TYRSN3
MCID: TYR011
MIFTS: 44

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 58 13 41 74
4-Hydroxyphenylpyruvate Dioxygenase Deficiency 58 54 76 30 6
Tyrosinemia Type Iii 12 54 60 76 15
4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 58 76
Tyrosinemia Type 3 54 60
Tyrsn3 58 76
Tyrosinemia Due to 4-Hydroxyphenylpyruvate Dioxygenase Deficiency 60
Tyrosinemia Due to 4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 60
4-Alpha Hydroxyphenylpyruvate Dioxygenase Deficiency 54
4-Alpha Hydroxyphenylpyruvic Acid Oxidase Deficiency 54
4-Hydroxyphenylpyruvate Dioxygenase 13
Tyrosinemia Due to Hpd Deficiency 60
Tyrosinemia 3 76

Characteristics:

Orphanet epidemiological data:

60
tyrosinemia type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
allelic to hawkinsinuria


HPO:

33
tyrosinemia, type iii:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0050727
OMIM 58 276710
MeSH 45 D020176
ICD10 via Orphanet 35 E70.2
UMLS via Orphanet 75 C0268623
Orphanet 60 ORPHA69723
MedGen 43 C0268623
UMLS 74 C0268623

Summaries for Tyrosinemia, Type Iii

NIH Rare Diseases : 54 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 4-hydroxyphenylpyruvate dioxygenase deficiency, is related to tyrosinemia and hypertelorism, preauricular sinus, punctal pits, and deafness, 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 Amino Acid metabolism and Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism. The drug Nitisinone has been mentioned in the context of this disorder. Affiliated tissues include kidney, bone 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 : 58 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 : 76 Tyrosinemia 3: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild mental retardation.

Wikipedia : 77 Tyrosinemia type III is a rare disorder caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate... more...

Related Diseases for Tyrosinemia, Type Iii

Diseases in the Tyrosinemia family:

Tyrosinemia, Type Ii Tyrosinemia, Type I
Tyrosinemia, Type Iii

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

(show all 14)
# Related Disease Score Top Affiliating Genes
1 tyrosinemia 29.9 FAH HPD TAT
2 hypertelorism, preauricular sinus, punctal pits, and deafness 10.6
3 chromophobe renal cell carcinoma 10.4
4 renal oncocytoma 10.4
5 polycystic kidney disease 10.4
6 peripheral nervous system disease 10.2
7 neuropathy 10.2
8 primary orthostatic tremor 10.2
9 hawkinsinuria 10.0
10 status epilepticus 10.0
11 morquio syndrome 10.0
12 tyrosinemia, type i 9.8 FAH HPD
13 tyrosinemia, type ii 9.8 FAH TAT
14 alkaptonuria 9.7 FAH HPD

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:

33 (show all 6)
# Description HPO Frequency HPO Source Accession
1 seizures 33 HP:0001250
2 intellectual disability, mild 33 HP:0001256
3 abnormality of the liver 33 HP:0001392
4 4-hydroxyphenylpyruvic aciduria 33 HP:0003161
5 4-hydroxyphenylacetic aciduria 33 HP:0003607
6 hypertyrosinemia 33 HP:0003231

Symptoms via clinical synopsis from OMIM:

58
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:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 8.8 FAH GALNS HPD

Drugs & Therapeutics for Tyrosinemia, Type Iii

Drugs for Tyrosinemia, Type Iii (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nitisinone Approved, Investigational Phase 2, Phase 3,Phase 3,Phase 1 104206-65-7 115355

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria Unknown status NCT01390077 Phase 2, Phase 3 Nitisinone
2 Efficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Nitisinone in HT-1 Completed NCT02323529 Phase 3 Nitisinone
3 Phase II Study of the Enzyme Inhibitor NTBC for Tyrosinemia Type I Completed NCT00004333 Phase 2 NTBC
4 Bioequivalence Study of Two Oral Nitisinone Formulations to Treat Hereditary Tyrosinemia (HT-1) Completed NCT02750345 Phase 1 Nitisinone;Nitisinone Baked Tablet;Orfadin
5 Bioavailability Food-Effect Study of an Oral Nitisinone Formulation to Treat Hereditary Tyrosinemia (HT-1) Completed NCT02750332 Phase 1 Nitisinone
6 Taste and Palatability of Orfadin Suspension Completed NCT01734889 Phase 1 Nitisinone
7 Bioequivalence Study of Two Nitisinone Formulations Compared to Orfadin Completed NCT02750709 Phase 1 Nitisinone;Nitisinone 10 mg Tablet High Compritol;Orfadin
8 Study of NTBC for Tyrosinemia I Completed NCT00004443 Not Applicable NTBC
9 Biomarker for the Early Diagnosis and Monitoring in Tyrosinemia Type 1 Recruiting NCT03284658
10 Hereditary Hepatorenal Tyrosinemia Natural History in Egypt and the Arab World (Multicenter Clinical Study) Recruiting NCT03446586
11 Long Term Safety Study of Orfadin Treatment in HT-1 Patients in Standard Clinical Care Recruiting NCT02320084 Nitisinone

Search 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 30 HPD

Anatomical Context for Tyrosinemia, Type Iii

MalaCards organs/tissues related to Tyrosinemia, Type Iii:

42
Kidney, Bone, Neutrophil

Publications for Tyrosinemia, Type Iii

Articles related to Tyrosinemia, Type Iii:

# Title Authors Year
1
Markers of cognitive function in individuals with metabolic disease: Morquio syndrome and tyrosinemia type III. ( 29741470 )
2018
2
A Case of Tyrosinemia Type III with Status Epilepticus and Mental Retardation. ( 29456978 )
2018
3
Tyrosinemia type III in an asymptomatic girl. ( 28649543 )
2015
4
Tyrosinemia Type III detected via neonatal screening: management and outcome. ( 23036342 )
2012
5
Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III. ( 18657947 )
2009
6
Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. ( 11073718 )
2000
7
Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. ( 10942115 )
2000
8
Tyrosinemia type III: diagnosis and ten-year follow-up. ( 9343288 )
1997
9
Chronic tyrosinemia associated with 4-hydroxyphenylpyruvate dioxygenase deficiency with acute intermittent ataxia and without visceral and bone involvement. ( 6132360 )
1983

Variations for Tyrosinemia, Type Iii

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

76
# 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

ClinVar genetic disease variations for Tyrosinemia, Type Iii:

6 (show all 40)
# Gene Variation Type Significance SNP ID Assembly Location
1 HPD NM_001171993.1(HPD): c.362A> G (p.Tyr121Cys) single nucleotide variant Pathogenic rs137852865 GRCh37 Chromosome 12, 122287632: 122287632
2 HPD NM_001171993.1(HPD): c.362A> G (p.Tyr121Cys) single nucleotide variant Pathogenic rs137852865 GRCh38 Chromosome 12, 121849726: 121849726
3 HPD NM_001171993.1(HPD): c.657T> G (p.Tyr219Ter) single nucleotide variant Pathogenic rs137852866 GRCh37 Chromosome 12, 122284825: 122284825
4 HPD NM_001171993.1(HPD): c.657T> G (p.Tyr219Ter) single nucleotide variant Pathogenic rs137852866 GRCh38 Chromosome 12, 121846919: 121846919
5 HPD NM_001171993.1(HPD): c.483C> G (p.Tyr161Ter) single nucleotide variant Pathogenic rs137852867 GRCh37 Chromosome 12, 122285117: 122285117
6 HPD NM_001171993.1(HPD): c.483C> G (p.Tyr161Ter) single nucleotide variant Pathogenic rs137852867 GRCh38 Chromosome 12, 121847211: 121847211
7 HPD NM_002150.2(HPD): c.1005C> G (p.Ile335Met) single nucleotide variant Likely benign rs137852868 GRCh37 Chromosome 12, 122277904: 122277904
8 HPD NM_002150.2(HPD): c.1005C> G (p.Ile335Met) single nucleotide variant Likely benign rs137852868 GRCh38 Chromosome 12, 121839998: 121839998
9 HPD NM_002150.2(HPD): c.97G> A (p.Ala33Thr) single nucleotide variant Benign rs1154510 GRCh37 Chromosome 12, 122295335: 122295335
10 HPD NM_002150.2(HPD): c.97G> A (p.Ala33Thr) single nucleotide variant Benign rs1154510 GRCh38 Chromosome 12, 121857429: 121857429
11 HPD NM_002150.2(HPD): c.414G> A (p.Thr138=) single nucleotide variant Benign rs140788110 GRCh37 Chromosome 12, 122292609: 122292609
12 HPD NM_002150.2(HPD): c.414G> A (p.Thr138=) single nucleotide variant Benign rs140788110 GRCh38 Chromosome 12, 121854703: 121854703
13 HPD NM_002150.2(HPD): c.1018G> T (p.Val340Leu) single nucleotide variant Benign/Likely benign rs36023382 GRCh37 Chromosome 12, 122277891: 122277891
14 HPD NM_002150.2(HPD): c.1018G> T (p.Val340Leu) single nucleotide variant Benign/Likely benign rs36023382 GRCh38 Chromosome 12, 121839985: 121839985
15 HPD NM_002150.2(HPD): c.338G> A (p.Arg113Gln) single nucleotide variant Benign rs11833399 GRCh37 Chromosome 12, 122292685: 122292685
16 HPD NM_002150.2(HPD): c.338G> A (p.Arg113Gln) single nucleotide variant Benign rs11833399 GRCh38 Chromosome 12, 121854779: 121854779
17 HPD NM_002150.2(HPD): c.813C> T (p.Thr271=) single nucleotide variant Benign rs144416002 GRCh37 Chromosome 12, 122284786: 122284786
18 HPD NM_002150.2(HPD): c.813C> T (p.Thr271=) single nucleotide variant Benign rs144416002 GRCh38 Chromosome 12, 121846880: 121846880
19 HPD NM_002150.2(HPD): c.499G> A (p.Asp167Asn) single nucleotide variant Benign/Likely benign rs74820788 GRCh37 Chromosome 12, 122287612: 122287612
20 HPD NM_002150.2(HPD): c.499G> A (p.Asp167Asn) single nucleotide variant Benign/Likely benign rs74820788 GRCh38 Chromosome 12, 121849706: 121849706
21 HPD NC_000012.12: g.(?_121843690)_(121847234_?)del deletion Pathogenic GRCh38 Chromosome 12, 121843690: 121847234
22 HPD NC_000012.12: g.(?_121843690)_(121847234_?)del deletion Pathogenic GRCh37 Chromosome 12, 122281596: 122285140
23 HPD NM_002150.2(HPD): c.760-7C> T single nucleotide variant Likely benign rs748133768 GRCh37 Chromosome 12, 122284846: 122284846
24 HPD NM_002150.2(HPD): c.760-7C> T single nucleotide variant Likely benign rs748133768 GRCh38 Chromosome 12, 121846940: 121846940
25 HPD NM_002150.2(HPD): c.109T> C (p.Cys37Arg) single nucleotide variant Uncertain significance rs1246785384 GRCh37 Chromosome 12, 122295323: 122295323
26 HPD NM_002150.2(HPD): c.109T> C (p.Cys37Arg) single nucleotide variant Uncertain significance rs1246785384 GRCh38 Chromosome 12, 121857417: 121857417
27 HPD NC_000012.12: g.(?_121839708)_(121840068_?)del deletion Uncertain significance GRCh38 Chromosome 12, 121839708: 121840068
28 HPD NC_000012.12: g.(?_121839708)_(121840068_?)del deletion Uncertain significance GRCh37 Chromosome 12, 122277614: 122277974
29 HPD NM_002150.2(HPD): c.1151delT (p.Met384Argfs) deletion Uncertain significance rs1555339247 GRCh37 Chromosome 12, 122277665: 122277665
30 HPD NM_002150.2(HPD): c.1151delT (p.Met384Argfs) deletion Uncertain significance rs1555339247 GRCh38 Chromosome 12, 121839759: 121839759
31 HPD NM_002150.2(HPD): c.345C> T (p.Ala115=) single nucleotide variant Benign rs59741465 GRCh37 Chromosome 12, 122292678: 122292678
32 HPD NM_002150.2(HPD): c.345C> T (p.Ala115=) single nucleotide variant Benign rs59741465 GRCh38 Chromosome 12, 121854772: 121854772
33 HPD NM_002150.2(HPD): c.75G> A (p.Trp25Ter) single nucleotide variant Pathogenic rs367674632 GRCh37 Chromosome 12, 122295681: 122295681
34 HPD NM_002150.2(HPD): c.75G> A (p.Trp25Ter) single nucleotide variant Pathogenic rs367674632 GRCh38 Chromosome 12, 121857775: 121857775
35 HPD NM_002150.2(HPD): c.544G> A (p.Asp182Asn) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 121849051: 121849051
36 HPD NM_002150.2(HPD): c.544G> A (p.Asp182Asn) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 122286957: 122286957
37 HPD NM_002150.2(HPD): c.43C> T (p.Arg15Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 12, 121857807: 121857807
38 HPD NM_002150.2(HPD): c.43C> T (p.Arg15Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 12, 122295713: 122295713
39 HPD NM_002150.2(HPD): c.485C> T (p.Ala162Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 121849720: 121849720
40 HPD NM_002150.2(HPD): c.485C> T (p.Ala162Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 122287626: 122287626

Expression for Tyrosinemia, Type Iii

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

Pathways for Tyrosinemia, Type Iii

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 FAH GALNS HNRNPA2B1 HPD

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

# Name GO ID Score Top Affiliating Genes
1 L-phenylalanine catabolic process GO:0006559 9.33 FAH HPD TAT
2 aromatic amino acid family metabolic process GO:0009072 9.13 FAH HPD TAT
3 tyrosine catabolic process GO:0006572 8.8 FAH HPD TAT

Sources for Tyrosinemia, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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