CSTNU
MCID: CYS019
MIFTS: 45

Cystathioninuria (CSTNU)

Categories: Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Cystathioninuria

MalaCards integrated aliases for Cystathioninuria:

Name: Cystathioninuria 56 12 52 58 73 36 29 13 54 6 15 39 71
Gamma-Cystathionase Deficiency 12 52 58 43 71
Cystathionase Deficiency 56 12 58 73 71
Cystathionine Gamma-Lyase Deficiency Syndrome 58
Cystathione Gamma-Lyase Deficiency Syndrome 12
Cstnu 73

Characteristics:

Orphanet epidemiological data:

58
cystathioninuria
Inheritance: Autosomal recessive; Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
majority of patients are pyridoxine-responsive


HPO:

31
cystathioninuria:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0090142
OMIM 56 219500
KEGG 36 H00182
NCIt 49 C129070
SNOMED-CT 67 13003007 367036006
ICD10 32 E72.19
MESH via Orphanet 44 C535408
ICD10 via Orphanet 33 E72.1
UMLS via Orphanet 72 C0220993 C0268616
Orphanet 58 ORPHA212
UMLS 71 C0220993 C0268616 C3495552

Summaries for Cystathioninuria

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 212 Definition Cystathioninuria is an autosomal recessive disorder caused by cystathionine gamma-lyase deficiency. It is usually pyridoxine-dependent, but in very rare cases it may be non-dependent. It is generally considered to be a benign condition without pathogenic relevance. However, association of cystathioninuria with intellectual impairment has been reported in several cases. Visit the Orphanet disease page for more resources.

MalaCards based summary : Cystathioninuria, also known as gamma-cystathionase deficiency, is related to homocystinuria and neuroblastoma. An important gene associated with Cystathioninuria is CTH (Cystathionine Gamma-Lyase), and among its related pathways/superpathways are Glycine, serine and threonine metabolism and Cysteine and methionine metabolism. Affiliated tissues include neutrophil, liver and testes, and related phenotypes are cystathioninuria and intellectual disability

Disease Ontology : 12 An amino acid metabolic disorder that is characterized by elevated plasma and urinary cystathionine levels that has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the gene encoding cystathionine gamma-lyase (CTH) on chromosome 1p31.

OMIM : 56 Cystathioninuria, an autosomal recessive phenotype with no striking pathologic features, is characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion. Because of the inconsistency and wide variety of disease associations, cystathioninuria is considered to be a benign biochemical anomaly (Mudd et al., 2001). (219500)

KEGG : 36 Hereditary cystathioninuria is caused by deficiency of the activity of cystathionine gamma-lyase, which is normally required for the conversion of methionine into cysteine. Patients with cystathioninuria may have mild to moderate hyperhomocysteinemia.

UniProtKB/Swiss-Prot : 73 Cystathioninuria: Autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.

Wikipedia : 74 Cystathioninuria, also called cystathionase deficiency, is an autosomal recessive metabolic disorder. It... more...

Related Diseases for Cystathioninuria

Graphical network of the top 20 diseases related to Cystathioninuria:



Diseases related to Cystathioninuria

Symptoms & Phenotypes for Cystathioninuria

Human phenotypes related to Cystathioninuria:

58 31 (show all 9)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cystathioninuria 58 31 obligate (100%) Obligate (100%) HP:0003153
2 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
3 cystathioninemia 58 31 frequent (33%) Frequent (79-30%) HP:0003286
4 seizure 31 frequent (33%) HP:0001250
5 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
6 external ear malformation 58 31 occasional (7.5%) Occasional (29-5%) HP:0008572
7 talipes equinovarus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001762
8 nephrolithiasis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000787
9 seizures 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

56
Laboratory Abnormalities:
cystathioninuria
hepatic gamma-cystathionase deficiency

Neurologic:
mental retardation, but majority of patients are normal

Clinical features from OMIM:

219500

Drugs & Therapeutics for Cystathioninuria

Search Clinical Trials , NIH Clinical Center for Cystathioninuria

Cochrane evidence based reviews: gamma-cystathionase deficiency

Genetic Tests for Cystathioninuria

Genetic tests related to Cystathioninuria:

# Genetic test Affiliating Genes
1 Cystathioninuria 29 CTH

Anatomical Context for Cystathioninuria

MalaCards organs/tissues related to Cystathioninuria:

40
Neutrophil, Liver, Testes, Brain, Kidney, Breast

Publications for Cystathioninuria

Articles related to Cystathioninuria:

(show top 50) (show all 121)
# Title Authors PMID Year
1
Genomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH). 56 54 6 61
12574942 2003
2
Ancient origin of the CTH alelle carrying the c.200C>T (p.T67I) variant in patients with cystathioninuria. 61 6 56
20584029 2010
3
Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria. 61 56 54
15887277 2005
4
Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. 56 61
20566639 2010
5
Review of Metabolic Screening Program of Children's Hospital, Vancouver, British Columbia. 1971--1977. 56 61
519848 1979
6
Cystathionase deficiency: evidence for genetic heterogeneity in primary cystathioninuria. 61 56
417288 1978
7
Cystathioninuria in a well baby population. 61 56
5579857 1971
8
Cystathioninuria not associated with vitamin B6 dependency: a probably new type of cystathioninuria. 61 56
5707897 1968
9
Cystathioninuria and renal iminoglycinuria in a pedigree. 61 56
5644557 1968
10
Cystathioninuria in two healty siblings. 56 61
5637757 1968
11
Latent cystathioninuria. 56 61
6082903 1967
12
Cystathioninuria. 56 61
4289134 1967
13
Cystathioninuria: nature of the defect. 56 61
5826521 1965
14
Newborn urine screening experience with over one million infants in the Quebec Network of Genetic Medicine. 56
3128688 1988
15
Urine screening for aminoacidopathies: is it beneficial? Results of a long-term follow-up of cases detected bny screening one millon babies. 56
7411317 1980
16
Cystathioninemia: a benign genetic condition. 56
5420794 1970
17
Cystathioninura. 56
13959884 1963
18
Cystathioniuria. 56
14399948 1959
19
Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration. 61 54
15151507 2004
20
Preeclampsia-Like Features and Partial Lactation Failure in Mice Lacking Cystathionine γ-Lyase-An Animal Model of Cystathioninuria. 61
31319489 2019
21
[Cystathionine γ-lyase]. 61
24491890 2014
22
Methionine excess in diet induces acute lethal hepatitis in mice lacking cystathionine γ-lyase, an animal model of cystathioninuria. 61
22387178 2012
23
Hydrogen sulfide generation in mammals: the molecular biology of cystathionine-β- synthase (CBS) and cystathionine-γ-lyase (CSE). 61
21275900 2011
24
Kinetic properties of polymorphic variants and pathogenic mutants in human cystathionine gamma-lyase. 61
18476726 2008
25
Quebec neonatal mass urinary screening programme: from micromolecules to macromolecules. 61
17570073 2007
26
Hydrogen sulfide as a new endogenous gaseous transmitter in the cardiovascular system. 61
16472173 2006
27
Effect of sulfur amino acids on stimulus-induced superoxide generation and translocation of p47phox and p67phox to cell membrane in human neutrophils and the scavenging of free radical. 61
15698597 2005
28
Age-associated oxidative damage leads to absence of gamma-cystathionase in over 50% of rat lenses: relevance in cataractogenesis. 61
15683713 2005
29
Hepatic gamma-cystathionase deficiency in patients with AIDS. 61
11255419 2001
30
Accumulation of cystathionine, cystathionine ketimine, and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in whole brain and various regions of the brain of D, L-propargylglycine-treated rats. 61
10954021 2000
31
Novel priming compounds of cystathionine metabolites on superoxide generation in human neutrophils. 61
10708546 2000
32
Maternal gamma-cystathionase deficiency: absence of both teratogenic effects and pregnancy complications. 61
10486496 1999
33
Metabolism of cystathionine, N-monoacetylcystathionine, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of D,L-propargylglycine-treated rats. 61
9781627 1998
34
Different effect of diastereoisomers of L-cystathionine sulfoxide on the stimulus coupled responses of human neutrophils. 61
9642137 1998
35
Priming effect of N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine in human neutrophils and tyrosyl phosphorylation of 45 kDa protein. 61
9437538 1997
36
Simultaneous determination of urinary cystathionine, lanthionine, S-(2-aminoethyl)-L-cysteine and their cyclic compounds using liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization. 61
9367221 1997
37
[Cystathioninuria in two families: a clinical and biochemical follow-up]. 61
9082893 1997
38
Identification of cyclic cystathionine sulfoxide and N-acetylcyclic cystathionine in the urine of a patient with cystathioninuria using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system. 61
8843190 1996
39
Effect of cystathionine and cystathionine metabolites on the phosphorylation of tyrosine residues in human neutrophils. 61
8713134 1996
40
Effect of cystathionine ketimine on the stimulus coupled responses of neutrophils and their modulation by various protein kinase inhibitors. 61
8573164 1996
41
Identification of perhydro-1,4-thiazepine-3,5-dicarboxylic acid, cystathionine mono-oxo acids, cystathionine ketimines, cystathionine sulfoxide and N-acetylcystathionine sulfoxide in the urine sample of D,L-propargylglycine treated rats. 61
8868580 1995
42
Simultaneous determination of cystathionine and NAc-cystathionine using liquid chromatography atmospheric pressure chemical ionization mass spectrometry. 61
7710066 1995
43
Identification of N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine in the urine of a patient with cystathioninuria using LC/APCI-MS. 61
8750604 1995
44
Determination of D,L-propargylglycine and N-acetylpropargylglycine in urine and several tissues of D,L-propargylglycine-treated rats using liquid chromatography-mass spectrometry. 61
7866528 1994
45
Identification of new cystathionine mono-oxo acids, S-(3-oxo-3-carboxy-n-propyl) cysteine and S-(2-oxo-2-carboxyethyl) homocysteine, in the urine of a patient with cystathioninuria. 61
8373176 1993
46
[Congenital cystathioninuria. B6-dependent]. 61
8250445 1993
47
Determination of cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in the urine of a patient with cystathioninuria using column liquid chromatography-mass spectrometry. 61
1429979 1992
48
[Inherited metabolic disorders of the transsulfuration pathway]. 61
1404882 1992
49
Homocystinuria, arteriosclerosis, methylmalonic aciduria, and methyltransferase deficiency: a key case revisited. 61
1579271 1992
50
Identification of NAc-HCPC and NAc-beta-CEC, and qualitative analyses of sulphur amino acids in the urine of a patient with cystathioninuria using liquid chromatography/atmospheric pressure ionization mass spectrometry. 61
1793738 1991

Variations for Cystathioninuria

ClinVar genetic disease variations for Cystathioninuria:

6 (show top 50) (show all 58) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CTH CTH, 2-BP DEL, 940CTdeletion Pathogenic 2937
2 CTH CTH, 1-BP DEL, 1220Cdeletion Pathogenic 2938
3 CTH NM_001902.6(CTH):c.718C>G (p.Gln240Glu)SNV Pathogenic 2940 rs28941786 1:70896071-70896071 1:70430388-70430388
4 CTH NM_001902.6(CTH):c.793C>T (p.Arg265Ter)SNV Likely pathogenic 225330 rs773107808 1:70897834-70897834 1:70432151-70432151
5 CTH NM_001902.6(CTH):c.346+7G>ASNV Conflicting interpretations of pathogenicity 298029 rs186217898 1:70883722-70883722 1:70418039-70418039
6 CTH NM_001902.6(CTH):c.200C>T (p.Thr67Ile)SNV Conflicting interpretations of pathogenicity 2939 rs28941785 1:70881670-70881670 1:70415987-70415987
7 CTH NM_001902.6(CTH):c.864G>A (p.Lys288=)SNV Conflicting interpretations of pathogenicity 298035 rs368097625 1:70897905-70897905 1:70432222-70432222
8 CTH NM_001902.6(CTH):c.995T>C (p.Leu332Pro)SNV Uncertain significance 298036 rs767542599 1:70899628-70899628 1:70433945-70433945
9 CTH NM_001902.6(CTH):c.1033G>A (p.Glu345Lys)SNV Uncertain significance 298037 rs771762248 1:70900841-70900841 1:70435158-70435158
10 CTH NM_001902.6(CTH):c.*630G>ASNV Uncertain significance 298054 rs543839341 1:70905440-70905440 1:70439757-70439757
11 CTH NM_001902.6(CTH):c.*631C>TSNV Uncertain significance 298055 rs559469669 1:70905441-70905441 1:70439758-70439758
12 CTH NM_001902.6(CTH):c.381A>G (p.Glu127=)SNV Uncertain significance 298030 rs886046511 1:70887283-70887283 1:70421600-70421600
13 CTH NM_001902.6(CTH):c.*545C>TSNV Uncertain significance 298051 rs886046516 1:70905355-70905355 1:70439672-70439672
14 CTH NM_001902.6(CTH):c.-3A>GSNV Uncertain significance 298028 rs757363405 1:70877096-70877096 1:70411413-70411413
15 CTH NM_001902.6(CTH):c.*522_*523insTAAinsertion Uncertain significance 298047 rs886046514 1:70905332-70905333 1:70439649-70439650
16 CTH NM_001902.6(CTH):c.465G>A (p.Trp155Ter)SNV Uncertain significance 631615 rs1032541755 1:70889976-70889976 1:70424293-70424293
17 CTH NM_001902.6(CTH):c.1052+1G>ASNV Uncertain significance 631616 rs570239863 1:70900861-70900861 1:70435178-70435178
18 CTH NM_001902.6(CTH):c.1052+1G>CSNV Uncertain significance 631617 rs570239863 1:70900861-70900861 1:70435178-70435178
19 CTH NM_001902.6(CTH):c.15C>A (p.Asp5Glu)SNV Uncertain significance 876319 1:70877113-70877113 1:70411430-70411430
20 CTH NM_001902.6(CTH):c.685T>C (p.Cys229Arg)SNV Uncertain significance 874346 1:70896038-70896038 1:70430355-70430355
21 CTH NM_001902.6(CTH):c.710G>T (p.Arg237Leu)SNV Uncertain significance 874347 1:70896063-70896063 1:70430380-70430380
22 CTH NM_001902.6(CTH):c.794G>T (p.Arg265Leu)SNV Uncertain significance 874349 1:70897835-70897835 1:70432152-70432152
23 CTH NM_001902.6(CTH):c.816C>T (p.Asn272=)SNV Uncertain significance 874350 1:70897857-70897857 1:70432174-70432174
24 CTH NM_001902.6(CTH):c.*217G>TSNV Uncertain significance 875273 1:70905027-70905027 1:70439344-70439344
25 CTH NM_001902.6(CTH):c.*336A>GSNV Uncertain significance 875274 1:70905146-70905146 1:70439463-70439463
26 CTH NM_001902.6(CTH):c.*411G>CSNV Uncertain significance 876228 1:70905221-70905221 1:70439538-70439538
27 CTH NM_001902.6(CTH):c.*513T>ASNV Uncertain significance 876229 1:70905323-70905323 1:70439640-70439640
28 CTH NM_001902.6(CTH):c.*522T>ASNV Uncertain significance 876230 1:70905332-70905332 1:70439649-70439649
29 CTH NM_001902.6(CTH):c.*546G>ASNV Uncertain significance 876361 1:70905356-70905356 1:70439673-70439673
30 CTH NM_001902.6(CTH):c.*588C>TSNV Uncertain significance 876362 1:70905398-70905398 1:70439715-70439715
31 CTH NM_001902.6(CTH):c.*681G>ASNV Uncertain significance 874404 1:70905491-70905491 1:70439808-70439808
32 CTH NM_001902.6(CTH):c.*693G>TSNV Uncertain significance 874405 1:70905503-70905503 1:70439820-70439820
33 CTH NM_001902.6(CTH):c.647-15G>CSNV Uncertain significance 874345 1:70895985-70895985 1:70430302-70430302
34 CTH NM_001902.6(CTH):c.724+10A>GSNV Uncertain significance 874348 1:70896087-70896087 1:70430404-70430404
35 CTH NM_001902.6(CTH):c.495G>T (p.Lys165Asn)SNV Uncertain significance 298032 rs375562313 1:70890006-70890006 1:70424323-70424323
36 CTH NM_001902.6(CTH):c.541G>A (p.Asp181Asn)SNV Uncertain significance 298033 rs748301555 1:70890052-70890052 1:70424369-70424369
37 CTH NM_001902.6(CTH):c.*98G>ASNV Uncertain significance 298041 rs886046512 1:70904908-70904908 1:70439225-70439225
38 CTH NM_001902.6(CTH):c.*334T>ASNV Uncertain significance 298043 rs886046513 1:70905144-70905144 1:70439461-70439461
39 CTH NM_001902.6(CTH):c.*371G>ASNV Uncertain significance 298045 rs183166406 1:70905181-70905181 1:70439498-70439498
40 CTH NM_001902.6(CTH):c.*587G>ASNV Uncertain significance 298052 rs886046517 1:70905397-70905397 1:70439714-70439714
41 CTH NM_001902.6(CTH):c.430G>C (p.Glu144Gln)SNV Uncertain significance 298031 rs773089704 1:70887332-70887332 1:70421649-70421649
42 CTH NM_001902.6(CTH):c.589-3C>TSNV Uncertain significance 298034 rs201568449 1:70895474-70895474 1:70429791-70429791
43 CTH NM_001902.6(CTH):c.*260T>CSNV Uncertain significance 298042 rs768499542 1:70905070-70905070 1:70439387-70439387
44 CTH NM_001902.6(CTH):c.*370C>TSNV Uncertain significance 298044 rs868533214 1:70905180-70905180 1:70439497-70439497
45 CTH NM_001902.6(CTH):c.*527A>TSNV Uncertain significance 298049 rs886046515 1:70905337-70905337 1:70439654-70439654
46 CTH NM_001902.6(CTH):c.*632G>ASNV Uncertain significance 298056 rs565236096 1:70905442-70905442 1:70439759-70439759
47 CTH NM_153742.4(CTH):c.-151T>CSNV Uncertain significance 298026 rs767468686 1:70876948-70876948 1:70411265-70411265
48 CTH NM_001902.6(CTH):c.-140A>TSNV Likely benign 298027 rs17131292 1:70876959-70876959 1:70411276-70411276
49 CTH NM_001902.6(CTH):c.129G>A (p.Leu43=)SNV Likely benign 876320 1:70877227-70877227 1:70411544-70411544
50 CTH NM_001902.5(CTH):c.*735G>ASNV Likely benign 368879 rs584229 1:70905545-70905545 1:70439862-70439862

UniProtKB/Swiss-Prot genetic disease variations for Cystathioninuria:

73
# Symbol AA change Variation ID SNP ID
1 CTH p.Thr67Ile VAR_015450 rs28941785
2 CTH p.Gln240Glu VAR_015451 rs28941786

Expression for Cystathioninuria

Search GEO for disease gene expression data for Cystathioninuria.

Pathways for Cystathioninuria

Pathways related to Cystathioninuria according to KEGG:

36
# Name Kegg Source Accession
1 Glycine, serine and threonine metabolism hsa00260
2 Cysteine and methionine metabolism hsa00270

GO Terms for Cystathioninuria

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

# Name GO ID Score Top Affiliating Genes
1 cellular amino acid biosynthetic process GO:0008652 9.4 CTH CBSL
2 purine-containing compound salvage GO:0043101 9.37 GMPR DGUOK
3 sulfur amino acid catabolic process GO:0000098 9.32 MPST CTH
4 cysteine biosynthetic process GO:0019344 9.26 CTH CBSL
5 cysteine biosynthetic process via cystathionine GO:0019343 9.16 CTH CBSL
6 transsulfuration GO:0019346 9.13 MPST CTH CBSL
7 hydrogen sulfide biosynthetic process GO:0070814 8.8 MPST CTH CBSL

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

# Name GO ID Score Top Affiliating Genes
1 pyridoxal phosphate binding GO:0030170 8.96 CTH CBSL
2 lyase activity GO:0016829 8.8 PCBD1 CTH CBSL

Sources for Cystathioninuria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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