MCID: TYR011
MIFTS: 42

Tyrosinemia, Type Iii

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

Aliases & Classifications for Tyrosinemia, Type Iii

MalaCards integrated aliases for Tyrosinemia, Type Iii:

Name: Tyrosinemia, Type Iii 57 13 40 73
4-Hydroxyphenylpyruvate Dioxygenase Deficiency 57 53 75 29 6
Tyrosinemia Type Iii 12 53 59 75 15
4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 57 75
Tyrosinemia Type 3 53 59
Tyrsn3 57 75
Tyrosinemia Due to 4-Hydroxyphenylpyruvate Dioxygenase Deficiency 59
Tyrosinemia Due to 4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 59
4-Alpha Hydroxyphenylpyruvate Dioxygenase Deficiency 53
4-Alpha Hydroxyphenylpyruvic Acid Oxidase Deficiency 53
4-Hydroxyphenylpyruvate Dioxygenase 13
Tyrosinemia Due to Hpd Deficiency 59
Tyrosinemia 3 75

Characteristics:

Orphanet epidemiological data:

59
tyrosinemia type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
allelic to hawkinsinuria


HPO:

32
tyrosinemia, type iii:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


External Ids:

OMIM 57 276710
Disease Ontology 12 DOID:0050727
Orphanet 59 ORPHA69723
UMLS via Orphanet 74 C0268623
ICD10 via Orphanet 34 E70.2
MedGen 42 C0268623
MeSH 44 D020176
UMLS 73 C0268623

Summaries for Tyrosinemia, Type Iii

NIH Rare Diseases : 53 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 hawkinsinuria, 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 liver, kidney and neutrophil, and related phenotypes are seizures and intellectual disability, mild

OMIM : 57 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 : 75 Tyrosinemia 3: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild mental retardation.

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

Wikipedia : 76 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:

# Related Disease Score Top Affiliating Genes
1 tyrosinemia 28.7 FAH HPD TAT
2 hawkinsinuria 9.8
3 status epilepticus 9.8
4 morquio syndrome 9.8
5 tyrosinemia, type ii 9.3 FAH TAT
6 alkaptonuria 9.3 FAH HPD
7 tyrosinemia, type i 9.1 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

Symptoms via clinical synopsis from OMIM:

57
Abdomen Liver:
normal liver function

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

Neurologic Central Nervous System:
mental retardation, mild
seizures


Clinical features from OMIM:

276710

Human phenotypes related to Tyrosinemia, Type Iii:

32 (show all 6)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 intellectual disability, mild 32 HP:0001256
3 abnormality of the liver 32 HP:0001392
4 4-hydroxyphenylpyruvic aciduria 32 HP:0003161
5 hypertyrosinemia 32 HP:0003231
6 4-hydroxyphenylacetic aciduria 32 HP:0003607

UMLS symptoms related to Tyrosinemia, Type Iii:


seizures

MGI Mouse Phenotypes related to Tyrosinemia, Type Iii:

46
# 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 Hereditary Hepatorenal Tyrosinemia Natural History in Egypt and the Arab World (Multicenter Clinical Study) Recruiting NCT03446586
10 Biomarker for the Early Diagnosis and Monitoring in Tyrosinemia Type 1 Recruiting NCT03284658
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 29 HPD

Anatomical Context for Tyrosinemia, Type Iii

MalaCards organs/tissues related to Tyrosinemia, Type Iii:

41
Liver, Kidney, Neutrophil, Bone

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 detected via neonatal screening: management and outcome. ( 23036342 )
2012
4
Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III. ( 18657947 )
2009
5
Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. ( 11073718 )
2000
6
Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. ( 10942115 )
2000
7
Tyrosinemia type III: diagnosis and ten-year follow-up. ( 9343288 )
1997
8
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:

75
# 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 30)
# 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.414G> A (p.Thr138=) single nucleotide variant Benign rs140788110 GRCh37 Chromosome 12, 122292609: 122292609
8 HPD NM_002150.2(HPD): c.414G> A (p.Thr138=) single nucleotide variant Benign rs140788110 GRCh38 Chromosome 12, 121854703: 121854703
9 HPD NM_002150.2(HPD): c.1018G> T (p.Val340Leu) single nucleotide variant Benign/Likely benign rs36023382 GRCh37 Chromosome 12, 122277891: 122277891
10 HPD NM_002150.2(HPD): c.1018G> T (p.Val340Leu) single nucleotide variant Benign/Likely benign rs36023382 GRCh38 Chromosome 12, 121839985: 121839985
11 HPD NM_002150.2(HPD): c.338G> A (p.Arg113Gln) single nucleotide variant Benign rs11833399 GRCh37 Chromosome 12, 122292685: 122292685
12 HPD NM_002150.2(HPD): c.338G> A (p.Arg113Gln) single nucleotide variant Benign rs11833399 GRCh38 Chromosome 12, 121854779: 121854779
13 HPD NM_002150.2(HPD): c.813C> T (p.Thr271=) single nucleotide variant Benign rs144416002 GRCh37 Chromosome 12, 122284786: 122284786
14 HPD NM_002150.2(HPD): c.813C> T (p.Thr271=) single nucleotide variant Benign rs144416002 GRCh38 Chromosome 12, 121846880: 121846880
15 HPD NM_002150.2(HPD): c.499G> A (p.Asp167Asn) single nucleotide variant Benign/Likely benign rs74820788 GRCh37 Chromosome 12, 122287612: 122287612
16 HPD NM_002150.2(HPD): c.499G> A (p.Asp167Asn) single nucleotide variant Benign/Likely benign rs74820788 GRCh38 Chromosome 12, 121849706: 121849706
17 HPD NC_000012.12: g.(?_121843690)_(121847234_?)del deletion Pathogenic GRCh38 Chromosome 12, 121843690: 121847234
18 HPD NC_000012.12: g.(?_121843690)_(121847234_?)del deletion Pathogenic GRCh37 Chromosome 12, 122281596: 122285140
19 HPD NM_002150.2(HPD): c.760-7C> T single nucleotide variant Likely benign rs748133768 GRCh38 Chromosome 12, 121846940: 121846940
20 HPD NM_002150.2(HPD): c.760-7C> T single nucleotide variant Likely benign rs748133768 GRCh37 Chromosome 12, 122284846: 122284846
21 HPD NM_002150.2(HPD): c.109T> C (p.Cys37Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 122295323: 122295323
22 HPD NM_002150.2(HPD): c.109T> C (p.Cys37Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 121857417: 121857417
23 HPD NC_000012.12: g.(?_121839708)_(121840068_?)del deletion Uncertain significance GRCh37 Chromosome 12, 122277614: 122277974
24 HPD NC_000012.12: g.(?_121839708)_(121840068_?)del deletion Uncertain significance GRCh38 Chromosome 12, 121839708: 121840068
25 HPD NM_002150.2(HPD): c.1151delT (p.Met384Argfs) deletion Uncertain significance GRCh38 Chromosome 12, 121839759: 121839759
26 HPD NM_002150.2(HPD): c.1151delT (p.Met384Argfs) deletion Uncertain significance GRCh37 Chromosome 12, 122277665: 122277665
27 HPD NM_002150.2(HPD): c.345C> T (p.Ala115=) single nucleotide variant Benign rs59741465 GRCh37 Chromosome 12, 122292678: 122292678
28 HPD NM_002150.2(HPD): c.345C> T (p.Ala115=) single nucleotide variant Benign rs59741465 GRCh38 Chromosome 12, 121854772: 121854772
29 HPD NM_002150.2(HPD): c.75G> A (p.Trp25Ter) single nucleotide variant Pathogenic rs367674632 GRCh37 Chromosome 12, 122295681: 122295681
30 HPD NM_002150.2(HPD): c.75G> A (p.Trp25Ter) single nucleotide variant Pathogenic rs367674632 GRCh38 Chromosome 12, 121857775: 121857775

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

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 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
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