TYRSN2
MCID: TYR013
MIFTS: 46

Tyrosinemia, Type Ii (TYRSN2)

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 Ii

MalaCards integrated aliases for Tyrosinemia, Type Ii:

Name: Tyrosinemia, Type Ii 56 13
Tyrosinemia Type Ii 12 52 58 73 54 15
Oculocutaneous Tyrosinemia 12 74 52 58 73
Tyrosinemia Type 2 52 58 29 6 39
Richner-Hanhart Syndrome 56 12 58 73
Keratosis Palmoplantaris with Corneal Dystrophy 56 52 73
Tyrosine Aminotransferase Deficiency 56 52 73
Tyrosine Transaminase Deficiency 56 52 73
Tat Deficiency 56 52 73
Tyrosinosis Oculocutaneous Type 52 73
Oregon Type Tyrosinemia 56 52
Tyrsn2 56 73
Tyrosinemia Due to Tyrosine Aminotransferase Deficiency 58
Keratosis Palmoplantaris-Corneal Dystrophy Syndrome 58
Tyrosine Transaminase Deficiency Disease 71
Tyrosinemia Due to Tat Deficiency 58
Tyrosinosis, Oculocutaneous Type 56
Richner Hanhart Syndrome 52
Tyrosinemia Oregon Type 73
Tyrosinemia 2 73

Characteristics:

Orphanet epidemiological data:

58
tyrosinemia type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
tyrosinemia, type ii:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare skin diseases
Inborn errors of metabolism


Summaries for Tyrosinemia, Type Ii

NIH Rare Diseases : 52 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.

MalaCards based summary : Tyrosinemia, Type Ii, also known as tyrosinemia type ii, is related to tyrosinemia and keratosis. An important gene associated with Tyrosinemia, Type Ii is TAT (Tyrosine Aminotransferase), and among its related pathways/superpathways are Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism and Amino Acid metabolism. Affiliated tissues include liver, skin and eye, and related phenotypes are intellectual disability and corneal opacity

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 : 56 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 : 73 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 : 74 Tyrosinemia type II is an autosomal recessive condition with onset between ages 2 and 4 years, when... more...

Related Diseases for Tyrosinemia, Type Ii

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



Diseases related to Tyrosinemia, Type Ii

Symptoms & Phenotypes for Tyrosinemia, Type Ii

Human phenotypes related to Tyrosinemia, Type Ii:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 corneal opacity 58 31 hallmark (90%) Very frequent (99-80%) HP:0007957
3 palmoplantar keratoderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0000982
4 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
5 hyperhidrosis 58 31 frequent (33%) Frequent (79-30%) HP:0000975
6 abnormality of amino acid metabolism 58 31 frequent (33%) Frequent (79-30%) HP:0004337
7 photophobia 58 31 frequent (33%) Frequent (79-30%) HP:0000613
8 malar flattening 58 31 occasional (7.5%) Occasional (29-5%) HP:0000272
9 seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0001250
10 neurological speech impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0002167
11 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
12 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
13 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
14 abnormality of the nail 58 31 occasional (7.5%) Occasional (29-5%) HP:0001597
15 visual loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0000572
16 behavioral abnormality 58 Frequent (79-30%)
17 hyperkeratosis 58 Very frequent (99-80%)
18 growth delay 31 HP:0001510
19 abnormality of the skin 31 HP:0000951
20 4-hydroxyphenylpyruvic aciduria 31 HP:0003161
21 herpetiform corneal ulceration 31 HP:0007812
22 hypertyrosinemia 31 HP:0003231

Symptoms via clinical synopsis from OMIM:

56
Growth:
growth retardation

Eyes:
herpetiform corneal ulcers

Lab:
tyrosinemia
tyrosine transaminase deficiency
normal p-hydroxyphenylpyruvic acid oxidase
normal phenylalanine level
hydroxyphenylpyruvic aciduria
more
Neuro:
mental retardation

Skin:
painful punctate keratoses of digits, palms, and soles

Clinical features from OMIM:

276600

Drugs & Therapeutics for Tyrosinemia, Type Ii

Search Clinical Trials , 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 29 TAT

Anatomical Context for Tyrosinemia, Type Ii

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

19
Liver

MalaCards organs/tissues related to Tyrosinemia, Type Ii:

40
Skin, Liver, Eye, Brain, Cortex

Publications for Tyrosinemia, Type Ii

Articles related to Tyrosinemia, Type Ii:

(show top 50) (show all 81)
# Title Authors PMID Year
1
Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. 61 56 6
1357662 1992
2
The human tyrosine aminotransferase gene: characterization of restriction fragment length polymorphisms and haplotype analysis in a family with tyrosinemia type II. 61 56
2456982 1988
3
Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1----q22.3 in a patient with tyrosinemia type II. 61 56
2891604 1987
4
Richner-Hanhart syndrome and tyrosinemia type II. 61 56
6446465 1980
5
Pregnancy and tyrosinaemia type II. 56
12227462 2002
6
Richner-Hanhart syndrome: importance of early diagnosis and early intervention. 56
8912606 1996
7
Hereditary tyrosinaemia type II in a consanguineous Ashkenazi Jewish family: intrafamilial variation in phenotype; absence of parental phenotype effects on the fetus. 56
1356171 1992
8
Assignment of the human tyrosine aminotransferase gene to chromosome 16. 56
2870018 1986
9
Richner-Hanhart syndrome spares a plantar autograft. 56
3156564 1985
10
Richner-Hanhart's syndrome: ultrastructural abnormalities of epidermal keratinization indicating a causal relationship to high intracellular tyrosine levels. 56
6124575 1982
11
Richner-Hanhart syndrome (tyrosinaemia-II) (report of four cases without ocular involvement). 56
6453606 1981
12
Tyrosinemia without liver or renal damage with plantar and palmar keratosis and keratitis (hypertyrosinemia type II). 56
156708 1979
13
Oculocutaneous tyrosinosis. Report of two cases in the same family. 56
33934 1977
14
The Richner-Hanhart syndrome: report of a case with associated tyrosinemia. 56
180943 1976
15
Tyrosinemia with plantar and palmar keratosis and keratitis. 56
4270265 1973
16
Soluble and mitochondrial forms of tyrosine aminotransferase. Relationship to human tyrosinemia. 56
4389443 1969
17
[Keratoma palmoplantar dissipatum associated with corneal lesions in 2 siblings]. 56
5880823 1965
18
[Not Available]. 56
18901242 1947
19
Tyrosine administration decreases glutathione and stimulates lipid and protein oxidation in rat cerebral cortex. 54 61
19688254 2009
20
Corneal lesion as the initial manifestation of tyrosinemia type II. 54 61
16863017 2006
21
Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations. 54 61
16574453 2006
22
The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. 54 61
16640556 2006
23
The genetic tyrosinemias. 54 61
16602095 2006
24
Comparison of the tyrosine aminotransferase cDNA and genomic DNA sequences of normal mink and mink affected with tyrosinemia type II. 54 61
15817712 2005
25
[Tyrosinemia type II. Case report]. 54 61
16050420 2005
26
Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type II. 54 61
9544843 1998
27
Effects of omega-3 fatty acids supplementation on inflammatory parameters after chronic administration of L-tyrosine. 61
31828693 2020
28
Evidence of hippocampal astrogliosis and antioxidant imbalance after L-tyrosine chronic administration in rats. 61
31705440 2020
29
Whole-exome sequencing identifies a homozygous pathogenic variant in TAT in a girl with palmoplantar keratoderma. 61
31799120 2019
30
Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats. 61
30949952 2019
31
Antioxidants Reverse the Changes in the Cholinergic System Caused by L-Tyrosine Administration in Rats. 61
29417439 2018
32
[Corneal involvement in tyrosinemia type II mimicking herpetic keratitis: Case report in an adult]. 61
30126694 2018
33
Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options. 61
29094226 2018
34
Richner-Hanhart syndrome (tyrosinemia type II). 61
29360903 2017
35
Role of antioxidant treatment on DNA and lipid damage in the brain of rats subjected to a chemically induced chronic model of tyrosinemia type II. 61
28547180 2017
36
Tyrosinemia type II: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation. 61
28255985 2017
37
Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II. 61
28315992 2017
38
Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome. 61
27832414 2017
39
Palmoplantar hyperkeratosis with a linear disposition along dermatoglyphics: a clue for an early diagnosis of tyrosinemia type II. 61
28166616 2017
40
Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L.-tyrosine. 61
27924409 2017
41
Investigation of Fibril Forming Mechanisms of l-Phenylalanine and l-Tyrosine: Microscopic Insight toward Phenylketonuria and Tyrosinemia Type II. 61
28121442 2017
42
Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation. 61
27285949 2016
43
Olmsted syndrome: clinical, molecular and therapeutic aspects. 61
25886873 2015
44
The characterization of neuroenergetic effects of chronic L-tyrosine administration in young rats: evidence for striatal susceptibility. 61
25252880 2015
45
Creatine and pyruvate prevent the alterations caused by tyrosine on parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex of Wistar rats. 61
24961569 2015
46
In vivo confocal microscopic features of corneal pseudodendritic lesions in tyrosinemia type II. 61
25119963 2014
47
An evaluation of the effects of acute and chronic L-tyrosine administration on BDNF levels and BDNF mRNA expression in the rat brain. 61
24091827 2014
48
L-tyrosine induces DNA damage in brain and blood of rats. 61
24297753 2014
49
Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats. 61
24135880 2013
50
Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome. 61
23954227 2013

Variations for Tyrosinemia, Type Ii

ClinVar genetic disease variations for Tyrosinemia, Type Ii:

6 (show all 28) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TAT NM_000353.3(TAT):c.668C>G (p.Ser223Ter)SNV Pathogenic 403 rs118203915 16:71606127-71606127 16:71572224-71572224
2 TAT NM_000353.3(TAT):c.1249C>T (p.Arg417Ter)SNV Pathogenic 404 rs118203916 16:71602163-71602163 16:71568260-71568260
3 TAT NM_000353.3(TAT):c.1085G>T (p.Gly362Val)SNV Pathogenic 405 rs587776511 16:71603797-71603797 16:71569894-71569894
4 TAT NM_000353.3(TAT):c.236-5A>GSNV Pathogenic 406 rs587776512 16:71609934-71609934 16:71576031-71576031
5 TAT NM_000353.3(TAT):c.169C>T (p.Arg57Ter)SNV Pathogenic/Likely pathogenic 402 rs118203914 16:71610150-71610150 16:71576247-71576247
6 TAT NM_000353.3(TAT):c.226dup (p.Leu76fs)duplication Likely pathogenic 550810 rs746077579 16:71610092-71610093 16:71576189-71576190
7 TAT NM_000353.3(TAT):c.1297C>T (p.Arg433Trp)SNV Likely pathogenic 553180 rs761817519 16:71602115-71602115 16:71568212-71568212
8 TAT NM_000353.3(TAT):c.340G>A (p.Gly114Ser)SNV Likely pathogenic 432087 rs759311161 16:71609825-71609825 16:71575922-71575922
9 TAT NM_000353.3(TAT):c.177dup (p.Val60fs)duplication Likely pathogenic 557491 rs1555538156 16:71610141-71610142 16:71576238-71576239
10 TAT NM_000353.3(TAT):c.1A>G (p.Met1Val)SNV Likely pathogenic 553670 rs1426882225 16:71610318-71610318 16:71576415-71576415
11 TAT NM_000353.3(TAT):c.1041+2T>CSNV Likely pathogenic 553223 rs113758103 16:71604170-71604170 16:71570267-71570267
12 TAT NM_000353.3(TAT):c.906_912+12deldeletion Likely pathogenic 554092 rs1555537741 16:71604570-71604588 16:71570667-71570685
13 TAT NM_000353.3(TAT):c.707-1G>ASNV Likely pathogenic 550032 rs1555537814 16:71605562-71605562 16:71571659-71571659
14 TAT NM_000353.3(TAT):c.1125+1G>TSNV Likely pathogenic 552384 rs1555537662 16:71603756-71603756 16:71569853-71569853
15 TAT NM_000353.3(TAT):c.568-2A>GSNV Likely pathogenic 552516 rs1555537871 16:71606229-71606229 16:71572326-71572326
16 TAT NM_000353.3(TAT):c.340+2T>CSNV Likely pathogenic 550551 rs1555538138 16:71609823-71609823 16:71575920-71575920
17 TAT NM_000353.3(TAT):c.235+1G>ASNV Likely pathogenic 552449 rs748924248 16:71610083-71610083 16:71576180-71576180
18 TAT NM_000353.3(TAT):c.1047del (p.Asn349fs)deletion Likely pathogenic 553660 rs1555537673 16:71603835-71603835 16:71569932-71569932
19 TAT NM_000353.3(TAT):c.1298G>A (p.Arg433Gln)SNV Conflicting interpretations of pathogenicity 550347 rs775488556 16:71602114-71602114 16:71568211-71568211
20 TAT NM_000353.3(TAT):c.1224G>A (p.Thr408=)SNV Uncertain significance 550922 rs756743947 16:71602614-71602614 16:71568711-71568711
21 TAT NM_000353.3(TAT):c.1363T>C (p.Ter455Gln)SNV Uncertain significance 553920 rs1018491678 16:71602049-71602049 16:71568146-71568146
22 TAT NM_000353.3(TAT):c.1250G>A (p.Arg417Gln)SNV Uncertain significance 550062 rs757879229 16:71602162-71602162 16:71568259-71568259
23 TAT NM_000353.3(TAT):c.-12-1G>ASNV Uncertain significance 551655 rs777389158 16:71610331-71610331 16:71576428-71576428
24 TAT NM_000353.3(TAT):c.1223C>T (p.Thr408Met)SNV Uncertain significance 551483 rs200815080 16:71602615-71602615 16:71568712-71568712
25 TAT NM_000353.3(TAT):c.355C>T (p.Arg119Trp)SNV Uncertain significance 550997 rs758306831 16:71607495-71607495 16:71573592-71573592
26 TAT NM_000353.3(TAT):c.863_874del (p.Arg288_Trp291del)deletion Uncertain significance 590839 rs1567590737 16:71604620-71604631 16:71570717-71570728
27 TAT NM_000353.3(TAT):c.716G>A (p.Arg239Gln)SNV Uncertain significance 665181 16:71605552-71605552 16:71571649-71571649
28 TAT NM_000353.3(TAT):c.578C>A (p.Ser193Tyr)SNV Uncertain significance 665810 16:71606217-71606217 16:71572314-71572314

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

73
# Symbol AA change Variation ID SNP ID
1 TAT p.Gly362Val VAR_000560 rs587776511

Cosmic variations for Tyrosinemia, Type Ii:

9
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM112988963 HRAS skin,hand,other,keratosis c.35G>A p.G12D 11:534288-534288 3
2 COSM101967369 skin,hand,other,keratosis c.35G>A p.G12D 11:534288-534288 3
3 COSM105721529 skin,hand,other,keratosis c.35G>A p.G12D 11:534288-534288 3
4 COSM91331287 skin,hand,other,keratosis c.35G>A p.G12D 11:534288-534288 3
5 COSM101951730 skin,hand,other,keratosis c.35G>A p.G12D 11:534288-534288 3

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 cellular amino acid metabolic process GO:0006520 9.26 TAT HGD
2 aromatic amino acid family metabolic process GO:0009072 9.16 TAT FAH
3 L-phenylalanine catabolic process GO:0006559 9.13 TAT HGD FAH
4 tyrosine catabolic process GO:0006572 8.8 TAT HGD FAH

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

# Name GO ID Score Top Affiliating Genes
1 transcription regulatory region DNA binding GO:0044212 8.8 ZNF821 ZFHX3 TP63

Sources for Tyrosinemia, Type Ii

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
Content
Loading form....