Tyrosinemia, Type Iii

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

Aliases & Classifications for Tyrosinemia, Type Iii

MalaCards integrated aliases for Tyrosinemia, Type Iii:

Name: Tyrosinemia, Type Iii 53 13 69
Tyrosinemia Type Iii 12 49 55 71 14
4-Hydroxyphenylpyruvate Dioxygenase Deficiency 53 49 71 28
4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 53 71
Tyrosinemia Type 3 49 55
Tyrsn3 53 71
Tyrosinemia Due to 4-Hydroxyphenylpyruvate Dioxygenase Deficiency 55
Tyrosinemia Due to 4-Hydroxyphenylpyruvic Acid Oxidase Deficiency 55
4-Alpha Hydroxyphenylpyruvate Dioxygenase Deficiency 49
4-Alpha Hydroxyphenylpyruvic Acid Oxidase Deficiency 49
4-Hydroxyphenylpyruvate Dioxygenase 13
Tyrosinemia Due to Hpd Deficiency 55
Tyrosinemia 3 71


Orphanet epidemiological data:

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


autosomal recessive

allelic to hawkinsinuria


tyrosinemia, type iii:
Inheritance autosomal recessive inheritance


Orphanet: 55  
Inborn errors of metabolism

External Ids:

OMIM 53 276710
Disease Ontology 12 DOID:0050727
Orphanet 55 ORPHA69723
UMLS via Orphanet 70 C0268623
ICD10 via Orphanet 33 E70.2
MedGen 39 C0268623
MeSH 41 D020176
UMLS 69 C0268623

Summaries for Tyrosinemia, Type Iii

NIH Rare Diseases : 49 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. Last updated: 2/3/2010

MalaCards based summary : Tyrosinemia, Type Iii, also known as tyrosinemia type iii, is related to tyrosinemia and hawkinsinuria, and has symptoms including seizures, intellectual disability, mild and abnormality of the liver. 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 and neutrophil.

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

OMIM : 53 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 : 71 Tyrosinemia 3: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild mental retardation.

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 29.1 FAH HPD TAT
2 hawkinsinuria 9.8
3 tyrosinemia, type ii 9.6 FAH TAT
4 alkaptonuria 9.5 FAH HPD
5 tyrosinemia, type i 9.4 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:

Abdomen Liver:
normal liver function

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

Neurologic Central Nervous System:
mental retardation, mild

Clinical features from OMIM:


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 hypertyrosinemia 31 HP:0003231
6 4-hydroxyphenylacetic aciduria 31 HP:0003607

UMLS symptoms related to Tyrosinemia, Type Iii:


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
Nitisinone Approved, Investigational Phase 3,Phase 2,Phase 1 104206-65-7 115355

Interventional clinical trials:

(show all 11)

# Name Status NCT ID Phase Drugs
1 Efficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Nitisinone in HT-1 Completed NCT02323529 Phase 3 Nitisinone
2 Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria Active, not recruiting NCT01390077 Phase 2, 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 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 Enrolling by invitation 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 28 HPD

Anatomical Context for Tyrosinemia, Type Iii

MalaCards organs/tissues related to Tyrosinemia, Type Iii:

Liver, Neutrophil

Publications for Tyrosinemia, Type Iii

Articles related to Tyrosinemia, Type Iii:

# Title Authors Year
Tyrosinemia Type III detected via neonatal screening: management and outcome. ( 23036342 )
Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III. ( 18657947 )
Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. ( 11073718 )
Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. ( 10942115 )
Tyrosinemia type III: diagnosis and ten-year follow-up. ( 9343288 )

Variations for Tyrosinemia, Type Iii

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

# 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:

# 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.657T> G (p.Tyr219Ter) single nucleotide variant Pathogenic rs137852866 GRCh37 Chromosome 12, 122284825: 122284825
3 HPD NM_001171993.1(HPD): c.483C> G (p.Tyr161Ter) single nucleotide variant Pathogenic rs137852867 GRCh37 Chromosome 12, 122285117: 122285117

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

9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
51 Novoseek
54 OMIM via Orphanet
58 PubMed
66 SNOMED-CT via Orphanet
68 Tocris
70 UMLS via Orphanet
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