MCID: TYR013
MIFTS: 46

Tyrosinemia, Type Ii

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

Aliases & Classifications for Tyrosinemia, Type Ii

MalaCards integrated aliases for Tyrosinemia, Type Ii:

Name: Tyrosinemia, Type Ii 57 13
Tyrosinemia Type Ii 12 53 59 75 55 15
Oculocutaneous Tyrosinemia 12 76 53 59 75
Tyrosinemia Type 2 53 59 29 6 40
Richner-Hanhart Syndrome 57 12 59 75
Keratosis Palmoplantaris with Corneal Dystrophy 57 53 75
Tyrosine Aminotransferase Deficiency 57 53 75
Tyrosine Transaminase Deficiency 57 53 75
Tat Deficiency 57 53 75
Tyrosinosis Oculocutaneous Type 53 75
Oregon Type Tyrosinemia 57 53
Tyrsn2 57 75
Tyrosinemia Due to Tyrosine Aminotransferase Deficiency 59
Keratosis Palmoplantaris-Corneal Dystrophy Syndrome 59
Tyrosine Transaminase Deficiency Disease 73
Tyrosinemia Due to Tat Deficiency 59
Tyrosinosis, Oculocutaneous Type 57
Richner Hanhart Syndrome 53
Tyrosinemia Oregon Type 75
Tyrosinemia 2 75

Characteristics:

Orphanet epidemiological data:

59
tyrosinemia type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
tyrosinemia, type ii:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Tyrosinemia, Type Ii

NIH Rare Diseases : 53 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 hanhart syndrome. 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, and related phenotypes are palmoplantar keratoderma and intellectual disability

OMIM : 57 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 : 75 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.

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.

Wikipedia : 76 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 29.9 FAH TAT
2 hanhart syndrome 10.3
3 hepatitis 9.8
4 tyrosinemia, type iii 9.8 FAH TAT
5 limbal stem cell deficiency 9.2 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:

57
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

Human phenotypes related to Tyrosinemia, Type Ii:

59 32 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 palmoplantar keratoderma 59 32 hallmark (90%) Very frequent (99-80%) HP:0000982
2 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
3 corneal opacity 59 32 hallmark (90%) Very frequent (99-80%) HP:0007957
4 photophobia 59 32 frequent (33%) Frequent (79-30%) HP:0000613
5 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
6 hyperhidrosis 59 32 frequent (33%) Frequent (79-30%) HP:0000975
7 abnormality of amino acid metabolism 59 32 frequent (33%) Frequent (79-30%) HP:0004337
8 microcephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000252
9 malar flattening 59 32 occasional (7.5%) Occasional (29-5%) HP:0000272
10 visual loss 59 32 occasional (7.5%) Occasional (29-5%) HP:0000572
11 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
12 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
13 tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0001337
14 abnormality of the nail 59 32 occasional (7.5%) Occasional (29-5%) HP:0001597
15 neurological speech impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0002167
16 hyperkeratosis 59 Very frequent (99-80%)
17 behavioral abnormality 59 Frequent (79-30%)
18 abnormality of the skin 32 HP:0000951
19 growth delay 32 HP:0001510
20 4-hydroxyphenylpyruvic aciduria 32 HP:0003161
21 hypertyrosinemia 32 HP:0003231
22 herpetiform corneal ulceration 32 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 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 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
The Liver

MalaCards organs/tissues related to Tyrosinemia, Type Ii:

41
Skin, Liver, Eye

Publications for Tyrosinemia, Type Ii

Articles related to Tyrosinemia, Type Ii:

(show all 29)
# Title Authors Year
1
Richner-Hanhart syndrome (tyrosinemia type II). ( 29360903 )
2017
2
Tyrosinemia type II: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation. ( 28255985 )
2017
3
Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation. ( 27285949 )
2016
4
In vivo confocal microscopic features of corneal pseudodendritic lesions in tyrosinemia type II. ( 25119963 )
2014
5
Isolated corneal pseudodendrites as the initial manifestation of tyrosinemia type II in monozygotic twins. ( 22588828 )
2012
6
Richner-Hanhart syndrome (tyrosinemia type II): a case report of delayed diagnosis with pseudodendritic corneal lesion. ( 22389994 )
2011
7
Tyrosinemia type II (Richner-Hanhart syndrome): a new mutation in the TAT gene. ( 21145993 )
2011
8
Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations. ( 16574453 )
2006
9
Corneal lesion as the initial manifestation of tyrosinemia type II. ( 16863017 )
2006
10
The narrow substrate specificity of human tyrosine aminotransferase -- the enzyme deficient in tyrosinemia type II. ( 16640556 )
2006
11
[Tyrosinemia type II. Case report]. ( 16050420 )
2005
12
Comparison of the tyrosine aminotransferase cDNA and genomic DNA sequences of normal mink and mink affected with tyrosinemia type II. ( 15817712 )
2005
13
Plantar keratoderma: a manifestation of tyrosinemia type II (Richner-Hanhart syndrome). ( 16270769 )
2005
14
Tyrosinemia type II: nine cases of ocular signs and symptoms. ( 11589874 )
2001
15
Tyrosinemia type II: Report of the first four cases in Saudi Arabia. ( 17344737 )
1998
16
Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type II. ( 9544843 )
1998
17
Tyrosinemia type II: a challenge for ophthalmologists and dermatologists. ( 9144695 )
1997
18
Painful keratoderma and photophobia: hallmarks of tyrosinemia type II. ( 7844676 )
1995
19
Richner-Hanhart syndrome (tyrosinemia type II). Case report and literature review. ( 7648039 )
1995
20
Painful plantar callouses and mental retardation. Tyrosinemia type II. ( 7909424 )
1994
21
Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. ( 1357662 )
1992
22
Early diagnosis of tyrosinemia type II. ( 2712144 )
1989
23
The human tyrosine aminotransferase gene: characterization of restriction fragment length polymorphisms and haplotype analysis in a family with tyrosinemia type II. ( 2456982 )
1988
24
Tyrosinemia type II with incomplete Richner-Hanhart's syndrome. ( 2964425 )
1988
25
Clinical picture and problems of keratoplasty in Richner-Hanhart syndrome (tyrosinemia type II). ( 3054681 )
1988
26
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
27
New forms of hereditary tyrosinemia type II in mink: hepatic tyrosine aminotransferase defect. ( 2876972 )
1986
28
Tyrosinemia type II in two cases previously reported as Richner-Hanhart syndrome. ( 2947825 )
1986
29
Richner-Hanhart syndrome and tyrosinemia type II. ( 6446465 )
1980

Variations for Tyrosinemia, Type Ii

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

75
# Symbol AA change Variation ID SNP ID
1 TAT p.Gly362Val VAR_000560 rs587776511

ClinVar genetic disease variations for Tyrosinemia, Type Ii:

6
(show all 12)
# 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.169C> T (p.Arg57Ter) single nucleotide variant Pathogenic rs118203914 GRCh38 Chromosome 16, 71576247: 71576247
3 TAT NM_000353.2(TAT): c.668C> G (p.Ser223Ter) single nucleotide variant Pathogenic rs118203915 GRCh37 Chromosome 16, 71606127: 71606127
4 TAT NM_000353.2(TAT): c.668C> G (p.Ser223Ter) single nucleotide variant Pathogenic rs118203915 GRCh38 Chromosome 16, 71572224: 71572224
5 TAT NM_000353.2(TAT): c.1249C> T (p.Arg417Ter) single nucleotide variant Pathogenic rs118203916 GRCh37 Chromosome 16, 71602163: 71602163
6 TAT NM_000353.2(TAT): c.1249C> T (p.Arg417Ter) single nucleotide variant Pathogenic rs118203916 GRCh38 Chromosome 16, 71568260: 71568260
7 TAT NM_000353.2(TAT): c.1085G> T (p.Gly362Val) single nucleotide variant Pathogenic rs587776511 GRCh38 Chromosome 16, 71569894: 71569894
8 TAT NM_000353.2(TAT): c.1085G> T (p.Gly362Val) single nucleotide variant Pathogenic rs587776511 GRCh37 Chromosome 16, 71603797: 71603797
9 TAT NM_000353.2(TAT): c.236-5A> G single nucleotide variant Pathogenic rs587776512 GRCh38 Chromosome 16, 71576031: 71576031
10 TAT NM_000353.2(TAT): c.236-5A> G single nucleotide variant Pathogenic rs587776512 GRCh37 Chromosome 16, 71609934: 71609934
11 TAT NM_000353.2(TAT): c.1068G> A (p.Ala356=) single nucleotide variant Likely benign rs202010343 GRCh38 Chromosome 16, 71569911: 71569911
12 TAT NM_000353.2(TAT): c.1068G> A (p.Ala356=) single nucleotide variant Likely benign rs202010343 GRCh37 Chromosome 16, 71603814: 71603814

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
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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