Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. Parents of children with arginase deficiency rarely have the condition themselves. Arginase is the last enzyme of the urea cycle that breaks down the amino acid arginine produced by the urea cycle, into two molecules, urea and ornithine. Arginase1 deficiency nord national organization for. It is characterized by lowered activity of arginase in hepatic cells. A person with the genetic defect and not the disorder is known as a carrier. A phase 12 study of aeb1102 in patients with arginase i.
What is the life expectancy of someone with arginase. Human recombinant arginase enzyme reduces plasma arginine in. In children with arginase deficiency, neither of these genes works correctly. Arginase deficiency definition of arginase deficiency by. Many physiologic and pathophysiologic processes are modulated by arginine availability, which can be regulated by arginase. This disorder must be inherited by both the mother and the father. Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Overview arginase deficiency is the least common of the urea cycle disorders. Arginase deficiency does not cause symptoms in the newborn. Cederbaum sd, moedjono sj, shaw knf, carter m, naylor e, walser m 1982 treatment of hyperargininaemia due to arginase deficiency with a chemically defined diet. This study is designed to evaluate the safety and tolerability of iv administration of aeb1102 for the treatment of pediatric and adult patients with arginase i deficiency and. Arginase 1 arg1 deficiency is a rare autosomal recessive disorder that affects the liverbased urea cycle, leading to impaired ureagenesis. Rbc arginase deficiency with normal liver arginase activity has been shown to segregate as an autosomal codominant trait in macaca fascicularis established and bred in captivity. However, arginase deficiency is the least likely of the urea cycle disorders to cause neonatal hyperammonemia.
An understanding of the conditions that result in elevated arginase activity as well as the consequences of arginine deficiency is essential for design of effective nutritional support for disease. Arginase deficiency arginase deficiency is an inherited disorder that causes the amino acid arginine a building block of proteins and ammonia to accumulate gradually in the blood. Instead, each parent has a single nonworking gene for arginase deficiency. Arginase deficiency typically refers to decreased function of arginase i, the liver isoform of arginase. This means that to be affected, a person must have a diseasecausing mutation in both copies of the gene associated with arginase deficiency. Ornithine transcarbamylase an overview sciencedirect topics. Arginase1 deficiency is inherited as an autosomal recessive genetic disorder. Arginase definition of arginase by the free dictionary. On the level of the whole organism, arginine is a nonessential amino acid for healthy adult humans, but it has to be supplemented during growth or various disease states 6, 7 and has thus been characterized as a semi or conditionally essential amino acid.
The arginase 1 deficiency facebook page is a community where you can learn more information about arginase 1 deficiency and connect with. Facebook is showing information to help you better understand the purpose of a page. Jul 02, 2015 a phase 12 openlabel study in patients with arginase i deficiency to investigate the safety, pharmacokinetics, and pharmacodynamics of intravenous aeb1102. Arginase deficiency hyperargininemia arginase is the sixth and final enzyme of the urea cycle and converts arginine to urea and ornithine. Most commonly, birth and early childhood are normal.
This entity also manifests itself in a fashion somewhat different from other disorders in the group see physical. Arginase enzyme has an advantage when there is tetrahydorbiopterin bh4 deficiency or arginine deficiency. Arginase definition of arginase by medical dictionary. Arginase deficiency is an inherited disorder that causes the amino acid arginine a building block of proteins and ammonia to accumulate gradually in the blood. Arginase deficiency is typically not characterized by severe increase in ammonia.
For language access assistance, contact the ncats public information officer. Increased levels of arginase activity in blood have been associated with liver damage. Arginase deficiency is one of the least frequent of the urea cycle disorders with an incidence between 1. May 02, 2018 arginase deficiency disorder is a rare, genetic disorder that is characterized by the lack of an enzyme, arginase, which is important for body metabolism the predisposing risk factor of arginase deficiency disorder is inheriting two mutated copies of the gene that causes the disorder from the parents. Arginase deficiency is inherited in an autosomal recessive manner. Request pdf hyperargininemia due to liver arginase deficiency the urea cycle is a series of six reactions necessary to rid the body of the nitrogen generated. A deficiency, usually near complete absence, of activity of arginase, blocks the final step of the cycle.
Arginase1 arg1 deficiency is a rare autosomal recessive disorder that affects the liverbased urea cycle, leading to impaired ureagenesis. If you have problems viewing pdf files, download the latest version of adobe reader. Rescue of the functional alterations of motor cortical circuits in arginase deficiency by neonatal gene therapy. The primary endpoint of the trial is safety and tolerability of intravenous administration of aeb1102 in patients with arginase i deficiency. Two separate isozymes of the enzyme arginase have been reported. Arginase deficiency argininemia statpearls ncbi bookshelf. Loss of previously acquired developmental milestones. Apr 25, 2017 arginase deficiency is inherited in an autosomal recessive manner. Arginase is one of six enzymes that play a role in the breakdown and removal of nitrogen from the body, a process known as the urea cycle. These children inherit one nonworking arg1 gene for the condition from each parent. It is a key enzyme of the urea cycle that catalyses the conversion of larginine into lornithine and urea, the final cytosolic reaction of urea formation in the mammalian liver 1. The shape of an enzyme affects its ability to control a chemical reaction. Symptoms of arg1 deficiency include increased plasma level of arginine and.
May 12, 2020 a mutated arg1 gene may result in an arginase enzyme that is unstable, shorter than usual or the wrong shape, or may prevent the enzyme from being produced at all. A phase 12 openlabel study in patients with arginase i deficiency to investigate the safety, pharmacokinetics, and pharmacodynamics of intravenous aeb1102. Ammonia, which is formed when proteins are broken down in the body, is. Arginase1 arg1 deficiency is a rare autosomal recessive disorder that. Humans express two distinct arginase genes identified as arg1 and arg2 that encode the arginase type i and type ii enzymes, respectively. Arginase activity assay kit catalog number mak112 technical bulletin product description arginase is a manganesecontaining enzyme that catalyzes the conversion of arginine to urea and ornithine.
Arginase bladder contains ingredients which have been used to nutritionally support the bladder and various aspects of urine metabolism. In addition to raising serum arginine levels, arginase deficiency can lead to raised ammonia levels 3. Arg1 deficiency, arginase deficiency disease, argininemia,hyperargininemia arginase deficiency is an inherited disorder that causes the amino acid arginine to accumulate gradually in the blood. Cantero g, liu xb, mervis rf, lazaro mt, cederbaum sd, golshani p, et al. Argininemia, is an autosomal recessive urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood. Unlike other urea cycle defects, argininemia usually presents after 1 year of age with progressive spastic paraparesis, developmental delays, seizures that become progressively harder to control, and sometimes acquired microcephaly and. Jci insight hepatic arginase deficiency fosters dysmyelination. Arginase deficiency in multiple tissues in argininemia. A block in this enzyme activity results in high levels of arginine.
Arginase 1 deficiency is a rare inherited disorder characterized by complete or partial lack of the enzyme arginase in the liver and red blood cells. Arginase as a potential target in the treatment of. This deficiency is commonly referred to as hyperargininemia or arginemia. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. A 5 912yearold mexican female with argininemia presented at 4 years of age with severe growth retardation, microcephaly, mental retardation, loss of ability to walk, spasticity and epileptiform electroencephalogram. Jan 07, 2019 arginase deficiency is thought to be the least common of the urea cycle disorders. If the arginase enzyme is misshapen or missing, it cannot fulfill its role in the urea cycle. Arginase deficiency disorder is cause by an inherited gene defect.
Disorders of arginine metabolism are included in a larger group of disorders, known as urea cycle disorders. Arginase1 deficiency nord national organization for rare. Disorders of arginine metabolism are included in a larger group of. The urea cycle is a sequence of reactions that occurs in liver cells. World map of arginase deficiency argininemia find people with arginase deficiency argininemia through the map. Based on sequence analysis, arginase is probably a primordial enzyme that was present in the universal common ancestor ouzounis and krypides 1994. Aeglea biotherapeutics doses first patients in phase 1 trial. Although a catastrophic neonatal presentation is very uncommon in arginase deficiency, dietary protein intolerance is an early sign and should not be overlooked. Arginase exists in two distinct isoforms, arginase i and ii, that share. Introduction the urea cycle disorders are a group of rare disorders affecting the urea cycle, a series of biochemical processes in which nitrogen is converted into urea and removed from the body through the urine. Arginase ii is a mitochondrial enzyme, and is expressed primarily in the kidney romero et al.
Arginase is a manganese metalloenzyme that hydrolyses larginine to urea and lornithine. Characteristic phenotypic features of arginase deficiency include spastic diplegia, seizures, intellectual disability ranging from mild to severe, selfprotein restriction and growth deficiency 1, 2. Urea is excreted from the body, and ornithine is recycled. As plasma arginase activity is not routinely assayed by clinical chemistry laboratories, the full range of conditions in which it becomes elevated is not yet known. Arginase deficiency genetic and rare diseases information. Arginase deficiency is thought to be the least common of the urea cycle disorders. Pdf argininemia is a rare autosomal recessive metabolic disorder caused by. It results from the absence of the enzyme arginase 1, which breaks down arginine to ornithine and urea, leading to episodic hyperammonemia. Arginase deficiency belongs to a class of genetic diseases called urea cycle disorders. Symptoms poor growth present in all the people who have arginase deficiency. Hyperargininemia due to arginase deficiency is an inherited autosomal recessive disease. Jan 07, 2019 diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Obetadglucopyranoside pg, inhibits arginase activity.
Arginase i mrna therapy a novel approach to rescue arginase 1. The nervous system is especially sensitive to the effects of excess ammonia. A low level of arginase is normally present in plasma of healthy individuals but can become elevated in certain conditions or diseases table 1. Arginase catalyzes the conversion of arginine to ornithine and urea, completing the last step in the urea cycle. Arginase deficiency disorder is a rare, genetic disorder that is characterized by the lack of an enzyme, arginase, which is important for body metabolism the predisposing risk factor of arginase deficiency disorder is inheriting two mutated copies of the.
Arginase activity assay kit mak112 technical bulletin. Arginase i arg1 deficiency, a rare autosomal recessive disorder of ureagenesis has classically been the phenotypic exception within urea cycle disorders. Arginase i is located in the cytoplasm and expressed in the liver as part of the urea cycle. Arginase 1, also known as liver arginase, is a binuclear manganese metalloenzyme.
World map of arginase deficiencyargininemia find people with arginase deficiencyargininemia through the map. Mouse model for human arginase deficiency europe pmc article. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. Oct 14, 2015 arginase 1 arg1 deficiency is a rare autosomal recessive disorder that affects the liverbased urea cycle, leading to impaired ureagenesis. Pdf a novel mutation in arg1 gene is responsible for arginase. The phase 1, multicenter, single arm, open label, dose escalation trial of aeb1102 will enroll up to six patients, 18 years of age or older, with arginase i deficiency. Arginase is an enzyme urea cycle that produces urea and ornithine from arginine. Join the arginase deficiency argininemia community. Patients with arg1 deficiency typically present later in life with spasticity, seizures and failure to thrive. A mutated arg1 gene may result in an arginase enzyme that is unstable, shorter than usual or the wrong shape, or may prevent the enzyme from being produced at all. Hyperargininemia due to liver arginase deficiency request pdf.
The parents of a person with arginase deficiency usually each carry one mutated copy of the gene and are referred to as carriers. Arginase deficiency ad is inherited as an autosomal recessive disorder resulting from mutations in the arginase gene. Arg1 deficient patients can infrequently experience hyperammonemia as well. Hepatic arginase deficiency fosters dysmyelination during postnatal. Deficiency of liver arginase ai causes hyperargininemia omim 207800, a disorder characterized by progressive mental impairment. Two isoforms of arginase are present in most mammals, which differ in their tissue distribution and subcellular localization. Arginase is a target for treating cardiovascular disease. An enzyme found primarily in the liver that catalyzes the hydrolysis of arginine to form urea and ornithine. Recombinant human arginase 1arg1 protein, cf 5868ar010. Michels and beaudet 1978 reported an affected mexican child with growth retardation, microcephaly, mental retardation, spasticity, and epileptiform discharges on eeg. Ucdc healthcare professionals disorder definitions.
Argininemia arginase deficiency, hyperargininemia what are the characteristics of argininemia. Arginase deficiency argininemia is an autosomal recessive metabolic disorder characterized by hyperammonemia secondary to arginine. Sep 15, 2016 the phase 1, multicenter, single arm, open label, dose escalation trial of aeb1102 will enroll up to six patients, 18 years of age or older, with arginase i deficiency. The disorder is hereditary and autosomal recessive. Enable javascript to view the expandcollapse boxes. Arginase1 deficiency is a rare inherited disorder characterized by complete or partial lack of the enzyme arginase in the liver and red blood cells. The primary endpoint of the trial is safety and tolerability of intravenous administration of aeb1102 in. Average arginine ingestion with a western style diet is around 4. Arginase deficiency, although identified at birth by measurement of the plasma arginine level in siblings of a previously affected patient, generally is not characterized by distinct clinical abnormalities in the newborn period. Acerola cherry is one of the most vitamin c dense foods 4. Mild to absence of hyperammonemia distinguishes arginase deficiency from.
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