A rare autosomal recessive disorder of the urea cycle. It is caused by a deficiency of the hepatic enzyme ARGINASE. Arginine is elevated in the blood and cerebrospinal fluid, and periodic HYPERAMMONEMIA may occur. Disease onset is usually in infancy or early childhood. Clinical manifestations include seizures, microcephaly, progressive mental impairment, hypotonia, ataxia, spastic diplegia, and quadriparesis. (From Hum Genet 1993 Mar;91(1):1-5; Menkes, Textbook of Child Neurology, 5th ed, p51)
A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ornithine (ORNITHINE) and urea. Deficiency of this enzyme causes HYPERARGININEMIA. EC 3.5.3.1.

Generation of a mouse model for arginase II deficiency by targeted disruption of the arginase II gene. (1/26)

Mammals express two isoforms of arginase, designated types I and II. Arginase I is a component of the urea cycle, and inherited defects in arginase I have deleterious consequences in humans. In contrast, the physiologic role of arginase II has not been defined, and no deficiencies in arginase II have been identified in humans. Mice with a disruption in the arginase II gene were created to investigate the role of this enzyme. Homozygous arginase II-deficient mice were viable and apparently indistinguishable from wild-type mice, except for an elevated plasma arginine level which indicates that arginase II plays an important role in arginine homeostasis.  (+info)

Familial hyperargininaemia. (2/26)

A third case of hyperargininaemia occurring in one family was studied from birth. In cord blood serum arginine concentration was only slightly raised, but arginase activity in red blood cell haemolysates was very low. In the urine on day 2 a typical cystinuria pattern was present. Arginine concentration in serum increased to 158 mumol/100 ml on the 41st day of life. Later determinations of the arginase activity in peripheral blood showed values below the sensitivity of the method. Blood ammonia was consistently high, and cystinuria was present. The enzymatic defect was further displayed by intravenous loading tests with arginine. Serum urea values were predominantly normal or near the lower limit of normal, suggesting the presence of other metabolic pathways of urea synthesis. In urine there was no excretion of guanidinosuccinic acid, while the excretion of other monosubstituted guanidine derivatives was increased, pointing to a connexion with hyperargininaemia. Owing to parental attitude, a low protein diet (1-5 g/kg) was introduced only late. The infant developed severe mental retardation, athetosis, and spasticity.  (+info)

Arginase expression in mouse embryonic development. (3/26)

We are using the model of the developing mouse embryo to elucidate the pattern of arginase expression in mammalian cells in normal animals and in arginase I (AI) deficiency during development by digoxigenin-labeled RNA in situ hybridization. Our goal is to understand the regulation of these isozymes, with the expectation that this knowledge will help patients suffering from AI deficiency. We found that AI mRNA was widely and strongly expressed in the normal developing mouse embryo; in contrast, a relatively strong AII mRNA signal was found only in the intestine. In the AI knockout mouse embryo, no AII overexpression was found. These results indicated that arginases are needed in mouse embryonic development and AI is the principal form required. The strong AI expression in the peripheral nervous system suggests that the pathogenesis of the neurological retardation in AI deficiency may be conditioned by AI deficiency in the nervous system during embryonic development.  (+info)

Mouse model for human arginase deficiency. (4/26)

Deficiency of liver arginase (AI) causes hyperargininemia (OMIM 207800), a disorder characterized by progressive mental impairment, growth retardation, and spasticity and punctuated by sometimes fatal episodes of hyperammonemia. We constructed a knockout mouse strain carrying a nonfunctional AI gene by homologous recombination. Arginase AI knockout mice completely lacked liver arginase (AI) activity, exhibited severe symptoms of hyperammonemia, and died between postnatal days 10 and 14. During hyperammonemic crisis, plasma ammonia levels of these mice increased >10-fold compared to those for normal animals. Livers of AI-deficient animals showed hepatocyte abnormalities, including cell swelling and inclusions. Plasma amino acid analysis showed the mean arginine level in knockouts to be approximately fourfold greater than that for the wild type and threefold greater than that for heterozygotes; the mean proline level was approximately one-third and the ornithine level was one-half of the proline and ornithine levels, respectively, for wild-type or heterozygote mice--understandable biochemical consequences of arginase deficiency. Glutamic acid, citrulline, and histidine levels were about 1.5-fold higher than those seen in the phenotypically normal animals. Concentrations of the branched-chain amino acids valine, isoleucine, and leucine were 0.4 to 0.5 times the concentrations seen in phenotypically normal animals. In summary, the AI-deficient mouse duplicates several pathobiological aspects of the human condition and should prove to be a useful model for further study of the disease mechanism(s) and to explore treatment options, such as pharmaceutical administration of sodium phenylbutyrate and/or ornithine and development of gene therapy protocols.  (+info)

Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia. (5/26)

Argininemia is caused by a hereditary deficiency of liver-type arginase (E.C.3.5.3.1) and is characterized by psychomotor retardation and spastic tetraplegia. We examined findings in three Japanese patients with argininemia, by using the PCR, cloning, and sequencing procedures. We found three different mutations--G-to-A-365 in exon 4, G-to-C-703 in exon 7, and C-del-842 in exon 8--thereby leading to mutant arginase proteins of W122X, G235R, and L282FS, respectively. Patient 1 was a compound heterozygote, inheriting the allele with G-to-A-365 from his mother and the allele with G-to-C-703 from his father. Patients 2 and 3 were homozygotes of the allele with G-to-C-703 and of the allele with C-del-842, respectively. Expression tests of these mutant arginases in Escherichia coli indicated that the mutant arginase of W122X did not remain a stable product. The other two mutant arginases--G235R and L282FS--were detected by immunoblot analyses. There was no evidence of activity of the three mutant arginases expressed in E. coli. We tentatively conclude that argininemia is heterogeneous, at the molecular level.  (+info)

Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism. (6/26)

Urea cycle disorders (UCD) are human conditions caused by the dysregulation of nitrogen transfer from ammonia nitrogen into urea. The biochemistry and the genetics of these disorders were well elucidated. Earlier diagnosis and improved treatments led to an emerging, longer-lived cohort of patients. The natural history of some of these disorders began to point to pathophysiological processes that may be unrelated to the primary cause of acute morbidity and mortality, i.e., hyperammonemia. Carbamyl phosphate synthetase I single nucleotide polymorphisms may be associated with altered vascular resistance that becomes clinically relevant when specific environmental stressors are present. Patients with argininosuccinic aciduria due to a deficiency of argininosuccinic acid lyase are uniquely prone to chronic hepatitis, potentially leading to cirrhosis. Moreover, our recent observations suggest that there may be an increased prevalence of essential hypertension. In contrast, hyperargininemia found in patients with arginase 1 deficiency is associated with pyramidal tract findings and spasticity, without significant hyperammonemia. An intriguing potential pathophysiological link is the dysregulation of intracellular arginine availability and its potential effect on nitric oxide (NO) metabolism. By combining detailed natural history studies with the development of tissue-specific null mouse models for urea cycle enzymes and measurement of nitrogen flux through the cycle to urea and NO in UCD patients, we may begin to dissect the contribution of different sources of arginine to NO production and the consequences on both rare genetic and common multifactorial diseases.  (+info)

Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity. (7/26)

The balance of arginine metabolism via nitric oxide synthase (NOS) or arginase is an important determinant of the inflammatory response of murine macrophages and dendritic cells. Here we analyzed the expression of the isoform arginase I in human myeloid cells. Using healthy donors and patients with arginase I deficiency, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of proinflammatory and anti-inflammatory stimuli in vitro. We demonstrate that arginase I is localized in azurophil granules of neutrophils and constitutes a novel antimicrobial effector pathway, likely through arginine depletion in the phagolysosome. Our findings demonstrate important differences between murine and human leukocytes with respect to regulation and function of arginine metabolism via arginase.  (+info)

Molecular genetic study of human arginase deficiency. (8/26)

We have explored the molecular pathology in 28 individuals homozygous or heterozygous for liver arginase deficiency (hyperargininemia) by a combination of Southern analysis, western blotting, DNA sequencing, and PCR. This cohort represents the majority of arginase-deficient individuals worldwide. Only 2 of 15 homozygous patients on whom red blood cells were available had antigenically cross-reacting material as ascertained by western blot analysis using anti-liver arginase antibody. Southern blots of patient genomic DNAs, cut with a variety of restriction enzymes and probed with a near-full-length (1,450-bp) human liver arginase cDNA clone, detected no gross gene deletions. Loss of a TaqI cleavage site was identified in three individuals: in a homozygous state in a Saudi Arabian patient at one site, at a different site in homozygosity in a German patient, and in heterozygosity in a patient from Australia. The changes in the latter two were localized to exon 8, through amplification of this region by PCR and electrophoretic analysis of the amplified fragment after treatment with TaqI; the precise base changes (Arg291X and Thr290Ser) were confirmed by sequencing. It is interesting that the latter nucleotide variant (Thr290Ser) was found to lie adjacent to the TaqI site rather than within it, though whether such a conservative amino acid substitution represents a true pathologic mutation remains to be determined. We conclude that arginase deficiency, though rare, is a heterogeneous disorder at the genotypic level, generally encompassing a variety of point mutations rather than substantial structural gene deletions.  (+info)

Hyperargininemia is a rare genetic disorder characterized by an excess of arginine in the blood. Arginine is an amino acid, which are the building blocks of proteins. In hyperargininemia, there is a deficiency or dysfunction of the enzyme argininosuccinate synthetase, leading to an accumulation of arginine and related compounds in the body. This can cause various symptoms such as intellectual disability, seizures, spasticity, and feeding difficulties. It is inherited in an autosomal recessive manner, meaning that an individual must receive two copies of the defective gene (one from each parent) to develop the condition.

Arginase is an enzyme that plays a role in the metabolism of arginine, an amino acid. It works by breaking down arginine into ornithine and urea. This reaction is part of the urea cycle, which helps to rid the body of excess nitrogen waste produced during the metabolism of proteins. Arginase is found in various tissues throughout the body, including the liver, where it plays a key role in the detoxification of ammonia.

This deficiency is commonly referred to as hyperargininemia or arginemia. The disorder is hereditary and autosomal recessive. ...
Ornithine carbamoyltransferase deficiency Carbamoyl-phosphate synthase I deficiency disease Citrullinemia Hyperargininemia ...
... hyperargininemia MeSH C10.228.140.163.100.375 - hyperglycinemia, nonketotic MeSH C10.228.140.163.100.380 - hyperlysinemias MeSH ...
... hyperargininemia MeSH C18.452.100.100.375 - hyperglycinemia, nonketotic MeSH C18.452.100.100.380 - hyperlysinemias MeSH C18.452 ... hyperargininemia MeSH C18.452.648.151.375 - hyperglycinemia, nonketotic MeSH C18.452.648.151.380 - hyperlysinemias MeSH C18.452 ... hyperargininemia MeSH C18.452.648.066.477 - hyperglycinemia, nonketotic MeSH C18.452.648.066.480 - hyperhomocysteinemia MeSH ...
... hyperargininemia MeSH C16.320.565.150.375 - hyperglycinemia, nonketotic MeSH C16.320.565.150.380 - hyperlysinemias MeSH C16.320 ... hyperargininemia MeSH C16.320.565.066.477 - hyperglycinemia, nonketotic MeSH C16.320.565.066.480 - hyperhomocysteinemia MeSH ...
Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar;84(3):243-51. doi: 10.1016/j.ymgme.2004.11.004. ...
This deficiency is commonly referred to as hyperargininemia or arginemia. The disorder is hereditary and autosomal recessive. ...
Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar. 84(3):243-51. [QxMD MEDLINE Link]. ... Treatment of hyperargininemia with sodium benzoate and arginine- restricted diet. J Pediatr. Mar 1984. 104(3):473-6. [QxMD ... Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase. Mol Genet Metab. ... Scaglia F, Lee B. Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency. Am J Med ...
Crombez, E. A., and Cederbaum, S. D. (2005). Hyperargininemia due to liver arginase deficiency. Mol. Genet. Metab. 84, 243-251 ... These patients reveal urea cycle disorder, hyperargininemia and exhibit neurologically based clinical symptoms in early ...
Learn about diagnosis and specialist referrals for Argininemia.
In both cases, hyperargininemia resolved with repeat testing, suggesting pseudo-hyperargininemia secondary to tPA ... Recent tPA administration can cause pseudo-hyperargininemia and may mimic arginase deficiency or arginine supplementation. JIMD ... who were found to have hyperargininemia (>500 muM; reference 10-140 muM) by plasma amino acid (PAA) analysis of a specimen ... supporting tPA as the cause of pseudo-hyperargininemia. Certain formulations of tPA contain high concentrations of arginine, ...
O Hyperargininemia,O Hyperasparaginemia,O Hyperautofluorescent macular lesion,O Hyperautofluorescent retinal lesion,O ...
Schlune A, Vom Dahl S, Häussinger D, Ensenauer R, Mayatepek E. Hyperargininemia due to arginase I deficiency: the original ...
... including an engineered human arginase for cancer therapy and for treatment of hyperargininemia. ...
HYPERARGININEMIA. HIPERARGININEMIA. HIPERGLICINEMIA NO CETOSICA. HYPERGLYCINEMIA, NONKETOTIC. HIPERGLICINEMIA NÃO-CETÓTICA. ...
HYPERARGININEMIA. HIPERARGININEMIA. HIPERGLICINEMIA NO CETOSICA. HYPERGLYCINEMIA, NONKETOTIC. HIPERGLICINEMIA NÃO-CETÓTICA. ...
HYPERARGININEMIA. HIPERARGININEMIA. HIPERGLICINEMIA NO CETOSICA. HYPERGLYCINEMIA, NONKETOTIC. HIPERGLICINEMIA NÃO-CETÓTICA. ...
HYPERARGININEMIA HIPERARGININEMIA HIPERARGININEMIA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA HIPERGLICINEMIA NÃO- ...
HYPERARGININEMIA HIPERARGININEMIA HIPERARGININEMIA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA HIPERGLICINEMIA NÃO- ...
HYPERARGININEMIA HIPERARGININEMIA HIPERGLICINEMIA NÃO-CETÓTICA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA ...
HYPERARGININEMIA. HIPERARGININEMIA. HIPERGLICINEMIA NO CETOSICA. HYPERGLYCINEMIA, NONKETOTIC. HIPERGLICINEMIA NÃO-CETÓTICA. ...
HYPERARGININEMIA HIPERARGININEMIA HIPERARGININEMIA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA HIPERGLICINEMIA NÃO- ...
HYPERARGININEMIA HIPERARGININEMIA HIPERGLICINEMIA NÃO-CETÓTICA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA ...
HYPERARGININEMIA HIPERARGININEMIA HIPERARGININEMIA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA HIPERGLICINEMIA NÃO- ...
HYPERARGININEMIA HIPERARGININEMIA HIPERARGININEMIA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA HIPERGLICINEMIA NÃO- ...
HYPERARGININEMIA HIPERARGININEMIA HIPERGLICINEMIA NÃO-CETÓTICA HYPERGLYCINEMIA, NONKETOTIC HIPERGLICINEMIA NO CETOSICA ...
Hyperargininemia Hypereosinophilic syndrome (HES) Hyperlipidaemia Hyperphagia Hypersomnia Hypertrophic cardiomyopathy (HCM) ...
Hyperargininemia Hypereosinophilic syndrome (HES) Hyperlipidaemia Hyperphagia Hypersomnia Hypertrophic cardiomyopathy (HCM) ...
Hyperargininemia. Arginase. rare UCD, progressive spastic quadriplegia and mental retardation, ammonia and arginine high in ...
A knowledge graph of biological entities such as genes, gene functions, diseases, phenotypes and chemicals. Embeddings are generated with Walking RDF and OWL method ...
Schuurs-Hoeijmakers, J. H. M., Geraghty, M. T., Kamsteeg, E. J., Ben-Salem, S., De Bot, S. T., Nijhof, B., Van De Vondervoort, I. I. G. M., Van Der Graaf, M., Nobau, A. C., Otte-Höller, I., Vermeer, S., Smith, A. C., Humphreys, P., Schwartzentruber, J., Ali, B. R., Al-Yahyaee, S. A., Tariq, S., Pramathan, T., Bayoumi, R., Kremer, H. P. H., & 20 othersVan De Warrenburg, B. P., Van Den Akker, W. M. R., Gilissen, C., Veltman, J. A., Janssen, I. M., Vulto-Van Silfhout, A. T., Van Der Velde-Visser, S., Lefeber, D. J., Diekstra, A., Erasmus, C. E., Willemsen, M. A., Vissers, L. E. L. M., Lammens, M., Van Bokhoven, H., Brunner, H. G., Wevers, R. A., Schenck, A., Al-Gazali, L., De Vries, B. B. A. & De Brouwer, A. P. M., Dec 7 2012, In: American Journal of Human Genetics. 91, 6, p. 1073-1081 9 p.. Research output: Contribution to journal › Article › peer-review ...
Treatment of hyperargininemia with sodium benzoate and arginine- restricted diet. J Pediatr. Mar 1984. 104(3):473-6. [QxMD ... Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase. Mol Genet Metab. ... Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar. 84(3):243-51. [QxMD MEDLINE Link]. ... Scaglia F, Lee B. Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency. Am J Med ...
Deficiency of this enzyme causes HYPERARGININEMIA. EC 3.5.3.1 1 Liver-Derived Lymphocyte Proliferation Inhibiting Protein -- ...
  • Hyperargininemia due to liver arginase deficiency. (medlineplus.gov)
  • Using directed molecular evolution coupled with high throughput genetic selections and screening strategies, Stone's group has successfully engineered several therapeutic enzyme technologies that are advancing to the clinic, including an engineered human arginase for cancer therapy and for treatment of hyperargininemia. (utexas.edu)