MCID: HYP038
MIFTS: 61

Hyperargininemia malady

Genetic diseases, Rare diseases, Metabolic diseases categories
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Summaries for Hyperargininemia

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NIH Rare Diseases:42 Arginase deficiency is an inherited condition in which the body does not properly process protein in the diet.  individuals with this disease appear healthy at birth, but later develop symptoms between the ages of one and three.  symptoms of arginase deficiency include muscle stiffness (spasticity), decreased growth and intellectual development, and seizures.  arginase deficiency is caused by mutations in the arg1 gene.  treatment may include limiting the amount of protein in the diet, using special dietary formulas that are low in protein, and taking certain medications to remove excess nitrogen from the blood. last updated: 9/13/2012

MalaCards based summary: Hyperargininemia, also known as arginase deficiency, is related to argininosuccinic aciduria and carbamoyl phosphate synthetase i deficiency disease, and has symptoms including speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia, intellectual deficit/mental/psychomotor retardation/learning disability and psychic/behavioural troubles. An important gene associated with Hyperargininemia is ARG1 (arginase 1), and among its related pathways are Alanine and aspartate metabolism and Alanine, aspartate and glutamate metabolism. The compounds Canavaninosuccinate and argininosuccinic acid have been mentioned in the context of this disorder. Affiliated tissues include liver, cortex and brain, and related mouse phenotypes are immune system and behavior/neurological.

Disease Ontology:8 An urea cycle disorder that involves arginase deficiency resulting in elevated levels of plasma arginine.

Genetics Home Reference:21 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. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Wikipedia:65 Argininemia, also called arginase deficiency, is an autosomal recessiveurea cycle disorder where a... more...

Description from OMIM:46 207800

GeneReviews summary for arg1

Aliases & Classifications for Hyperargininemia

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Sources:
8Disease Ontology, 9diseasecard, 19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 62UMLS, 39NCIt, 57SNOMED-CT, 34MeSH, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Hyperargininemia, Aliases & Descriptions:

Name: Hyperargininemia 8 19 42 21 10 44 48 62
Arginase Deficiency 8 19 42 20 22 21 48 62
Argininemia 8 9 42 21 46 48
 
Arginase Deficiency Disease 21 62
Arg1 Deficiency 42 21
Deficiency of Canavanase 8


Classifications:



Characteristics (Orphanet epidemiological data):

48
arginase deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy


External Ids:

Disease Ontology8 DOID:9278
NCIt39 C84568
OMIM46 207800
MeSH34 D020162
SNOMED-CT57 124518006, 23501004
MESH via Orphanet35 D020162
ICD10 via Orphanet26 E72.2
UMLS via Orphanet63 C0268548

Related Diseases for Hyperargininemia

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Graphical network of the top 20 diseases related to Hyperargininemia:



Diseases related to hyperargininemia

Symptoms for Hyperargininemia

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Symptoms by clinical synopsis from OMIM:

207800

Clinical features from OMIM:

207800

Symptoms:

48 (show all 9)
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • psychic/behavioural troubles
  • aminoacid metabolism anomalies/aminoaciduria
  • autosomal recessive inheritance
  • eeg anomalies
  • hemiplegia/diplegia/hemiparesia/limb palsy
  • seizures/epilepsy/absences/spasms/status epilepticus
  • hyperammonemia

HPO human phenotypes related to Hyperargininemia:

(show all 21)
id Description Frequency HPO Source Accession
1 behavioral abnormality hallmark (90%) HP:0000708
2 neurological speech impairment hallmark (90%) HP:0002167
3 aminoaciduria hallmark (90%) HP:0003355
4 cognitive impairment hallmark (90%) HP:0100543
5 seizures typical (50%) HP:0001250
6 hyperammonemia typical (50%) HP:0001987
7 eeg abnormality typical (50%) HP:0002353
8 hemiplegia/hemiparesis typical (50%) HP:0004374
9 autosomal recessive inheritance HP:0000007
10 irritability HP:0000737
11 hyperactivity HP:0000752
12 intellectual disability HP:0001249
13 seizures HP:0001250
14 global developmental delay HP:0001263
15 hyperammonemia HP:0001987
16 vomiting HP:0002013
17 anorexia HP:0002039
18 progressive spastic quadriplegia HP:0002478
19 oroticaciduria HP:0003218
20 diaminoaciduria HP:0008339
21 postnatal growth retardation HP:0008897

Drugs & Therapeutics for Hyperargininemia

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Drug clinical trials:

Search ClinicalTrials for Hyperargininemia

Search NIH Clinical Center for Hyperargininemia

Genetic Tests for Hyperargininemia

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Genetic tests related to Hyperargininemia:

id Genetic test Affiliating Genes
1 Arginase Deficiency20 22 ARG1

Anatomical Context for Hyperargininemia

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MalaCards organs/tissues related to Hyperargininemia:

32
Liver, Cortex, Brain, Skin, Testes

Animal Models for Hyperargininemia or affiliated genes

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MGI Mouse Phenotypes related to Hyperargininemia:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053878.5ARG1, OTC, ASL, ASS1
2MP:00053868.1NACC1, ASS1, ASL, OTC
3MP:00107687.8ARG1, NACC1, ASS1, ASL, OTC
4MP:00053767.1ASS1, NACC1, ASL, OTC, ARG1, ARG2

Publications for Hyperargininemia

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Articles related to Hyperargininemia:

(show all 49)
idTitleAuthorsYear
1
Myocyte-mediated arginase expression controls hyperargininemia but not hyperammonemia in arginase-deficient mice. (24888478)
2014
2
Hyperargininemia: 7-month follow-up under sodium benzoate therapy in an Italian child presenting progressive spastic paraparesis, cognitive decline, and novel mutation in ARG1 gene. (24997092)
2014
3
Effect of N-acetylarginine, a metabolite accumulated in hyperargininemia, on parameters of oxidative stress in rats: protective role of vitamins and L-NAME. (25042906)
2014
4
Novel complex re-arrangement of ARG1 commonly shared by unrelated patients with hyperargininemia. (24103480)
2014
5
Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism. (24224027)
2013
6
Hyperargininemia: a family with a novel mutation in an unexpected site. (23430921)
2012
7
Brain MRI and Magnetic Resonance Spectroscopy Findings in Patients with Hyperargininemia. (22928720)
2012
8
Clinical features and neurologic progression of hyperargininemia. (22633632)
2012
9
Analysis of novel ARG1 mutations causing hyperargininemia and correlation with arginase I activity in erythrocytes. (22959135)
2012
10
Neonatal cholestasis: an uncommon presentation of hyperargininemia. (21229317)
2010
11
Neuroimaging findings in hyperargininemia. (18321250)
2008
12
Increased plasma and tissue guanidino compounds in a mouse model of hyperargininemia. (17997338)
2008
13
NTPDase and 5'-nucleotidase activities of synaptosomes from hippocampus of rats subjected to hyperargininemia. (17401661)
2007
14
Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency. (16602094)
2006
15
L-NAME administration prevents the inhibition of nucleotide hydrolysis by rat blood serum subjected to hyperargininemia. (15977041)
2005
16
Hyperargininemia due to liver arginase deficiency. (15694174)
2005
17
Functional consequences of the G235R mutation in liver arginase leading to hyperargininemia. (11883902)
2002
18
In vitro stimulation of oxidative stress in cerebral cortex of rats by the guanidino compounds accumulating in hyperargininemia. (11743972)
2001
19
In vitro inhibition of Na+,K(+)-ATPase activity from rat cerebral cortex by guanidino compounds accumulating in hyperargininemia. (10446319)
1999
20
Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase. (9758714)
1998
21
Hyperargininemia presenting as persistent neonatal jaundice and hepatic cirrhosis. (9106111)
1997
22
Identification of mutations (D128G, H141L) in the liver arginase gene of patients with hyperargininemia. (7981719)
1994
23
The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and guanidinosuccinic acid. (1518417)
1992
24
Guanidino compounds that are increased in hyperargininemia inhibit GABA and glycine responses on mouse neurons in cell culture. (1712285)
1991
25
Hyperargininemia: intellectual and motor improvement related to changes in biochemical data. (1999785)
1991
26
Absence of erythrocyte arginase protein in Japanese patients with hyperargininemia. (1959545)
1991
27
Guanidino compound analysis as a complementary diagnostic parameter for hyperargininemia: follow-up of guanidino compound levels during therapy. (1690873)
1990
28
Hyperargininemia, epilepsy and the metabolism of guanidino compounds. (2657590)
1989
29
Differential expression of the two human arginase genes in hyperargininemia. Enzymatic, pathologic, and molecular analysis. (2913054)
1989
30
Guanidino compounds in hyperargininemia. (3433275)
1987
31
Enzyme replacement therapy in a patient with hyperargininemia. (3590176)
1987
32
Treatment of hyperargininemia with sodium benzoate and arginine-restricted diet. (6707802)
1984
33
Hyperargininemia: the rat as a model for the human disease and the comparative response to enzyme replacement therapy with free arginase and arginase-loaded erythrocytes in vivo. (6468738)
1984
34
Hyperargininemia: effect of ornithine and lysine supplementation. (6415261)
1983
35
Isoenzyme pattern and immunological properties of arginase in normal and hyperargininemia fibroblasts. (6404622)
1983
36
Hyperargininemia: clinical course and treatment with sodium benzoate and phenylacetic acid. (6670711)
1983
37
Measurement of arginine transport in human erythrocytes using their intrinsic arginase activity: implications for the treatment of familial hyperargininemia. (6817948)
1982
38
Guanidino compounds in hyperargininemia. (7164915)
1982
39
Ammonia metabolism in a family affected by hyperargininemia. (7238975)
1981
40
Excretion of alpha-keto-delta-guanidinovaleric acid and its cyclic form in patients with hyperargininemia. (498528)
1979
41
Arginase and free amino acids in hyperargininemia: leukocyte arginine as a diagnostic parameter for heterozygotes. (438730)
1979
42
Hyperargininemia with arginase deficiency. (481955)
1979
43
Human hyperargininemia: a mutation not expressed in skin fibroblasts? (879168)
1977
44
A simple screening test for arginase deficiency (hyperargininemia). (845487)
1977
45
Lysine supplementation in hyperargininemia. (925806)
1977
46
Hyperargininemia. (839368)
1977
47
Use of enzyme-loaded erythrocytes in in-vitro correction of arginase-deficient erythrocytes in familial hyperargininemia. (1253407)
1976
48
Further investigations in hyperargininemia. (4663887)
1972
49
Familial hyperargininemia. (4643877)
1972

Variations for Hyperargininemia

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UniProtKB/Swiss-Prot genetic disease variations for Hyperargininemia:

64
id Symbol AA change Variation ID SNP ID
1ARG1p.Gly235ArgVAR_000674
2ARG1p.Ile11ThrVAR_015594rs28941474
3ARG1p.Gly138ValVAR_015595

Clinvar genetic disease variations for Hyperargininemia:

6 (show all 12)
id Gene Name Type Significance SNP ID Assembly Location
1ARG1ARG1, 4-BP DELdeletionPathogenic
2ARG1ARG1, 1-BP DELdeletionPathogenic
3NM_000045.3(ARG1): c.871C> T (p.Arg291Ter)single nucleotide variantPathogenicrs104893940GRCh37Chr 6, 131904950: 131904950
4NM_000045.3(ARG1): c.869C> G (p.Thr290Ser)single nucleotide variantPathogenicrs104893942GRCh37Chr 6, 131904948: 131904948
5NM_000045.3(ARG1): c.365G> A (p.Trp122Ter)single nucleotide variantPathogenicrs104893947GRCh37Chr 6, 131902418: 131902418
6NM_000045.3(ARG1): c.703G> C (p.Gly235Arg)single nucleotide variantPathogenicrs104893948GRCh37Chr 6, 131904532: 131904532
7ARG1ARG1, 1-BP DEL, 842CdeletionPathogenic
8ARG1NM_000045.3(ARG1): c.32T> C (p.Ile11Thr)single nucleotide variantPathogenicrs28941474GRCh37Chr 6, 131894454: 131894454
9NM_000045.3(ARG1): c.413G> T (p.Gly138Val)single nucleotide variantPathogenicrs104893943GRCh37Chr 6, 131902466: 131902466
10ARG1NM_000045.3(ARG1): c.57+1G> Asingle nucleotide variantPathogenicGRCh37Chr 6, 131894480: 131894480
11ARG1ARG1, IVS4, A-G, -2single nucleotide variantPathogenic
12NM_000045.3(ARG1): c.61C> T (p.Arg21Ter)single nucleotide variantPathogenicrs104893944GRCh37Chr 6, 131897806: 131897806

Expression for genes affiliated with Hyperargininemia

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Expression patterns in normal tissues for genes affiliated with Hyperargininemia

Search GEO for disease gene expression data for Hyperargininemia.

Pathways for genes affiliated with Hyperargininemia

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Pathways related to Hyperargininemia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.5ASL, ASS1
29.5ASS1, ASL
39.2ARG2, ARG1
4
Show member pathways
glutamate biosynthesis II37
arginine biosynthesis IV37
8.9ASS1, ASL, OTC
5
Show member pathways
citrulline-nitric oxide cycle37
arginine degradation I (arginase pathway)37
proline degradation37
glutamine degradation I37
proline biosynthesis I37
superpathway of citrulline metabolism37
proline biosynthesis II (from arginine)37
citrulline biosynthesis37
arginine degradation VI (arginase 2 pathway)37
Urea cycle and metabolism of amino groups37
asparagine biosynthesis I37
4-hydroxyproline degradation I37
citrulline degradation37
7.6ARG1, ASS1, ASL, OTC, ARG2
6
Show member pathways
L-serine degradation37
pentose phosphate pathway (oxidative branch)37
formaldehyde oxidation II (glutathione-dependent)37
7.6ARG1, OTC, ARG2, ASL, ASS1
7
Show member pathways
7.6ARG2, OTC, ARG1, ASS1, ASL
8
Show member pathways
creatine-phosphate biosynthesis37
glycine degradation (creatine biosynthesis)37
putrescine biosynthesis III37
spermidine biosynthesis I37
tryptophan degradation via kynurenine37
spermine biosynthesis37
urea cycle37
S-methyl-5-thio-alpha-D-ribose 1-phosphate degradation I37
tyrosine degradation I37
L-carnitine biosynthesis37
methylthiopropionate biosynthesis37
2-oxoglutarate decarboxylation to succinyl-CoA37
S-methyl-5-thioadenosine degradation II37
7.6ASL, OTC, ARG2, ARG1, ASS1

Compounds for genes affiliated with Hyperargininemia

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Sources:
24HMDB, 44Novoseek, 50PharmGKB, 28IUPHAR, 11DrugBank, 2BitterDB
See all sources

Compounds related to Hyperargininemia according to GeneCards/GeneDecks:

(show all 30)
idCompoundScoreTop Affiliating Genes
1Canavaninosuccinate249.8ASL, ASS1
2argininosuccinic acid44 2410.8ASL, ASS1
3guanidinoacetate449.7ASS1, ASL
4n-acetylglutamate449.7ASL, OTC
5sodium phenylbutyrate509.6ASS1, OTC
6putrescine44 28 24 1112.6ARG1, OTC
72(s)-amino-6-boronohexanoic acid44 1110.6ARG2, ARG1
8s-2-(boronoethyl)-l-cysteine44 1110.5ARG2, ARG1
9delta(1)pyrroline-5-carboxylate449.5ASS1, OTC
10l-citrulline28 1110.5OTC, ASS1
11malate449.5ASL, OTC
12phosphoenolpyruvate44 1110.3OTC, ASS1
13manganese44 2410.2ARG1, ARG2
14ammonium449.2OTC, ASL, ASS1
15pyruvate449.0OTC, ASS1
16l-ornithine28 1110.0ARG1, ARG2, OTC
17proline448.9ARG1, ASL, ARG2
18sodium benzoate50 29.9OTC, ASL, ASS1, ARG1
19phenylacetic acid50 44 2410.9ASS1, ASL, OTC, ARG1
20carbamoyl phosphate448.8OTC, ASL, ARG1, ASS1
21citrulline44 249.8ASL, ASS1, ARG1, OTC
22atp44 289.8ASS1, OTC, ARG1
23aspartate448.7ASL, OTC, ASS1, ARG1
24l-arginine28 24 1110.6ARG2, ASL, ASS1, ARG1
25creatinine448.3OTC, ASL, ARG2, ASS1
26ornithine44 249.0ASL, ARG1, ASS1, ARG2, OTC
27urea44 24 1110.0ASS1, ARG2, OTC, ASL, ARG1
28arginine448.0ARG1, ASS1, ASL, OTC, ARG2
29nitric oxide44 24 1110.0ASS1, ARG1, ARG2, OTC, ASL
30glutamate448.0ARG1, ARG2, ASL, ASS1, OTC

GO Terms for genes affiliated with Hyperargininemia

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Biological processes related to Hyperargininemia according to GeneCards/GeneDecks:

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1arginine catabolic processGO:0065279.6ARG1, ASL
2arginine biosynthetic processGO:0065269.4ASS1, OTC
3liver developmentGO:0018899.4OTC, ARG1
4protein homotrimerizationGO:0702079.3ARG1, OTC
5response to zinc ionGO:0100439.1ARG1, OTC
6urea cycleGO:0000507.8ARG1, ARG2, OTC, ASL, ASS1
7cellular nitrogen compound metabolic processGO:0346417.8ARG2, OTC, ASL, ASS1, ARG1
8small molecule metabolic processGO:0442817.7ARG1, OTC, ASL, ARG2, ASS1

Products for genes affiliated with Hyperargininemia

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  • Antibodies
  • Proteins
  • Lysates

Sources for Hyperargininemia

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet