MCID: XNT011
MIFTS: 34

Xanthinuria, Type Ii

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

Aliases & Classifications for Xanthinuria, Type Ii

MalaCards integrated aliases for Xanthinuria, Type Ii:

Name: Xanthinuria, Type Ii 57 55 73
Xanthinuria Type 2 53 29 6
Xdh and Aox Dual Deficiency 53 59
Xan2 57 75
Xanthine Dehydrogenase and Xanthine Aldehyde Oxidase Dual Deficiency 59
Xanthine Dehydrogenase and Aldehyde Oxidase, Combined Deficiency of 57
Xanthine Dehydrogenase and Aldehyde Oxidase Combined Deficiency of 53
Combined Deficiency of Xanthine Dehydrogenase and Aldehyde Oxidase 75
Xanthic Urolithiasis 75
Type Ii Xanthinuria 53
Xanthinuria Type Ii 59
Type 2 Xanthinuria 53
Xanthinuria 2 75

Characteristics:

Orphanet epidemiological data:

59
xanthinuria type ii
Inheritance: Autosomal recessive;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable age at onset
some patients may be asymptomatic
cannot metabolize allopurinol
one patient with a heterozygous mutation has been reported (last curated july 2016)


HPO:

32
xanthinuria, type ii:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 603592
Orphanet 59 ORPHA93602
UMLS via Orphanet 74 C1863688
ICD10 via Orphanet 34 E79.8
MedGen 42 C1863688

Summaries for Xanthinuria, Type Ii

OMIM : 57 Xanthinuria type II is an autosomal recessive inborn error of metabolism resulting from a defect in the synthesis of the molybdenum cofactor, which is necessary for the 2 enzymes that degrade xanthine: XDH (607633) and AOX1 (602841). Most individuals with type II xanthinuria are asymptomatic, but some develop urinary tract calculi, acute renal failure, or myositis due to tissue deposition of xanthine. Laboratory studies show increased serum and urinary hypoxanthine and xanthine and decreased serum and urinary uric acid (summary by Ichida et al., 2001). Two clinically similar but distinct forms of xanthinuria are recognized. In type I xanthinuria (XAN1; 278300), there is an isolated deficiency of xanthine dehydrogenase resulting from mutation in the XDH gene; in type II, there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase. Type I patients can metabolize allopurinol, whereas type II patients cannot (Simmonds et al., 1995). (603592)

MalaCards based summary : Xanthinuria, Type Ii, also known as xanthinuria type 2, is related to molybdenum cofactor deficiency and xanthinuria, type i. An important gene associated with Xanthinuria, Type Ii is MOCOS (Molybdenum Cofactor Sulfurase), and among its related pathways/superpathways are Drug metabolism - cytochrome P450 and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include kidney, and related phenotypes are renal insufficiency and nephrolithiasis

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 93602Disease definitionType II xanthinuria, a type of classical xanthinuria (see this term), is a rare autosomal recessive disorder of purine metabolism (see this term) characterized by the deficiency of both xanthine dehydrogenase and aldehyde oxidase, leading to the formation of urinary xanthine urolithiasis and leading, in some patients, to kidney failure. Other less common manifestations include arthropathy, myopathy and duodenal ulcer, while some patients remain asymptomatic.Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 75 Xanthinuria 2: A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. In addition, XAN2 patients cannot metabolize allopurinol into oxypurinol due to dual deficiency of xanthine dehydrogenase and aldehyde oxidase.

Related Diseases for Xanthinuria, Type Ii

Diseases in the Xanthinuria family:

Xanthinuria, Type I Xanthinuria, Type Ii
Hereditary Xanthinuria

Diseases related to Xanthinuria, Type Ii via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 molybdenum cofactor deficiency 30.7 AOX1 XDH
2 xanthinuria, type i 30.2 AOX1 XDH
3 xanthinuria 30.2 AOX1 MOCOS XDH
4 hereditary xanthinuria 28.8 AOX1 XDH
5 molybdenum cofactor deficiency, complementation group a 11.5
6 autism 9.9
7 nephrocalcinosis 9.9
8 cystic kidney disease 9.9
9 purine-pyrimidine metabolic disorder 8.7 AOX1 MOCOS XDH

Graphical network of the top 20 diseases related to Xanthinuria, Type Ii:



Diseases related to Xanthinuria, Type Ii

Symptoms & Phenotypes for Xanthinuria, Type Ii

Symptoms via clinical synopsis from OMIM:

57
Genitourinary Kidneys:
renal stones (in some patients)
renal failure (in some patients)

Laboratory Abnormalities:
increased serum and urinary hypoxanthine
increased serum and urinary xanthine
hypouricemia
decreased or absent urinary uric acid
decreased activities of xanthine dehydrogenase and xanthine oxidase

Muscle Soft Tissue:
myopathy due to xanthine accumulation (in some patients)


Clinical features from OMIM:

603592

Human phenotypes related to Xanthinuria, Type Ii:

32
# Description HPO Frequency HPO Source Accession
1 renal insufficiency 32 occasional (7.5%) HP:0000083
2 nephrolithiasis 32 occasional (7.5%) HP:0000787
3 hypouricemia 32 HP:0003537

Drugs & Therapeutics for Xanthinuria, Type Ii

Search Clinical Trials , NIH Clinical Center for Xanthinuria, Type Ii

Genetic Tests for Xanthinuria, Type Ii

Genetic tests related to Xanthinuria, Type Ii:

# Genetic test Affiliating Genes
1 Xanthinuria Type 2 29 MOCOS

Anatomical Context for Xanthinuria, Type Ii

MalaCards organs/tissues related to Xanthinuria, Type Ii:

41
Kidney

Publications for Xanthinuria, Type Ii

Articles related to Xanthinuria, Type Ii:

# Title Authors Year
1
Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type II). ( 29935280 )
2018
2
Hereditary xanthinuria type II associated with mental delay, autism, cortical renal cysts, nephrocalcinosis, osteopenia, and hair and teeth defects. ( 14627688 )
2003
3
Identification of a new point mutation in the human molybdenum cofactor sulferase gene that is responsible for xanthinuria type II. ( 14624414 )
2003
4
Mutation of human molybdenum cofactor sulfurase gene is responsible to classical xanthinuria type II. ( 11302742 )
2001

Variations for Xanthinuria, Type Ii

UniProtKB/Swiss-Prot genetic disease variations for Xanthinuria, Type Ii:

75
# Symbol AA change Variation ID SNP ID
1 MOCOS p.Ala57Pro VAR_027528 rs886037854
2 MOCOS p.Thr294Ile VAR_027533 rs577279030
3 MOCOS p.Arg776Cys VAR_045899 rs750896617

ClinVar genetic disease variations for Xanthinuria, Type Ii:

6
(show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 MOCOS NM_017947.3(MOCOS): c.1255C> T (p.Arg419Ter) single nucleotide variant Pathogenic rs142150953 GRCh38 Chromosome 18, 36213402: 36213402
2 MOCOS NM_017947.3(MOCOS): c.1255C> T (p.Arg419Ter) single nucleotide variant Pathogenic rs142150953 GRCh37 Chromosome 18, 33793365: 33793365
3 MOCOS NM_017947.3(MOCOS): c.169G> C (p.Ala57Pro) single nucleotide variant Pathogenic rs886037854 GRCh38 Chromosome 18, 36195283: 36195283
4 MOCOS NM_017947.3(MOCOS): c.169G> C (p.Ala57Pro) single nucleotide variant Pathogenic rs886037854 GRCh37 Chromosome 18, 33775246: 33775246
5 MOCOS NM_017947.3(MOCOS): c.2326C> T (p.Arg776Cys) single nucleotide variant Pathogenic rs750896617 GRCh37 Chromosome 18, 33840055: 33840055
6 MOCOS NM_017947.3(MOCOS): c.2326C> T (p.Arg776Cys) single nucleotide variant Pathogenic rs750896617 GRCh38 Chromosome 18, 36260092: 36260092
7 MOCOS NM_017947.3(MOCOS): c.1037dupA (p.Gln347Alafs) duplication Pathogenic rs886037855 GRCh38 Chromosome 18, 36205095: 36205095
8 MOCOS NM_017947.3(MOCOS): c.1037dupA (p.Gln347Alafs) duplication Pathogenic rs886037855 GRCh37 Chromosome 18, 33785058: 33785058
9 XDH NM_000379.3(XDH): c.1134C> T (p.Gly378=) single nucleotide variant Benign/Likely benign rs45612738 GRCh37 Chromosome 2, 31602841: 31602841
10 XDH NM_000379.3(XDH): c.1134C> T (p.Gly378=) single nucleotide variant Benign/Likely benign rs45612738 GRCh38 Chromosome 2, 31379975: 31379975
11 XDH NM_000379.3(XDH): c.1184A> T (p.Lys395Met) single nucleotide variant Benign/Likely benign rs34929837 GRCh37 Chromosome 2, 31602791: 31602791
12 XDH NM_000379.3(XDH): c.1184A> T (p.Lys395Met) single nucleotide variant Benign/Likely benign rs34929837 GRCh38 Chromosome 2, 31379925: 31379925
13 XDH NM_000379.3(XDH): c.1820G> A (p.Arg607Gln) single nucleotide variant Uncertain significance rs45442092 GRCh37 Chromosome 2, 31595130: 31595130
14 XDH NM_000379.3(XDH): c.1820G> A (p.Arg607Gln) single nucleotide variant Uncertain significance rs45442092 GRCh38 Chromosome 2, 31372264: 31372264
15 MOCOS NM_017947.3(MOCOS): c.309G> A (p.Ala103=) single nucleotide variant Benign rs149639104 GRCh37 Chromosome 18, 33779655: 33779655
16 MOCOS NM_017947.3(MOCOS): c.309G> A (p.Ala103=) single nucleotide variant Benign rs149639104 GRCh38 Chromosome 18, 36199692: 36199692

Expression for Xanthinuria, Type Ii

Search GEO for disease gene expression data for Xanthinuria, Type Ii.

Pathways for Xanthinuria, Type Ii

Pathways related to Xanthinuria, Type Ii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.95 AOX1 XDH
2
Show member pathways
11.76 AOX1 MOCOS
3 10.39 AOX1 XDH
4 9.53 AOX1 XDH

GO Terms for Xanthinuria, Type Ii

Biological processes related to Xanthinuria, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 electron transport chain GO:0022900 8.96 AOX1 XDH
2 xanthine catabolic process GO:0009115 8.62 AOX1 XDH

Molecular functions related to Xanthinuria, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 iron ion binding GO:0005506 9.46 AOX1 XDH
2 electron transfer activity GO:0009055 9.43 AOX1 XDH
3 flavin adenine dinucleotide binding GO:0050660 9.4 AOX1 XDH
4 iron-sulfur cluster binding GO:0051536 9.37 AOX1 XDH
5 2 iron, 2 sulfur cluster binding GO:0051537 9.32 AOX1 XDH
6 oxidoreductase activity, acting on CH-OH group of donors GO:0016614 9.26 AOX1 XDH
7 molybdopterin cofactor binding GO:0043546 9.16 AOX1 XDH
8 xanthine dehydrogenase activity GO:0004854 8.96 AOX1 XDH
9 oxidoreductase activity, acting on the aldehyde or oxo group of donors GO:0016903 8.62 AOX1 XDH

Sources for Xanthinuria, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....