MCID: ARG007
MIFTS: 51

Argininemia

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Argininemia

MalaCards integrated aliases for Argininemia:

Name: Argininemia 53 12 49 24 55 71 13
Hyperargininemia 53 12 23 49 24 55 71 36 51 41 14 69
Arginase Deficiency 53 12 72 23 49 24 55 71 28
Arg1 Deficiency 53 49 24 71
Arginase Deficiency Disease 24
Deficiency of Canavanase 12
Arginase-1 Deficiency 71
Argin 71

Characteristics:

Orphanet epidemiological data:

55
argininemia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: Childhood,Infancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
prevalence is estimated to be 1 in 1,100,000


HPO:

31
argininemia:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Inborn errors of metabolism


External Ids:

OMIM 53 207800
Disease Ontology 12 DOID:9278
ICD10 32 E72.21
MeSH 41 D020162
NCIt 46 C84568
SNOMED-CT 64 124518006 23501004
Orphanet 55 ORPHA90
MESH via Orphanet 42 D020162
UMLS via Orphanet 70 C0268548
ICD10 via Orphanet 33 E72.2
MedGen 39 C0268548
KEGG 36 H00186
UMLS 69 C0268548

Summaries for Argininemia

NIH Rare Diseases : 49 Arginase deficiency is an inheritedmetabolic disease in which the body is unable to process arginine (a building block of protein). It belongs to a group of disorders known as urea cycle disorders. These occur when the body's process for removing ammonia is disrupted, which can cause ammonia levels in the blood to rise (hyperammonemia). In most cases, symptoms appear between the ages of one and three years. Symptoms may include feeding problems, vomiting, poor growth, seizures, and stiff muscles with increased reflexes (spasticity). People with arginase deficiency may also have developmental delay, loss of developmental milestones, and intellectual disability. Arginase deficiency is caused by mutations in the ARG1 gene and is inherited in an autosomal recessive manner. Treatment is focused on lowering arginine levels and preventing hyperammonemia. People with arginase deficiency are generally placed on a very low-protein diet with the help of a registered metabolic dietitian. They may be prescribed certain medications called nitrogen-scavenging drugs. Last updated: 4/25/2017

MalaCards based summary : Argininemia, also known as hyperargininemia, is related to argininosuccinic aciduria and carbamoyl phosphate synthetase i deficiency, hyperammonemia due to, and has symptoms including seizures, neurological speech impairment and eeg abnormality. An important gene associated with Argininemia is ARG1 (Arginase 1), and among its related pathways/superpathways are Arginine biosynthesis and Arginine and proline metabolism. The drug Vaccines has been mentioned in the context of this disorder. Affiliated tissues include liver and brain, and related phenotypes are homeostasis/metabolism and integument

Disease Ontology : 12 An urea cycle disorder that involves arginase deficiency resulting in elevated levels of plasma arginine.

Genetics Home Reference : 24 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.

OMIM : 53 Arginase deficiency is an autosomal recessive inborn error of metabolism caused by a defect in the final step in the urea cycle, the hydrolysis of arginine to urea and ornithine. Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: ornithine transcarbamylase deficiency (311250), carbamyl phosphate synthetase deficiency (237300), argininosuccinate synthetase deficiency, or citrullinemia (215700), argininosuccinate lyase deficiency (207900), and arginase deficiency. (207800)

UniProtKB/Swiss-Prot : 71 Argininemia: A rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia and progressive spastic quadriplegia.

Wikipedia : 72 Argininemia, also called arginase deficiency, is an autosomal recessive urea cycle disorder where a... more...

GeneReviews: NBK1159

Related Diseases for Argininemia

Graphical network of the top 20 diseases related to Argininemia:



Diseases related to Argininemia

Symptoms & Phenotypes for Argininemia

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
progressive spastic quadriplegia
developmental delay
mental retardation

Neurologic Behavioral Psychiatric Manifestations:
irritability
hyperactivity

Growth Other:
growth failure

Abdomen External Features:
vomiting
anorexia

Laboratory Abnormalities:
hyperammonemia
hyperarginemia
diaminoaciduria (arginuria, lysinuria, cystinuria, ornithinuria)
orotic aciduria
pyrimidinuria
more
Metabolic Features:
protein intolerance


Clinical features from OMIM:

207800

Human phenotypes related to Argininemia:

55 31 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 frequent (33%) Frequent (79-30%) HP:0001250
2 neurological speech impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0002167
3 eeg abnormality 55 31 frequent (33%) Frequent (79-30%) HP:0002353
4 behavioral abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0000708
5 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
6 intellectual disability, severe 55 31 hallmark (90%) Very frequent (99-80%) HP:0010864
7 hemiplegia/hemiparesis 55 31 frequent (33%) Frequent (79-30%) HP:0004374
8 hyperammonemia 55 31 frequent (33%) Frequent (79-30%) HP:0001987
9 progressive spastic quadriplegia 55 31 frequent (33%) Frequent (79-30%) HP:0002478
10 diaminoaciduria 55 31 hallmark (90%) Very frequent (99-80%) HP:0008339
11 vomiting 31 HP:0002013
12 intellectual disability 31 HP:0001249
13 irritability 31 HP:0000737
14 postnatal growth retardation 31 HP:0008897
15 anorexia 31 HP:0002039
16 hyperactivity 31 HP:0000752
17 oroticaciduria 31 HP:0003218

UMLS symptoms related to Argininemia:


vomiting, seizures

MGI Mouse Phenotypes related to Argininemia:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.63 ARG1 ASL ASS1 CPS1 NAGS OTC
2 integument MP:0010771 9.26 ASL ASS1 NAGS OTC
3 mortality/aging MP:0010768 9.1 ARG1 ASL ASS1 CPS1 NAGS OTC

Drugs & Therapeutics for Argininemia

Drugs for Argininemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Vaccines

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 1/2 Study of AEB1102 in Patients With Arginase I Deficiency Recruiting NCT02488044 Phase 1, Phase 2 AEB1102
2 A Study of AEB1102 (Pegzilarginase) in Patients With Arginase I Deficiency Recruiting NCT03378531 Phase 2 AEB1102
3 The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity Terminated NCT01421888

Search NIH Clinical Center for Argininemia

Cochrane evidence based reviews: hyperargininemia

Genetic Tests for Argininemia

Genetic tests related to Argininemia:

# Genetic test Affiliating Genes
1 Arginase Deficiency 28 ARG1

Anatomical Context for Argininemia

MalaCards organs/tissues related to Argininemia:

38
Liver, Brain

Publications for Argininemia

Articles related to Argininemia:

(show all 34)
# Title Authors Year
1
Argininemia as a cause of severe chronic stunting and partial growth hormone deficiency (PGHD): A case report. ( 29443755 )
2018
2
Three novel mutations of ARG1 identified in Chinese patients with argininemia detected by newborn screening. ( 28089752 )
2017
3
Argininemia as a cause of severe chronic stunting in a low-resource developing country setting: a case report. ( 27549856 )
2016
4
Argininemia and plasma arginine bioavailability - predictive factors of mortality in the severe trauma patients? ( 27582779 )
2016
5
Myocyte-mediated arginase expression controls hyperargininemia but not hyperammonemia in arginase-deficient mice. ( 24888478 )
2014
6
Case Report of Argininemia: The Utility of the Arginine/Ornithine Ratio for Newborn Screening (NBS). ( 23430558 )
2013
7
Liver transplantation prevents progressive neurological impairment in argininemia. ( 23559324 )
2013
8
Five novel mutations in ARG1 gene in Chinese patients of argininemia. ( 23859858 )
2013
9
Epilepsia Partialis Continua and Generalized Nonconvulsive Status Epilepticus during the Course of Argininemia: A Report on Two Cases. ( 24258525 )
2013
10
Argininemia presenting with progressive spastic diplegia. ( 21310339 )
2011
11
Guanidino compound levels in blood, cerebrospinal fluid, and post-mortem brain material of patients with argininemia. ( 20176499 )
2010
12
Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. ( 20004862 )
2010
13
A novel mutation in ARG1 gene is responsible for arginase deficiency in an Asian family. ( 19936428 )
2009
14
Hyperargininemia due to liver arginase deficiency. ( 15694174 )
2005
15
Prenatal diagnosis for arginase deficiency by second-trimester fetal erythrocyte arginase assay and first-trimester ARG1 mutation analysis. ( 15565656 )
2004
16
Identification of a novel R21X mutation in the liver-type arginase gene (ARG1) in four Portuguese patients with argininemia. ( 10502833 )
1999
17
The human arginases and arginase deficiency. ( 9686347 )
1998
18
Argininemia: a treatable genetic cause of progressive spastic diplegia simulating cerebral palsy: case reports and literature review. ( 9378897 )
1997
19
Molecular basis of phenotypic variation in patients with argininemia. ( 7649538 )
1995
20
Arginase deficiency manifesting delayed clinical sequelae and induction of a kidney arginase isozyme. ( 8454280 )
1993
21
Arginase Deficiency ( 20301338 )
1993
22
Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia. ( 1463019 )
1992
23
Molecular genetic study of human arginase deficiency. ( 1598908 )
1992
24
Molecular basis of argininemia. Identification of two discrete frame-shift deletions in the liver-type arginase gene. ( 2365823 )
1990
25
Argininemia. ( 2638334 )
1989
26
A successful trial of enzyme replacement therapy in a case of argininemia. ( 6729810 )
1984
27
Argininemia: report of a new case and mechanisms of orotic aciduria and hyperammonemia. ( 7164892 )
1982
28
Clinical and biochemical findings in argininemia. ( 7164891 )
1982
29
Argininemia treated from birth. ( 480013 )
1979
30
Hyperargininemia with arginase deficiency. ( 481955 )
1979
31
Arginase deficiency in multiple tissues in argininemia. ( 624188 )
1978
32
A simple screening test for arginase deficiency (hyperargininemia). ( 845487 )
1977
33
Argininemia. ( 839367 )
1977
34
Use of enzyme-loaded erythrocytes in in-vitro correction of arginase-deficient erythrocytes in familial hyperargininemia. ( 1253407 )
1976

Variations for Argininemia

UniProtKB/Swiss-Prot genetic disease variations for Argininemia:

71
# Symbol AA change Variation ID SNP ID
1 ARG1 p.Gly235Arg VAR_000674 rs104893948
2 ARG1 p.Ile11Thr VAR_015594 rs28941474
3 ARG1 p.Gly138Val VAR_015595 rs104893943
4 ARG1 p.Gly27Asp VAR_072164
5 ARG1 p.Gly74Val VAR_072165
6 ARG1 p.Ala125Val VAR_072166
7 ARG1 p.Thr134Ile VAR_072167
8 ARG1 p.Arg180Thr VAR_072168
9 ARG1 p.Arg308Gln VAR_072169 rs377280518

ClinVar genetic disease variations for Argininemia:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 ARG1 ARG1, 4-BP DEL deletion Pathogenic
2 ARG1 ARG1, 1-BP DEL deletion Pathogenic
3 ARG1 NM_000045.3(ARG1): c.871C> T (p.Arg291Ter) single nucleotide variant Pathogenic rs104893940 GRCh37 Chromosome 6, 131904950: 131904950
4 ARG1 NM_000045.3(ARG1): c.869C> G (p.Thr290Ser) single nucleotide variant Pathogenic rs104893942 GRCh37 Chromosome 6, 131904948: 131904948
5 ARG1 NM_000045.3(ARG1): c.365G> A (p.Trp122Ter) single nucleotide variant Pathogenic rs104893947 GRCh37 Chromosome 6, 131902418: 131902418
6 ARG1 NM_000045.3(ARG1): c.703G> C (p.Gly235Arg) single nucleotide variant Pathogenic rs104893948 GRCh37 Chromosome 6, 131904532: 131904532
7 ARG1 ARG1, 1-BP DEL, 842C deletion Pathogenic
8 ARG1 NM_000045.3(ARG1): c.32T> C (p.Ile11Thr) single nucleotide variant Pathogenic rs28941474 GRCh37 Chromosome 6, 131894454: 131894454
9 ARG1 NM_000045.3(ARG1): c.413G> T (p.Gly138Val) single nucleotide variant Pathogenic rs104893943 GRCh37 Chromosome 6, 131902466: 131902466
10 ARG1 NM_000045.3(ARG1): c.57+1G> A single nucleotide variant Pathogenic rs587776539 GRCh37 Chromosome 6, 131894480: 131894480
11 ARG1 ARG1, IVS4AS, A-G, -2 single nucleotide variant Pathogenic
12 ARG1 NM_000045.3(ARG1): c.61C> T (p.Arg21Ter) single nucleotide variant Pathogenic rs104893944 GRCh37 Chromosome 6, 131897806: 131897806
13 ARG1 NM_000045.3(ARG1): c.938delA (p.Lys313Serfs) deletion Pathogenic GRCh38 Chromosome 6, 131583877: 131583877

Expression for Argininemia

Search GEO for disease gene expression data for Argininemia.

Pathways for Argininemia

Pathways related to Argininemia according to KEGG:

36
# Name Kegg Source Accession
1 Arginine biosynthesis hsa00220
2 Arginine and proline metabolism hsa00330

Pathways related to Argininemia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.73 ARG1 ASL ASS1 CPS1 NAGS OTC
2
Show member pathways
13.54 ARG1 ASL ASS1 CPS1 NAGS OTC
3
Show member pathways
13.25 ARG1 ASL ASS1 CPS1 NAGS OTC
4
Show member pathways
11.96 ARG1 ASL ASS1 CPS1 NAGS OTC
5 11.52 ARG1 ASS1 CPS1 OTC
6 11.04 ASL ASS1 CPS1
7
Show member pathways
10.85 ARG1 ASL ASS1 CPS1 NAGS OTC
8
Show member pathways
10.52 ASL ASS1
9
Show member pathways
10.48 ARG1 ASL ASS1 CPS1 NAGS OTC

GO Terms for Argininemia

Cellular components related to Argininemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.26 ASS1 CPS1 NAGS OTC
2 mitochondrial matrix GO:0005759 8.8 CPS1 NAGS OTC

Biological processes related to Argininemia according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.72 ARG1 CPS1 OTC
2 liver development GO:0001889 9.61 ARG1 CPS1 OTC
3 cellular response to glucagon stimulus GO:0071377 9.54 ARG1 CPS1
4 response to steroid hormone GO:0048545 9.52 ARG1 CPS1
5 response to amino acid GO:0043200 9.51 ARG1 CPS1
6 cellular amino acid biosynthetic process GO:0008652 9.5 ASL ASS1 OTC
7 protein homotrimerization GO:0070207 9.49 ARG1 OTC
8 response to amine GO:0014075 9.48 ARG1 CPS1
9 midgut development GO:0007494 9.46 CPS1 OTC
10 urea cycle GO:0000050 9.43 ARG1 ASL ASS1 CPS1 NAGS OTC
11 citrulline biosynthetic process GO:0019240 9.4 CPS1 OTC
12 arginine biosynthetic process via ornithine GO:0042450 9.37 ASL OTC
13 response to zinc ion GO:0010043 9.33 ARG1 CPS1 OTC
14 anion homeostasis GO:0055081 9.26 CPS1 OTC
15 arginine biosynthetic process GO:0006526 9.02 ASL ASS1 CPS1 NAGS OTC

Molecular functions related to Argininemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phospholipid binding GO:0005543 8.96 CPS1 OTC
2 amino acid binding GO:0016597 8.62 ASS1 OTC

Sources for Argininemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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