MCID: TYR013
MIFTS: 45

Tyrosinemia, Type Ii

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

Aliases & Classifications for Tyrosinemia, Type Ii

MalaCards integrated aliases for Tyrosinemia, Type Ii:

Name: Tyrosinemia, Type Ii 53 13
Tyrosinemia Type Ii 12 49 55 71 51 14
Oculocutaneous Tyrosinemia 12 72 49 55 71
Richner-Hanhart Syndrome 53 12 55 71
Keratosis Palmoplantaris with Corneal Dystrophy 53 49 71
Tyrosine Aminotransferase Deficiency 53 49 71
Tyrosine Transaminase Deficiency 53 49 71
Tyrosinemia Type 2 49 55 28
Tat Deficiency 53 49 71
Tyrosinosis Oculocutaneous Type 49 71
Oregon Type Tyrosinemia 53 49
Tyrsn2 53 71
Tyrosinemia Due to Tyrosine Aminotransferase Deficiency 55
Keratosis Palmoplantaris-Corneal Dystrophy Syndrome 55
Tyrosine Transaminase Deficiency Disease 69
Tyrosinemia Due to Tat Deficiency 55
Tyrosinosis, Oculocutaneous Type 53
Richner Hanhart Syndrome 49
Tyrosinemia Oregon Type 71
Tyrosinemia 2 71

Characteristics:

Orphanet epidemiological data:

55
tyrosinemia type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
tyrosinemia, type ii:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 276600
Disease Ontology 12 DOID:0050725
Orphanet 55 ORPHA28378
UMLS via Orphanet 70 C0268487
ICD10 via Orphanet 33 E70.2
MedGen 39 C0268487
MeSH 41 D020176
UMLS 69 C0268487

Summaries for Tyrosinemia, Type Ii

NIH Rare Diseases : 49 Tyrosinemia type 2 is a genetic disorder in which individuals have elevated blood levels of the amino acid tyrosine, a building block of most proteins. This condition can affect the eyes, skin, and intellectual development. Symptoms of tyrosinemia type 2 often begin in early childhood and include excessive tearing, abnormal sensitivity to light (photophobia), eye pain and redness, and painful skin lesions on the palms and soles (palmoplantar hyperkeratosis). About 50 percent of individuals with this condition have an intellectual disability. Tyrosinemia type 2 is caused by a deficiency of the enzyme tyrosine aminotransferase, one of the enzymes required for the multi-step process that breaks down tyrosine. This enzyme shortage is caused by mutations in the TAT gene. This condition is inherited in an autosomal recessive manner. There is no cure for this condition; however, some of the symptoms may be managed with a diet that limits certain amino acids, such as phenylalanine and tyrosine. A medication called NTBC may also be used to help control the amount of tyrosine in the body. Last updated: 5/24/2017

MalaCards based summary : Tyrosinemia, Type Ii, also known as tyrosinemia type ii, is related to tyrosinemia and blood group, i system, and has symptoms including abnormality of the skin, intellectual disability and growth delay. An important gene associated with Tyrosinemia, Type Ii is TAT (Tyrosine Aminotransferase), and among its related pathways/superpathways are Carbon 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 the liver, skin and liver.

Disease Ontology : 12 A tyrosinemia that has material basis in deficiency of hepatic tyrosine aminotransferase located in the liver and is characterized by keratitis, painful palmoplantar hyperkeratosis, mental retardation, and elevated serum tyrosine levels.

OMIM : 53 Tyrosinemia type II is an autosomal recessive disorder characterized by keratitis, painful palmoplantar hyperkeratosis, mental retardation, and elevated serum tyrosine levels. The disorder is caused by deficiency of hepatic tyrosine aminotransferase (Natt et al., 1992). (276600)

UniProtKB/Swiss-Prot : 71 Tyrosinemia 2: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and oculocutaneous manifestations. Typical features include palmoplantar keratosis, painful corneal ulcers, and mental retardation.

Wikipedia : 72 Tyrosinemia type II (Oculocutaneous tyrosinemia,Richner-Hanhart syndrome) is an autosomal recessive... more...

Related Diseases for Tyrosinemia, Type Ii

Diseases in the Tyrosinemia family:

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

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

# Related Disease Score Top Affiliating Genes
1 tyrosinemia 30.2 FAH TAT
2 blood group, i system 10.4
3 hanhart syndrome 10.2
4 episodic pain syndrome, familial, 1 9.9
5 tyrosinemia, type iii 9.9 FAH TAT
6 ifap syndrome with or without bresheck syndrome 9.8
7 hepatitis 9.8
8 limbal stem cell deficiency 9.5 KRT12 TP63

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



Diseases related to Tyrosinemia, Type Ii

Symptoms & Phenotypes for Tyrosinemia, Type Ii

Symptoms via clinical synopsis from OMIM:

53
Eyes:
herpetiform corneal ulcers

Neuro:
mental retardation

Lab:
tyrosinemia
tyrosine transaminase deficiency
normal p-hydroxyphenylpyruvic acid oxidase
normal phenylalanine level
hydroxyphenylpyruvic aciduria
more
Skin:
painful punctate keratoses of digits, palms, and soles

Growth:
growth retardation


Clinical features from OMIM:

276600

Human phenotypes related to Tyrosinemia, Type Ii:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 abnormality of the skin 31 HP:0000951
2 intellectual disability 31 HP:0001249
3 growth delay 31 HP:0001510
4 4-hydroxyphenylpyruvic aciduria 31 HP:0003161
5 hypertyrosinemia 31 HP:0003231
6 herpetiform corneal ulceration 31 HP:0007812

Drugs & Therapeutics for Tyrosinemia, Type Ii

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
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 Ii

Genetic Tests for Tyrosinemia, Type Ii

Genetic tests related to Tyrosinemia, Type Ii:

# Genetic test Affiliating Genes
1 Tyrosinemia Type 2 28 TAT

Anatomical Context for Tyrosinemia, Type Ii

The Foundational Model of Anatomy Ontology organs/tissues related to Tyrosinemia, Type Ii:

18
The Liver

MalaCards organs/tissues related to Tyrosinemia, Type Ii:

38
Skin, Liver, Eye

Publications for Tyrosinemia, Type Ii

Articles related to Tyrosinemia, Type Ii:

(show all 28)
# Title Authors Year
1
Richner-Hanhart syndrome (tyrosinemia type II). ( 29360903 )
2017
2
Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation. ( 27285949 )
2016
3
In vivo confocal microscopic features of corneal pseudodendritic lesions in tyrosinemia type II. ( 25119963 )
2014
4
Isolated corneal pseudodendrites as the initial manifestation of tyrosinemia type II in monozygotic twins. ( 22588828 )
2012
5
Tyrosinemia type II (Richner-Hanhart syndrome): a new mutation in the TAT gene. ( 21145993 )
2011
6
Richner-Hanhart syndrome (tyrosinemia type II): a case report of delayed diagnosis with pseudodendritic corneal lesion. ( 22389994 )
2011
7
The narrow substrate specificity of human tyrosine aminotransferase -- the enzyme deficient in tyrosinemia type II. ( 16640556 )
2006
8
Corneal lesion as the initial manifestation of tyrosinemia type II. ( 16863017 )
2006
9
Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations. ( 16574453 )
2006
10
Comparison of the tyrosine aminotransferase cDNA and genomic DNA sequences of normal mink and mink affected with tyrosinemia type II. ( 15817712 )
2005
11
[Tyrosinemia type II. Case report]. ( 16050420 )
2005
12
Plantar keratoderma: a manifestation of tyrosinemia type II (Richner-Hanhart syndrome). ( 16270769 )
2005
13
Tyrosinemia type II: nine cases of ocular signs and symptoms. ( 11589874 )
2001
14
Tyrosinemia type II: Report of the first four cases in Saudi Arabia. ( 17344737 )
1998
15
Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type II. ( 9544843 )
1998
16
Tyrosinemia type II: a challenge for ophthalmologists and dermatologists. ( 9144695 )
1997
17
Painful keratoderma and photophobia: hallmarks of tyrosinemia type II. ( 7844676 )
1995
18
Richner-Hanhart syndrome (tyrosinemia type II). Case report and literature review. ( 7648039 )
1995
19
Painful plantar callouses and mental retardation. Tyrosinemia type II. ( 7909424 )
1994
20
Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. ( 1357662 )
1992
21
Early diagnosis of tyrosinemia type II. ( 2712144 )
1989
22
The human tyrosine aminotransferase gene: characterization of restriction fragment length polymorphisms and haplotype analysis in a family with tyrosinemia type II. ( 2456982 )
1988
23
Clinical picture and problems of keratoplasty in Richner-Hanhart syndrome (tyrosinemia type II). ( 3054681 )
1988
24
Tyrosinemia type II with incomplete Richner-Hanhart's syndrome. ( 2964425 )
1988
25
Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1----q22.3 in a patient with tyrosinemia type II. ( 2891604 )
1987
26
Tyrosinemia type II in two cases previously reported as Richner-Hanhart syndrome. ( 2947825 )
1986
27
New forms of hereditary tyrosinemia type II in mink: hepatic tyrosine aminotransferase defect. ( 2876972 )
1986
28
Richner-Hanhart syndrome and tyrosinemia type II. ( 6446465 )
1980

Variations for Tyrosinemia, Type Ii

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

71
# Symbol AA change Variation ID SNP ID
1 TAT p.Gly362Val VAR_000560 rs587776511

ClinVar genetic disease variations for Tyrosinemia, Type Ii:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TAT NM_000353.2(TAT): c.169C> T (p.Arg57Ter) single nucleotide variant Pathogenic rs118203914 GRCh37 Chromosome 16, 71610150: 71610150
2 TAT NM_000353.2(TAT): c.668C> G (p.Ser223Ter) single nucleotide variant Pathogenic rs118203915 GRCh37 Chromosome 16, 71606127: 71606127
3 TAT NM_000353.2(TAT): c.1249C> T (p.Arg417Ter) single nucleotide variant Pathogenic rs118203916 GRCh37 Chromosome 16, 71602163: 71602163
4 TAT NM_000353.2(TAT): c.1085G> T (p.Gly362Val) single nucleotide variant Pathogenic rs587776511 GRCh38 Chromosome 16, 71569894: 71569894
5 TAT NM_000353.2(TAT): c.236-5A> G single nucleotide variant Pathogenic rs587776512 GRCh38 Chromosome 16, 71576031: 71576031

Expression for Tyrosinemia, Type Ii

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

Pathways for Tyrosinemia, Type Ii

GO Terms for Tyrosinemia, Type Ii

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

# Name GO ID Score Top Affiliating Genes
1 response to glucocorticoid GO:0051384 9.26 CPS1 TAT
2 L-phenylalanine catabolic process GO:0006559 9.16 FAH TAT
3 aromatic amino acid family metabolic process GO:0009072 8.96 FAH TAT
4 tyrosine catabolic process GO:0006572 8.62 FAH TAT

Sources for Tyrosinemia, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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