amino acid) in connexin 26. The mutation is thought to result in channels that constantly leak ions, which impairs the health of the cells and increases cell death. Death of cells in the skin and the inner ear may underlie the signs and symptoms of HID.  Because the GJB2 gene mutation identified in people with HID also occurs in keratitis-ichthyosis-deafness syndrome (KID syndrome), a disorder with similar features and the addition of eye abnormalities, many researchers categorize KID syndrome and HID as a single disorder, which they call KID/HID. It is not known why some people with this mutation have eye problems while others do not.
These resources address the diagnosis or management of hystrix-like ichthyosis with deafness:  - Foundation for Ichthyosis and Related Skin Types: Ichthyosis Hystrix  - Genetic Testing Registry: Hystrix-like ichthyosis with deafness   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
48,XXYY syndrome is a chromosomal condition that causes medical and behavioral problems in males.  48,XXYY disrupts male sexual development. Adolescent and adult males with this condition typically have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development. A shortage of testosterone during puberty can lead to reduced facial and body hair, poor muscle development, low energy levels, and an increased risk for breast enlargement (gynecomastia). Because their testes do not function normally, males with 48, XXYY syndrome have an inability to father children (infertility).  48,XXYY syndrome can affect other parts of the body as well. Males with 48,XXYY syndrome are often taller than other males their age. They tend to develop a tremor that typically starts in adolescence and worsens with age. Dental problems are frequently seen with this condition; they include delayed appearance of the primary (baby) or secondary (adult) teeth, thin tooth enamel, crowded and/or misaligned teeth, and multiple cavities. As affected males get older, they may develop a narrowing of the blood vessels in the legs, called peripheral vascular disease. Peripheral vascular disease can cause skin ulcers to form. Affected males are also at risk for developing a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the legs. Additionally, males with 48,XXYY syndrome may have flat feet (pes planus), elbow abnormalities, allergies, asthma, type 2 diabetes, seizures, and congenital heart defects.  Most males with 48,XXYY syndrome have some degree of difficulty with speech and language development. Learning disabilities, especially reading problems, are very common in males with this disorder. Affected males seem to perform better at tasks focused on math, visual-spatial skills such as puzzles, and memorization of locations or directions. Some boys with 48,XXYY syndrome have delayed development of motor skills such as sitting, standing, and walking that can lead to poor coordination. Affected males have higher than average rates of behavioral disorders, such as attention deficit hyperactivity disorder (ADHD); mood disorders, including anxiety and bipolar disorder; and/or autism spectrum disorders, which affect communication and social interaction.
48,XXYY syndrome is a condition related to the X and Y chromosomes (the sex chromosomes). People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY). 48,XXYY syndrome results from the presence of an extra copy of both sex chromosomes in each of a male's cells (48,XXYY). Extra copies of genes on the X chromosome interfere with male sexual development, preventing the testes from functioning normally and reducing the levels of testosterone. Many genes are found only on the X or Y chromosome, but genes in areas known as the pseudoautosomal regions are present on both sex chromosomes. Extra copies of genes from the pseudoautosomal regions of the extra X and Y chromosome contribute to the signs and symptoms of 48,XXYY syndrome; however, the specific genes have not been identified.
This condition is not inherited; it usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. In 48,XXYY syndrome, the extra sex chromosomes almost always come from a sperm cell. Nondisjunction may cause a sperm cell to gain two extra sex chromosomes, resulting in a sperm cell with three sex chromosomes (one X and two Y chromosomes). If that sperm cell fertilizes a normal egg cell with one X chromosome, the resulting child will have two X chromosomes and two Y chromosomes in each of the body's cells.  In a small percentage of cases, 48,XXYY syndrome results from nondisjunction of the sex chromosomes in a 46,XY embryo very soon after fertilization has occurred. This means that an normal sperm cell with one Y chromosome fertilized a normal egg cell with one X chromosome, but right after fertilization nondisjunction of the sex chromosomes caused the embryo to gain two extra sex chromosomes, resulting in a 48,XXYY embryo.
X-linked spondyloepiphyseal dysplasia tarda is a condition that impairs bone growth and occurs almost exclusively in males. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends (epiphyses) of long bones in the arms and legs. "Tarda" indicates that signs and symptoms of this condition are not present at birth, but appear later in childhood, typically between ages 6 and 10.  Males with X-linked spondyloepiphyseal dysplasia tarda have skeletal abnormalities and short stature. Affected boys grow steadily until late childhood, when their growth slows. Male adult height ranges from 4 feet 10 inches to 5 feet 6 inches. Individuals with X-linked spondyloepiphyseal dysplasia tarda have a short trunk and neck, and their arms appear disproportionately long. Impaired growth of the spinal bones (vertebrae) causes the short stature seen in this disorder. The spinal abnormalities include flattened vertebrae (platyspondyly) with hump-shaped bulges, progressive thinning of the discs between vertebrae, and an abnormal curvature of the spine (scoliosis or kyphosis). Other skeletal features of X-linked spondyloepiphyseal dysplasia tarda include an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara); a broad, barrel-shaped chest; and decreased mobility of the elbow and hip joints. Arthritis often develops in early adulthood, typically affecting the hip joints and spine.
Mutations in the TRAPPC2 gene (often called the SEDL gene) cause X-linked spondyloepiphyseal dysplasia tarda. The TRAPPC2 gene provides instructions for producing the protein sedlin. The function of sedlin is unclear. Researchers believe that sedlin is part of a large molecule called the trafficking protein particle (TRAPP) complex, which plays a role in the transport of proteins between various cell compartments (organelles). Because sedlin is active (expressed) in cells throughout the body; it is unclear why mutations in the TRAPPC2 gene affect only bone growth.
X-linked spondyloepiphyseal dysplasia tarda is inherited in an X-linked recessive pattern. The TRAPPC2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. In rare cases, however, females who carry a TRAPPC2 mutation may develop arthritis in early adulthood.
These resources address the diagnosis or management of X-linked spondyloepiphyseal dysplasia tarda:  - Gene Review: Gene Review: X-Linked Spondyloepiphyseal Dysplasia Tarda  - Genetic Testing Registry: Spondyloepiphyseal dysplasia tarda   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
Fuchs endothelial dystrophy is a condition that causes vision problems. The first symptom of this condition is typically blurred vision in the morning that usually clears during the day. Over time, affected individuals lose the ability to see details (visual acuity). People with Fuchs endothelial dystrophy also become sensitive to bright lights.  Fuchs endothelial dystrophy specifically affects the front surface of the eye called the cornea. Deposits called guttae, which are detectable during an eye exam, form in the middle of the cornea and eventually spread. These guttae contribute to the loss of cells in the cornea, leading to vision problems. Tiny blisters may develop on the cornea, which can burst and cause eye pain.  The signs and symptoms of Fuchs endothelial dystrophy usually begin in a person's forties or fifties. A very rare early-onset variant of this condition starts to affect vision in a person's twenties.
The genetics of Fuchs endothelial dystrophy are unclear. Researchers have identified regions of a few chromosomes and several genes that they think may play a role in the development of Fuchs endothelial dystrophy, but many of these associations need to be further tested.  Fuchs endothelial dystrophy affects a thin layer of cells that line the back of the cornea, called corneal endothelial cells. These cells regulate the amount of fluid inside the cornea. An appropriate fluid balance in the cornea is necessary for clear vision. Fuchs endothelial dystrophy occurs when the endothelial cells die, and the cornea becomes swollen with too much fluid. Corneal endothelial cells continue to die over time, resulting in further vision problems. It is thought that mutations in genes that are active (expressed) primarily in corneal endothelial cells or surrounding tissue may lead to the death of corneal endothelial cells, resulting in Fuchs endothelial dystrophy.  Some cases of the early-onset variant of Fuchs endothelial dystrophy are caused by mutations in the COL8A2 gene. This gene provides instructions for making a protein that is part of type VIII collagen. Type VIII collagen is largely found within the cornea, surrounding the endothelial cells. Specifically, type VIII collagen is a major component of a tissue at the back of the cornea, called Descemet's membrane. This membrane is a thin, sheet-like structure that separates and supports corneal endothelial cells. COL8A2 gene mutations that cause the early-onset variant of Fuchs endothelial dystrophy lead to an abnormal Descemet's membrane, which causes the cells to die and leads to the vision problems in people with this condition.  Mutations in unidentified genes are also likely to cause the early-onset variant of Fuchs endothelial dystrophy. The genetic causes of the late-onset form of the disorder are unknown.
In some cases, Fuchs endothelial dystrophy appears to be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When this condition is caused by a mutation in the COL8A2 gene, it is inherited in an autosomal dominant pattern. In addition, an autosomal dominant inheritance pattern is apparent in some situations in which the condition is caused by alterations in an unknown gene.  In many families, the inheritance pattern is unknown.  Some cases result from new mutations in a gene and occur in people with no history of the disorder in their family.
These resources address the diagnosis or management of Fuchs endothelial dystrophy:  - Duke Eye Center: Corneal Disease  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial 1  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 2  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 3  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 4  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 5  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 6  - Genetic Testing Registry: Corneal dystrophy, Fuchs endothelial, 7  - MedlinePlus Encyclopedia: Fuchs Dystrophy   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
Weyers acrofacial dysostosis is a disorder that affects the development of the teeth, nails, and bones. Dental abnormalities can include small, peg-shaped teeth; fewer teeth than normal (hypodontia); and one front tooth instead of two (a single central incisor). Additionally, the lower jaw (mandible) may be abnormally shaped. People with Weyers acrofacial dysostosis have abnormally small or malformed fingernails and toenails. Most people with the condition are relatively short, and they may have extra fingers or toes (polydactyly).  The features of Weyers acrofacial dysostosis overlap with those of another, more severe condition called Ellis-van Creveld syndrome. In addition to tooth and nail abnormalities, people with Ellis-van Creveld syndrome have very short stature and are often born with heart defects. The two conditions are caused by mutations in the same genes.
Most cases of Weyers acrofacial dysostosis result from mutations in the EVC2 gene. A mutation in a similar gene, EVC, has been found in at least one person with the characteristic features of the disorder. Little is known about the function of the EVC and EVC2 genes, although they appear to play important roles in cell-to-cell signaling during development. In particular, the proteins produced from these genes are thought to help regulate the Sonic Hedgehog signaling pathway. This pathway plays roles in cell growth, cell specialization, and the normal shaping (patterning) of many parts of the body.  The mutations that cause Weyers acrofacial dysostosis result in the production of an abnormal EVC or EVC2 protein. It is unclear how the abnormal proteins lead to the specific signs and symptoms of this condition. Studies suggest that they interfere with Sonic Hedgehog signaling in the developing embryo, disrupting the formation and growth of the teeth, nails, and bones.
Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems.  The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent intellectual disability. Seizures, delayed development, behavioral problems, and psychiatric disorders are also common. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.  Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller risk of brain damage. People with very mild cases may not require treatment with a low-phenylalanine diet.  Babies born to mothers with PKU and uncontrolled phenylalanine levels (women who no longer follow a low-phenylalanine diet) have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth. These infants may also have a low birth weight and grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, an abnormally small head size (microcephaly), and behavioral problems. Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.
Mutations in the PAH gene cause phenylketonuria.  The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase. This enzyme converts the amino acid phenylalanine to other important compounds in the body. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet is not processed effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.  Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious medical problems. Mutations in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition, such as variant PKU or non-PKU hyperphenylalaninemia.  Changes in other genes may influence the severity of PKU, but little is known about these additional genetic factors.
These resources address the diagnosis or management of phenylketonuria:  - Baby's First Test  - Gene Review: Gene Review: Phenylalanine Hydroxylase Deficiency  - Genetic Testing Registry: Phenylketonuria  - MedlinePlus Encyclopedia: Phenylketonuria  - MedlinePlus Encyclopedia: Serum Phenylalanine Screening   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