TYRSN3
MCID: TYR011
MIFTS: 42

Tyrosinemia, Type Iii (TYRSN3)

Categories: Blood diseases, Cancer diseases, Endocrine diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Tyrosinemia, Type Iii

MalaCards integrated aliases for Tyrosinemia, Type Iii:

Name: Tyrosinemia, Type Iii 56 13 39 71
Tyrosinemia Type Iii 12 52 58 73 15
4-Hydroxyphenylpyruvate Dioxygenase Deficiency 56 52 73 29
Tyrosinemia Type 3 52 58 6
4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 56 73
Tyrsn3 56 73
Tyrosinemia Due to 4-Hydroxyphenylpyruvate Dioxygenase Deficiency 58
Tyrosinemia Due to 4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 58
4-Alpha Hydroxyphenylpyruvate Dioxygenase Deficiency 52
4-Alpha Hydroxyphenylpyruvic Acid Oxidase Deficiency 52
Tyrosinemia Due to Hpd Deficiency 58
Tyrosinemia 3 73

Characteristics:

Orphanet epidemiological data:

58
tyrosinemia type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
allelic to hawkinsinuria


HPO:

31
tyrosinemia, type iii:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0050727
OMIM 56 276710
OMIM Phenotypic Series 56 PS276700
MeSH 43 D020176
ICD10 via Orphanet 33 E70.2
UMLS via Orphanet 72 C0268623
Orphanet 58 ORPHA69723
MedGen 41 C0268623
UMLS 71 C0268623

Summaries for Tyrosinemia, Type Iii

NIH Rare Diseases : 52 Tyrosinemia type 3 is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine, a building block of most proteins . This condition is caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase, one of the enzymes required for the multi-step process that breaks down tyrosine. This enzyme shortage is caused by mutations in the HPD gene . Characteristic features include intellectual disability , seizures , and periodic loss of balance and coordination (intermittent ataxia ). Tyrosinemia type 3 is inherited in an autosomal recessive manner.

MalaCards based summary : Tyrosinemia, Type Iii, also known as tyrosinemia type iii, is related to tyrosinemia and abdominal obesity-metabolic syndrome 1, and has symptoms including seizures An important gene associated with Tyrosinemia, Type Iii is HPD (4-Hydroxyphenylpyruvate Dioxygenase), and among its related pathways/superpathways are Metabolism and Viral mRNA Translation. Affiliated tissues include liver, kidney and neutrophil, and related phenotypes are seizures and intellectual disability, mild

Disease Ontology : 12 A tyrosinemia that has material basis in deficiency of 4-hydroxyphenylpyruvate dioxygenase disrupting the break down of tyrosine.

OMIM : 56 Tyrosinemia type III is an autosomal recessive disorder caused by a deficiency in the activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) and is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into urine. Patients with this disorder have mild mental retardation and/or convulsions, with the absence of liver damage (summary by Tomoeda et al., 2000). (276710)

UniProtKB/Swiss-Prot : 73 Tyrosinemia 3: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild mental retardation.

Wikipedia : 74 Tyrosinemia type III is a rare disorder caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate... more...

Related Diseases for Tyrosinemia, Type Iii

Graphical network of the top 20 diseases related to Tyrosinemia, Type Iii:



Diseases related to Tyrosinemia, Type Iii

Symptoms & Phenotypes for Tyrosinemia, Type Iii

Human phenotypes related to Tyrosinemia, Type Iii:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 seizures 31 HP:0001250
2 intellectual disability, mild 31 HP:0001256
3 abnormality of the liver 31 HP:0001392
4 4-hydroxyphenylpyruvic aciduria 31 HP:0003161
5 4-hydroxyphenylacetic aciduria 31 HP:0003607
6 hypertyrosinemia 31 HP:0003231

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
mental retardation, mild

Abdomen Liver:
normal liver function

Laboratory Abnormalities:
4-hydroxyphenylpyruvic aciduria
4-hydroxyphenylacetic aciduria
4-hydroxyphenylpyruvic acid dioxygenase deficiency (hpd)
tyrosinemia
4-hydroxyphenyllactic aciduria

Clinical features from OMIM:

276710

UMLS symptoms related to Tyrosinemia, Type Iii:


seizures

MGI Mouse Phenotypes related to Tyrosinemia, Type Iii:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 9.02 FAH GALNS GSTZ1 HGD HPD

Drugs & Therapeutics for Tyrosinemia, Type Iii

Search Clinical Trials , NIH Clinical Center for Tyrosinemia, Type Iii

Genetic Tests for Tyrosinemia, Type Iii

Genetic tests related to Tyrosinemia, Type Iii:

# Genetic test Affiliating Genes
1 4-Hydroxyphenylpyruvate Dioxygenase Deficiency 29 HPD

Anatomical Context for Tyrosinemia, Type Iii

MalaCards organs/tissues related to Tyrosinemia, Type Iii:

40
Liver, Kidney, Neutrophil, Bone, Eye, Skin, Prostate

Publications for Tyrosinemia, Type Iii

Articles related to Tyrosinemia, Type Iii:

(show all 21)
# Title Authors PMID Year
1
Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. 61 56 6
10942115 2000
2
Tyrosinemia type III: diagnosis and ten-year follow-up. 61 56 6
9343288 1997
3
Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. 61 56
11073718 2000
4
Outcome of tyrosinaemia type III. 56
11916315 2001
5
A nonsense mutation in the 4-hydroxyphenylpyruvic acid dioxygenase gene (Hpd) causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III. 56
7774914 1995
6
A murine model for type III tyrosinemia: lack of immunologically detectable 4-hydroxyphenylpyruvic acid dioxygenase enzyme protein in a novel mouse strain with hypertyrosinemia. 56
2014797 1991
7
Putative genetic deficiency of 4-hydroxyphenylpyruvic acid dioxygenase in mice: a murine model for hereditary tyrosinaemia type III. 56
2246865 1990
8
Four-hydroxyphenylpyruvic acid oxidase deficiency with normal fumarylacetoacetase: a new variant form of hereditary hypertyrosinemia. 56
6828337 1983
9
Chronic tyrosinemia associated with 4-hydroxyphenylpyruvate dioxygenase deficiency with acute intermittent ataxia and without visceral and bone involvement. 56
6132360 1983
10
An inborn defect in the metabolism of tyrosine in infants on a normal diet. 56
16748849 1960
11
In-Silico analysis of missense SNPs in Human HPPD gene associated with Tyrosinemia type III and Hawkinsinuria. 61
31054541 2019
12
Hawkinsinuria With Direct Hyperbilirubinemia in Egyptian-Lebanese Boy. 61
30984715 2019
13
Markers of cognitive function in individuals with metabolic disease: Morquio syndrome and tyrosinemia type III. 61
29741470 2018
14
A Case of Tyrosinemia Type III with Status Epilepticus and Mental Retardation. 61
29456978 2018
15
Tyrosinemia type III in an asymptomatic girl. 61
28649543 2015
16
Scavenging properties of neutrophil 4-hydroxyphenylpyruvate dioxygenase are based on a hypothesis that does not stand up to scrutiny. 61
25443415 2014
17
Tyrosinemia Type III detected via neonatal screening: management and outcome. 61
23036342 2012
18
Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III. 61
18657947 2009
19
Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III. 61
17560158 2007
20
The genetic tyrosinemias. 61
16602095 2006
21
[Hereditary tyrosinemia type III]. 61
9590008 1998

Variations for Tyrosinemia, Type Iii

ClinVar genetic disease variations for Tyrosinemia, Type Iii:

6 (show all 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HPD NM_002150.3(HPD):c.479A>G (p.Tyr160Cys)SNV Pathogenic 1573 rs137852865 12:122287632-122287632 12:121849726-121849726
2 HPD NM_002150.3(HPD):c.774T>G (p.Tyr258Ter)SNV Pathogenic 1574 rs137852866 12:122284825-122284825 12:121846919-121846919
3 HPD NM_002150.3(HPD):c.600C>G (p.Tyr200Ter)SNV Pathogenic 1575 rs137852867 12:122285117-122285117 12:121847211-121847211
4 HPD NC_000012.11:g.(?_122281596)_(122285140_?)deldeletion Pathogenic 529472 12:122281596-122285140 12:121843690-121847234
5 HPD NM_002150.3(HPD):c.75G>A (p.Trp25Ter)SNV Pathogenic 529468 rs367674632 12:122295681-122295681 12:121857775-121857775
6 HPD NM_002150.3(HPD):c.43C>T (p.Arg15Ter)SNV Pathogenic 570062 rs775747384 12:122295713-122295713 12:121857807-121857807
7 HPD NM_002150.3(HPD):c.158dup (p.Ser54fs)duplication Pathogenic 642856 12:122295273-122295274 12:121857367-121857368
8 HPD NM_002150.3(HPD):c.1005C>G (p.Ile335Met)SNV Conflicting interpretations of pathogenicity 1576 rs137852868 12:122277904-122277904 12:121839998-121839998
9 HPD NM_002150.3(HPD):c.109T>C (p.Cys37Arg)SNV Uncertain significance 529467 rs1246785384 12:122295323-122295323 12:121857417-121857417
10 HPD NC_000012.11:g.(?_122277614)_(122277974_?)deldeletion Uncertain significance 529471 12:122277614-122277974 12:121839708-121840068
11 HPD NM_002150.3(HPD):c.1151del (p.Met384fs)deletion Uncertain significance 529466 rs1555339247 12:122277665-122277665 12:121839759-121839759
12 HPD NM_002150.3(HPD):c.104T>C (p.Phe35Ser)SNV Uncertain significance 638896 12:122295328-122295328 12:121857422-121857422
13 HPD NM_002150.3(HPD):c.485C>T (p.Ala162Val)SNV Uncertain significance 566973 rs1566570874 12:122287626-122287626 12:121849720-121849720
14 HPD NM_002150.3(HPD):c.1120G>A (p.Glu374Lys)SNV Uncertain significance 638895 12:122277696-122277696 12:121839790-121839790
15 HPD NM_002150.3(HPD):c.544G>A (p.Asp182Asn)SNV Uncertain significance 573513 rs750446552 12:122286957-122286957 12:121849051-121849051
16 HPD NM_002150.3(HPD):c.760-7C>TSNV Likely benign 529469 rs748133768 12:122284846-122284846 12:121846940-121846940
17 HPD NM_002150.3(HPD):c.1018G>T (p.Val340Leu)SNV Benign/Likely benign 307478 rs36023382 12:122277891-122277891 12:121839985-121839985

UniProtKB/Swiss-Prot genetic disease variations for Tyrosinemia, Type Iii:

73
# Symbol AA change Variation ID SNP ID
1 HPD p.Tyr160Cys VAR_015445 rs137852865
2 HPD p.Ala268Val VAR_015447
3 HPD p.Ile335Met VAR_015448

Expression for Tyrosinemia, Type Iii

Search GEO for disease gene expression data for Tyrosinemia, Type Iii.

Pathways for Tyrosinemia, Type Iii

Pathways related to Tyrosinemia, Type Iii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.39 TAT HPD HGD GSTZ1 GALNS FAH
2
Show member pathways
13.12 TAT HPD HGD GSTZ1 FAH
3
Show member pathways
11.44 TAT HPD HGD GSTZ1 FAH
4 11.33 TAT FAH
5
Show member pathways
10.9 TAT HPD HGD GSTZ1 FAH
6
Show member pathways
10.52 TAT HPD

GO Terms for Tyrosinemia, Type Iii

Cellular components related to Tyrosinemia, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 8.92 HPD HGD GALNS FAH

Biological processes related to Tyrosinemia, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 aromatic amino acid family metabolic process GO:0009072 9.46 TAT HPD GSTZ1 FAH
2 L-phenylalanine catabolic process GO:0006559 9.35 TAT HPD HGD GSTZ1 FAH
3 cellular amino acid metabolic process GO:0006520 9.26 TAT HGD
4 tyrosine catabolic process GO:0006572 9.02 TAT HPD HGD GSTZ1 FAH

Molecular functions related to Tyrosinemia, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 dioxygenase activity GO:0051213 8.62 HPD HGD

Sources for Tyrosinemia, Type Iii

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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