Humans express two distinct arginase genes identified as arg1 and arg2 that encode the arginase type i and type ii enzymes, respectively. Arginase deficiency argininemia is an autosomal recessive metabolic. Ornithine deficiency in the arginase double knockout mouse. Arginase deficiency genetic and rare diseases information.
Arginase deficiency ad is inherited as an autosomal recessive disorder resulting from mutations in the arginase gene. Patients with arg1 deficiency typically present later in life with spasticity, seizures and failure to thrive. Arginase1 arg1 deficiency is a rare autosomal recessive disorder that affects the liverbased urea cycle, leading to impaired ureagenesis. Obetadglucopyranoside pg, inhibits arginase activity. The arginase 1 deficiency facebook page is a community where you can learn more information about arginase 1 deficiency and connect with. Its deficiency is the least frequently described disorder of this cycle. It results from the absence of the enzyme arginase 1, which breaks down arginine to ornithine and urea, leading to episodic hyperammonemia. 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.
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 activity assay kit mak112 technical bulletin. This enzymes job is to help break down the amino acid arginine and to help remove ammonia from the body when arginase is not working, arginine, along with. Arginase deficiency occurs when an enzyme called arginase is either missing or not working properly. Arginase catalyzes the conversion of arginine to ornithine and urea, completing the last step in the urea cycle. 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. Overview arginase deficiency is the least common of the urea cycle disorders. Because the nervous system is especially sensitive to the effects of excess ammonia, argininemia causes spasticity, developmental delay, intellectual disability, seizures, tremor, and ataxia. These children inherit one nonworking arg1 gene for the condition from each parent. Apr 25, 2017 arginase deficiency is inherited in an autosomal recessive manner.
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. Pdf arginase 1 arg1 deficiency is a rare autosomal recessive disorder that affects the liverbased urea cycle, leading to impaired ureagenesis. In a japanese girl with argininemia, haraguchi et al. Arginase deficiency argininemia statpearls ncbi bookshelf. Pdf arginase1 arg1 deficiency is a rare autosomal recessive disorder that. Mutations in arg1 gene are rare and the frequency of ad is approximately 1 per 363,000 live births. Arginase enzyme has an advantage when there is tetrahydorbiopterin bh4 deficiency or arginine deficiency. Recombinant human arginase 1arg1 protein, cf 5868ar010. 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. Argininemia also known as arginase deficiency is an inherited disorder that causes arginine and ammonia to accumulate gradually in the blood. Michels and beaudet 1978 reported an affected mexican child with growth retardation, microcephaly, mental retardation, spasticity, and epileptiform discharges on eeg. 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. Many physiologic and pathophysiologic processes are modulated by arginine availability, which can be regulated by arginase.
Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. Jul 02, 2015 a phase 12 openlabel study in patients with arginase i deficiency to investigate the safety, pharmacokinetics, and pharmacodynamics of intravenous aeb1102. The human arginases and arginase deficiency springerlink. Arginase deficiencyhyperargininaemia argininemia argininosuccinic acidemia asa lyase deficiency carbamoyl phosphate synthetase deficiency citrullinemia asa synthetase deficiency glutaric acidemiaaciduria glutathione synthetase deficiency 5oxoprolinuria homocystinuria cystathione synthase deficiency hypermethioninemia. An enzyme found primarily in the liver that catalyzes the hydrolysis of arginine to form urea and ornithine. Parents of children with arginase deficiency rarely have the condition themselves. 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. The primary endpoint of the trial is safety and tolerability of intravenous administration of aeb1102 in. The disorder is hereditary and autosomal recessive. If the arginase enzyme is misshapen or missing, it cannot fulfill its role in the urea cycle. Human recombinant arginase enzyme reduces plasma arginine.
This is one of a small number of amino acid disorders called urea cycle disordersucd. This deficiency is commonly referred to as hyperargininemia or arginemia. Arginase is a target for treating cardiovascular disease. Arginase is the mediator of the terminal step in the urea cycle, explaining the relatively mild clinical. Arginase deficiency definition of arginase deficiency by. 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. Pdf arginase1 arg1 deficiency is a rare autosomal recessive disorder that affects the liverbased urea cycle, leading to impaired ureagenesis. Arginase deficiency is an inherited metabolic disease in which the body is unable to process arginine a building block of protein. A phase 12 study of aeb1102 in patients with arginase i. Although a catastrophic neonatal presentation is very uncommon in arginase deficiency, dietary protein intolerance is an early sign and should not be overlooked. 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. Jan 07, 2019 diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Join the arginase deficiency argininemia community.
Arginase deficiency hyperargininaemia argininemia argininosuccinic acidemia asa lyase deficiency carbamoyl phosphate synthetase deficiency citrullinemia asa synthetase deficiency glutaric acidemiaaciduria glutathione synthetase deficiency 5oxoprolinuria homocystinuria cystathione synthase deficiency hypermethioninemia. World map of arginase deficiencyargininemia find people with arginase deficiencyargininemia through the map. Arginase i arg1 deficiency, a rare autosomal recessive disorder of ureagenesis has classically been the phenotypic exception within urea cycle disorders. Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. 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. Disorders of arginine metabolism are included in a larger group of. Hyperargininemia due to arginase deficiency is an inherited autosomal recessive disease. 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. Arginase deficiency also called argininemia argininosuccinic aciduria biopterin cofactor defects citrullinemia, type i citrullienemia, type ii also called citron deficiency hypermethioninenemia hyperphenylalaninemia also called hphe maple syrup urine disease also called msud. The arginase enzyme developed in early life forms and was maintained during evolution. Oct 14, 2015 arginase 1 arg1 deficiency is a rare autosomal recessive disorder that affects the liverbased urea cycle, leading to impaired ureagenesis. The distinct tendency to develop spastic diplegia in patients with arginase deficiency, as compared with patients with other urea cycle disorders, suggests a specific pathogenic mechanism at the cns level, apart from the generalized toxicity of hyperammonemia. This appears to be due to a second arginase locus, expressed primarily in the kidney, which can be recruited to compensate, in part, for the. Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling.
Aeglea biotherapeutics doses first patients in phase 1 trial. Rescue of the functional alterations of motor cortical circuits in arginase deficiency by neonatal gene therapy. Arginase deficiency disorder is a rare inherited condition characterized by an insufficient level or complete lack of an important enzyme known as arginase. 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. In recent years, evidence has accumulated indicating that the enzyme arginase, which converts larginine into lornithine and urea, plays a key role in the pathogenesis of pulmonary disorders such as asthma through dysregulation of larginine metabolism and modulation of nitric oxide no homeostasis. Human recombinant arginase enzyme reduces plasma arginine in. It belongs to a group of disorders known as urea cycle disorders.
Facebook is showing information to help you better understand the purpose of a page. Increased synthesis of spermidine as a result of upregulation of arginase i promotes axonal regeneration in culture and in vivo. Ucdc healthcare professionals disorder definitions. Icd10 code of arginase deficiencyargininemia and icd9 code. Inherited disorder that causes arginine amino acid and ammonia to build up in the blood. This is a case report of a 9year old girl presenting with. Arginase deficiency is one of the least frequent of the urea cycle disorders with an incidence between 1. Arginase 1, also known as liver arginase, is a binuclear manganese metalloenzyme. Pdf hyperargininemia due to arginase deficiency is a rare, inherited, urea cycle disorder.
In a study of 20 persons homozygous or heterozygous for arginase deficiency, grody et al. Arginase deficiency hyperargininemia arginase is the sixth and final enzyme of the urea cycle and converts arginine to urea and ornithine. This is a case report of a 9year old girl presenting. It results primarily in elevated blood arginine, and less frequently in either persistent or acute elevations in blood ammonia. The parents of a person with arginase deficiency usually each carry one mutated copy of the gene and are referred to as carriers. The urea cycle provides protection against excess ammonia, while lornithine is needed for cell proliferation, collagen formation, and other physiological functions. 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.
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. The primary endpoint of the trial is safety and tolerability of intravenous administration of aeb1102 in patients with arginase i deficiency. Aeglea biotherapeutics doses first patients in phase 1. For language access assistance, contact the ncats public information officer. The shape of an enzyme affects its ability to control a chemical reaction. Hepatic arginase deficiency fosters dysmyelination during. If you have problems viewing pdf files, download the latest version of adobe reader.
We would like to show you a description here but the site wont allow us. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. Urea is excreted from the body, and ornithine is recycled. In children with arginase deficiency, neither of these genes works correctly.
Arginase deficiency can lead to severe symptoms including neurological impairment, dementia and hyperammonemia. A deficiency, usually near complete absence, of activity of arginase, blocks the final step of the cycle. A block in this enzyme activity results in high levels of arginine. Arginase1 deficiency nord national organization for. The nervous system is especially sensitive to the effects of excess ammonia. Mutations in arg1 give rise to hyperargininemia also known as arginase deficiency ad. Two isoforms of arginase are present in most mammals, which differ in their tissue distribution and subcellular localization. These occur when the bodys process for removing ammonia is disrupted, which can cause ammonia levels in the blood to rise hyperammonemia.
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. Characteristic phenotypic features of arginase deficiency include spastic diplegia, seizures, intellectual disability ranging from mild to severe, selfprotein restriction and growth deficiency 1, 2. Arginase deficiency is the most uncommon urea cycle disorder. Aug 26, 2014 argininemia also known as arginase deficiency is an inherited disorder that causes arginine and ammonia to accumulate gradually in the blood. Arginase definition of arginase by the free dictionary. Increased levels of arginase activity in blood have been associated with liver damage. Infection with arginasedeficient leishmania major reveals a. It is characterized by lowered activity of arginase in hepatic cells. The lack of the arginase enzyme results in excessive.
Cederbaum, in neurology and clinical neuroscience, 2007. A phase 12 openlabel study in patients with arginase i deficiency to investigate the safety, pharmacokinetics, and pharmacodynamics of intravenous aeb1102. Pathogenesis host cellular arginase activity and disease and. Most commonly, birth and early childhood are normal. 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. Enable javascript to view the expandcollapse boxes. Instead, each parent has a single nonworking gene for arginase deficiency. Jan 07, 2019 arginase deficiency is thought to be the least common of the urea cycle disorders.
Argininemia as a cause of severe chronic stunting and partia. The code is valid for the year 2020 for the submission of hipaacovered transactions. 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. 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 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. 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. Arginase deficiency is typically not characterized by severe increase in ammonia. World map of arginase deficiency argininemia find people with arginase deficiency argininemia through the map. This entity also manifests itself in a fashion somewhat different from other disorders in the group see physical. Arginase deficiency in multiple tissues in argininemia. Arginase1 deficiency nord national organization for rare. What is the life expectancy of someone with arginase. Deng k, he h, qiu j, lorber b, bryson jb, filbin mt. Argininemia is an autosomal recessive inherited disorder of the urea cycle. Cantero g, liu xb, mervis rf, lazaro mt, cederbaum sd, golshani p, et al. 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 nature of this mechanism remains unelucidated, but some workers have pointed to an accumulation of guanidino compounds.
Arginase i is mainly present in the liver and plays an important part in the urea cycle whereas arginase ii is present in kidney and other tissues and regulates arginineornithine concentration. Argininemia arginase deficiency, hyperargininemia what are the characteristics of argininemia. This means that to be affected, a person must have a diseasecausing mutation in both copies of the gene associated with arginase deficiency. Arginase definition of arginase by medical dictionary. Ammonia, which is formed when proteins are broken down in the body, is. Two separate isozymes of the enzyme arginase have been reported. Because of its atypical symptoms in early age, diagnosis can be delayed until the.
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