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Tyrosinemia
Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemia leads to liver failure. Today, tyrosinemia is increasingly detected on newborn screening tests before any symptoms appear. With early and lifelong management involving a low-protein diet, special protein formula, and sometimes medication, people with tyrosinemia develop normally, are healthy, and live normal lives. Cause All tyrosinemias result from dysfunction of various genes in the phenylalanine and tyrosine catabolic pathway, and are inherited in an autosomal-recessive pattern. Type I tyrosinemia results from a mutation in the ''FAH'' gene, which encodes the enzyme fumarylacetoacetase. As a result of ''FAH'' deficiency, the substrate fumarylacetoacetate can accumulate in proximal renal tubular cells and hepatocytes, resulting in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Type I Tyrosinemia
Tyrosinemia type I is a genetic disorder that disrupts the metabolism of the amino acid tyrosine, resulting in damage primarily to the liver along with the kidneys and peripheral nerves. The inability of cells to process tyrosine can lead to chronic liver damage ending in liver failure, as well as renal disease and rickets. Symptoms such as poor growth and enlarged liver are associated with the clinical presentation of the disease. Clinical manifestation of disease occurs typically within the first two years of life. The severity of the disease is correlated with the timing of onset of symptoms, earlier being more severe. Tyrosinemia type I is an autosomal recessive disorder caused by mutations in both copies of the gene encoding the enzyme fumarylacetoacetate hydrolase (FAH). FAH is a metabolic enzyme that catalyzes the conversion of fumarylacetoacetate to fumarate and acetoacetate. It is expressed primarily in the liver and kidney. Loss of FAH activity results in t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosinemia Type II
Tyrosinemia type II is an autosomal recessive condition with onset between ages 2 and 4 years, when painful circumscribed calluses develop on the pressure points of the palm of the hand and sole of the foot. Pathophysiology Type II tyrosinemia is caused by a deficiency of the enzyme tyrosine aminotransferase (), encoded by the gene ''TAT''. Tyrosine aminotransferase is the first in a series of five enzymes that converts tyrosine to smaller molecules, which are excreted by the kidneys or used in reactions that produce energy. This form of the disorder can affect the eyes, skin, and mental development. Symptoms often begin in early childhood and include excessive tearing, abnormal sensitivity to light (photophobia), eye pain and redness, and painful skin lesions on the palms and soles. About half of individuals with type II tyrosinemia are also mentally disabled. Type II tyrosinemia occurs in fewer than 1 in 250,000 individuals. Diagnosis Diagnosis is made based on elevated pl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
4-Hydroxyphenylpyruvate Dioxygenase
4-Hydroxyphenylpyruvate dioxygenase (HPPD), also known as α-ketoisocaproate dioxygenase (KIC dioxygenase), is an Fe(II)-containing non-heme oxygenase that catalyzes the second reaction in the catabolism of tyrosine - the conversion of 4-hydroxyphenylpyruvate into homogentisate. HPPD also catalyzes the conversion of phenylpyruvate to 2-hydroxyphenylacetate and the conversion of α-ketoisocaproate to β-hydroxy β-methylbutyrate. HPPD is an enzyme that is found in nearly all aerobic forms of life. Enzyme mechanism HPPD is categorized within a class of oxygenase enzymes that usually utilize α-ketoglutarate and diatomic oxygen to oxygenate or oxidize a target molecule. However, HPPD differs from most molecules in this class due to the fact that it does not use α-ketoglutarate, and it only utilizes two substrates while adding both atoms of diatomic oxygen into the product, homogentisate. The HPPD reaction occurs through a NIH shift and involves the oxidative decarboxylation ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nitisinone
Nitisinone, sold under the brand name Orfadin among others, is a medication used to slow the effects of hereditary tyrosinemia type 1 (HT-1). Uses Nitisinone is used to treat hereditary tyrosinemia type 1 (HT-1) in patients from all ages, in combination with dietary restriction of tyrosine and phenylalanine. Since its first use for this indication in 1991, it has replaced liver transplantation as the first-line treatment for this ultra rare condition. Adverse effects The most common adverse reactions (>1%) for nitisinone are elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash and alopecia.has several negative side effects; these include but are not limited to: bloated abdomen, dark urine, abdominal pain, feeling of tiredness or weakness, headache, light-colored stools, loss of appetite, weight ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Aminotransferase
Tyrosine aminotransferase (or tyrosine transaminase) is an enzyme present in the liver and catalyzes the conversion of tyrosine to 4-hydroxyphenylpyruvate. L-tyrosine + 2-oxoglutarate \rightleftharpoons 4-hydroxyphenylpyruvate + L-glutamate In humans, the tyrosine aminotransferase protein is encoded by the ''TAT'' gene. A deficiency of the enzyme in humans can result in what is known as type II tyrosinemia, wherein there is an abundance of tyrosine as a result of tyrosine failing to undergo an aminotransferase reaction to form 4-hydroxyphenylpyruvate. Mechanism Structures of the three main molecules involved in chemical reaction catalyzed by the tyrosine aminotransferase enzyme are shown below: the amino acid tyrosine (left), the prosthetic group pyridoxal phosphate (right), and the resulting product 4-hydroxyphenylpyruvate (center). : Each side of the dimer protein includes pyridoxal phosphate (PLP) bonded to the Lys280 residue of the tyrosine aminotransferase mole ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosinemia Type III
Tyrosinemia type III is a rare disorder caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase (), encoded by the gene ''HPD''. This enzyme is abundant in the liver, and smaller amounts are found in the kidneys. It is one of a series of enzymes needed to break down tyrosine. Specifically, 4-hydroxyphenylpyruvate dioxygenase converts a tyrosine byproduct called 4-hydroxyphenylpyruvate to homogentisic acid. Characteristic features of type III tyrosinemia include mild mental retardation, seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...s, and periodic loss of balance and coordination ( intermittent ataxia). Type III tyrosinemia is very rare; only a few cases have been reported. References External links {{Amino acid metabolic pathology Amino acid metab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Succinylacetone
Succinylacetone is a chemical compound that is formed by the oxidation of glycine and is a precursor of methylglyoxal. It is a pathognomonic compound found in the urine of patients with tyrosinemia type 1, which is due to congenital deficiency of an enzyme, fumarylacetoacetate hydrolase. This enzyme is involved in the catabolism of tyrosine, and if deficient, leads to accumulation of fumarylacetoacetate which is subsequently converted to succinylacetone which can be detected in the urine by GCMS. Succinylacetone also inhibits ALA dehydratase (PBG synthase) which increases ALA and precipitates acute neuropathic symptoms, similar to porphyria. References {{Reflist Diketones Carboxylic acids ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alkaptonuria
Alkaptonuria is a rare inherited genetic disease which is caused by a mutation in the ''HGD'' gene for the enzyme homogentisate 1,2-dioxygenase (); if a person inherits an abnormal copy from both parents (it is a recessive condition), the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidized form ''alkapton'' are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves, as well as precipitating as kidney stones and stones in other organs. Symptoms usually develop in people over 30 years old, although the dark discoloration of the urine is present from birth. Apart from treatment of the complications (such as pain relief and joint replacement for the cartilage damage), the drug nitisinone has been found to suppress homogentisic acid production, and research is ongoing as to whether it can ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Low-protein Diet
A low-protein diet is a diet in which people decrease their intake of protein. A low-protein diet is used as a therapy for inherited metabolic disorders, such as phenylketonuria and homocystinuria, and can also be used to treat kidney or liver disease. Low protein consumption appears to reduce the risk of bone breakage, presumably through changes in calcium homeostasis. Consequently, there is no uniform definition of what constitutes low-protein, because the amount and composition of protein for an individual with phenylketonuria would differ substantially from one with homocystinuria or tyrosinemia. History By studying the composition of food in the local population in Germany, Carl von Voit established a standard of 118 grams of protein per day. Russell Henry Chittenden showed that less than half that amount was needed to maintain good health. Protein requirement The daily requirement for humans to remain in nitrogen balance is relatively small. The median human adult requi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ochronosis
Ochronosis is a syndrome caused by the accumulation of homogentisic acid in connective tissues. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. Macroscopically, though, the affected tissues appear bluish-grey because of a light-scattering phenomenon known as the Tyndall effect. The condition is most often associated with alkaptonuria, but can occur from exogenous administration of phenol complex (chemistry), complexes such as hydroquinone. It was first described by Rudolf Virchow in 1865.Findlay GH, et al. Ochronosis. Clinics in Dermatology 1989;7:28-35 Types The two types of ochronosis are endogenous and exogenous. The endogenous variety is an autosomal-recessive disease, known as alkaptonuria, that is caused by a lack of homogentisate oxidase enzyme.CharlÃn, R., Barcaui, C. B., Kac, B. K., Soares, D. B., Rabello-Fonseca, R. and Azulay-Abulafia, L. (2008), Hydroquinone-induced exogenous ochronosis: a report ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inborn Error Of Metabolism
Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrate (biochemistry), substrates) into others (Product (chemistry), products). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or due to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or inherited metabolic disorders. To this concept it's possible to include the new term of Enzymopathy. This term was created following the study of Biochemical Processes, Biodynamic Enzymology, a science based on the study of the enzymes and their derivated products. Finally, ''inborn errors of metabolism'' were studied for the first time by British physician Archibald Garrod (1857â ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Liver Transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic position as the original liver. The surgical procedure is complex, requiring careful harvest of the donor organ and meticulous implantation into the recipient. Liver transplantation is highly regulated, and only performed at designated transplant medical centers by highly trained transplant physicians and supporting medical team. The duration of the surgery ranges from 4 to 18 hours depending on outcome. Favorable outcomes require careful screening for eligible recipient, as well as a well-calibrated live or cadaveric donor match. Medic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
