MCID: TYR013
MIFTS: 47

Tyrosinemia, Type Ii

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

Aliases & Classifications for Tyrosinemia, Type Ii

MalaCards integrated aliases for Tyrosinemia, Type Ii:

Name: Tyrosinemia, Type Ii 54 13
Tyrosinemia Type Ii 12 50 24 56 71 52 14
Oculocutaneous Tyrosinemia 12 50 24 56 71
Richner-Hanhart Syndrome 12 24 56 71
Keratosis Palmoplantaris with Corneal Dystrophy 50 24 71
Tyrosine Aminotransferase Deficiency 50 24 71
Tyrosine Transaminase Deficiency 50 24 71
Tyrosinemia Type 2 50 56 29
Tat Deficiency 50 24 71
Tyrosinosis Oculocutaneous Type 50 71
Oregon Type Tyrosinemia 50 24
Tyrosinemia Due to Tyrosine Aminotransferase Deficiency 56
Keratosis Palmoplantaris-Corneal Dystrophy Syndrome 56
Tyrosine Transaminase Deficiency Disease 69
Tyrosinemia Due to Tat Deficiency 56
Richner Hanhart Syndrome 50
Tyrosinemia Oregon Type 71
Tyrosinemia 2 71
Tyrsn2 71

Characteristics:

Orphanet epidemiological data:

56
tyrosinemia type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
tyrosinemia, type ii:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 276600
Disease Ontology 12 DOID:0050725
Orphanet 56 ORPHA28378
UMLS via Orphanet 70 C0268487
ICD10 via Orphanet 34 E70.2
MedGen 40 C0268487
MeSH 42 D020176

Summaries for Tyrosinemia, Type Ii

NIH Rare Diseases : 50 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 hawkinsinuria and dermochondrocorneal dystrophy, and has symptoms including intellectual disability, growth delay and 4-hydroxyphenylpyruvic aciduria. An important gene associated with Tyrosinemia, Type Ii is TAT (Tyrosine Aminotransferase), and among its related pathways/superpathways is Ca, cAMP and Lipid Signaling. The drug Nitisinone has been mentioned in the context of this disorder. Affiliated tissues include skin, eye 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 : 54
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.

Related Diseases for Tyrosinemia, Type Ii

Diseases in the Tyrosinemia family:

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

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

(show all 36)
id Related Disease Score Top Affiliating Genes
1 hawkinsinuria 10.7 FAH TAT
2 dermochondrocorneal dystrophy 10.7 MBTPS2 TP63
3 cone-rod dystrophy 10.7 MBTPS2 TRPV3
4 autism x-linked 4 10.6 MBTPS2 SAT1
5 oligohydramnios 10.6 LCAT TAT
6 liver disease 10.5 KRT12 KRT3 TP63
7 kidney cancer, childhood 10.5 MBTPS2 SAT1
8 chronic cholangitis 10.5 MBTPS2 SAT1
9 breast leiomyoma 10.5 MBTPS2 SAT1 TAT
10 tyrosinemia 10.4
11 communicating hydrocephalus 10.4 MBTPS2 SAT1
12 desbuquois dysplasia 10.4 COL8A2 TGFBI
13 corneal dystrophy, lattice type iiia 10.4 CHST6 TGFBI
14 apparent mineralocorticoid excess 10.3 CHST6 KRT12 TGFBI
15 homocystinuria 10.3 FAH MMD TAT
16 chromosome 3q29 microduplication syndrome 10.2 CHST6 TGFBI
17 hanhart syndrome 10.2
18 carpal tunnel syndrome, familial 10.1 GSN MBTPS2
19 corneal dystrophy, reis-bucklers type 10.1 GSN TGFBI
20 chronic pulmonary heart disease 10.0 KRT12 KRT3 STS TGFBI
21 spinal cord lipoma 10.0 GJB6 KRT3
22 white sponge nevus 1 9.8 CHST6 COL8A2 KRT12 KRT3 TGFBI
23 cowpox 9.8 GSN TACSTD2 TGFBI
24 stromal dystrophy 9.8 CHST6 KRT12 KRT3 TACSTD2 TGFBI
25 corneal dystrophy, avellino type 9.8 TACSTD2 TGFBI
26 hepatitis 9.7
27 constrictive pericarditis 9.7 GJB6 HCCS
28 dysentery 9.7 KRT12 LCAT MBTPS2 SAT1 TGFBI
29 dermatitis 9.5 HCCS MMD
30 epithelial basement membrane dystrophy 9.4 CHST6 GSN KRT12 TACSTD2 TGFBI
31 corneal dystrophy, gelatinous drop-like 9.4 CHST6 GSN KRT12 TACSTD2 TGFBI
32 malignant histiocytic disease 8.9 CHST6 COL8A2 GSN KRT12 KRT3 TACSTD2
33 cerebral artery occlusion 8.0 CHST6 COL8A2 GJB6 GSN KRT12 KRT3
34 corneal dystrophy, epithelial basement membrane 7.9 CHST6 COL8A2 GSN KRT12 KRT3 LCAT
35 acute allergic serous otitis media 7.9 CHST6 COL8A2 GSN KRT12 KRT3 LCAT
36 otosclerosis 4 4.2 CHST6 COL8A2 FAH GJB6 GSN HCCS

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:

54

Lab:
phenylaceticacidemia
soluble tyrosine aminotransferase (tat) deficiency
hydroxyphenylpyruvic aciduria
normal phenylalanine level
normal p-hydroxyphenylpyruvic acid oxidase
more
Neuro:
mental retardation

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

Growth:
growth retardation

Eyes:
herpetiform corneal ulcers


Clinical features from OMIM:

276600

Human phenotypes related to Tyrosinemia, Type Ii:

32 (show all 6)
id Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 growth delay 32 HP:0001510
3 4-hydroxyphenylpyruvic aciduria 32 HP:0003161
4 abnormality of the skin 32 HP:0000951
5 herpetiform corneal ulceration 32 HP:0007812
6 hypertyrosinemia 32 HP:0003231

Drugs & Therapeutics for Tyrosinemia, Type Ii

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


id 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:


id 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 Biomarker for the Early Diagnosis and Monitoring in Tyrosinemia Type 1 Recruiting NCT03284658
10 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:

id Genetic test Affiliating Genes
1 Tyrosinemia Type 2 29
2 Tyrosinemia Type Ii 24 TAT

Anatomical Context for Tyrosinemia, Type Ii

MalaCards organs/tissues related to Tyrosinemia, Type Ii:

39
Skin, Eye, Liver

Publications for Tyrosinemia, Type Ii

Articles related to Tyrosinemia, Type Ii:

(show all 27)
id Title Authors Year
1
Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation. ( 27285949 )
2016
2
In vivo confocal microscopic features of corneal pseudodendritic lesions in tyrosinemia type II. ( 25119963 )
2014
3
Isolated corneal pseudodendrites as the initial manifestation of tyrosinemia type II in monozygotic twins. ( 22588828 )
2012
4
Richner-Hanhart syndrome (tyrosinemia type II): a case report of delayed diagnosis with pseudodendritic corneal lesion. ( 22389994 )
2011
5
Tyrosinemia type II (Richner-Hanhart syndrome): a new mutation in the TAT gene. ( 21145993 )
2011
6
Corneal lesion as the initial manifestation of tyrosinemia type II. ( 16863017 )
2006
7
Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations. ( 16574453 )
2006
8
The narrow substrate specificity of human tyrosine aminotransferase -- the enzyme deficient in tyrosinemia type II. ( 16640556 )
2006
9
Comparison of the tyrosine aminotransferase cDNA and genomic DNA sequences of normal mink and mink affected with tyrosinemia type II. ( 15817712 )
2005
10
Plantar keratoderma: a manifestation of tyrosinemia type II (Richner-Hanhart syndrome). ( 16270769 )
2005
11
[Tyrosinemia type II. Case report]. ( 16050420 )
2005
12
Tyrosinemia type II: nine cases of ocular signs and symptoms. ( 11589874 )
2001
13
Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type II. ( 9544843 )
1998
14
Tyrosinemia type II: Report of the first four cases in Saudi Arabia. ( 17344737 )
1998
15
Tyrosinemia type II: a challenge for ophthalmologists and dermatologists. ( 9144695 )
1997
16
Painful keratoderma and photophobia: hallmarks of tyrosinemia type II. ( 7844676 )
1995
17
Richner-Hanhart syndrome (tyrosinemia type II). Case report and literature review. ( 7648039 )
1995
18
Painful plantar callouses and mental retardation. Tyrosinemia type II. ( 7909424 )
1994
19
Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. ( 1357662 )
1992
20
Early diagnosis of tyrosinemia type II. ( 2712144 )
1989
21
The human tyrosine aminotransferase gene: characterization of restriction fragment length polymorphisms and haplotype analysis in a family with tyrosinemia type II. ( 2456982 )
1988
22
Tyrosinemia type II with incomplete Richner-Hanhart's syndrome. ( 2964425 )
1988
23
Clinical picture and problems of keratoplasty in Richner-Hanhart syndrome (tyrosinemia type II). ( 3054681 )
1988
24
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
25
Tyrosinemia type II in two cases previously reported as Richner-Hanhart syndrome. ( 2947825 )
1986
26
New forms of hereditary tyrosinemia type II in mink: hepatic tyrosine aminotransferase defect. ( 2876972 )
1986
27
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
id Symbol AA change Variation ID SNP ID
1 TAT p.Gly362Val VAR_000560 rs587776511

ClinVar genetic disease variations for Tyrosinemia, Type Ii:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 TAT NM_000353.2(TAT): c.236-5A> G single nucleotide variant Pathogenic rs587776512 GRCh37 Chromosome 16, 71609934: 71609934
2 TAT NM_000353.2(TAT): c.169C> T (p.Arg57Ter) single nucleotide variant Pathogenic rs118203914 GRCh37 Chromosome 16, 71610150: 71610150
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.1249C> T (p.Arg417Ter) single nucleotide variant Pathogenic rs118203916 GRCh37 Chromosome 16, 71602163: 71602163
5 TAT NM_000353.2(TAT): c.1085G> T (p.Gly362Val) single nucleotide variant Pathogenic rs587776511 GRCh38 Chromosome 16, 71569894: 71569894

Expression for Tyrosinemia, Type Ii

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

Pathways for Tyrosinemia, Type Ii

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

id Super pathways Score Top Affiliating Genes
1 10.9 GSN TACSTD2 TRPV3

GO Terms for Tyrosinemia, Type Ii

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

id Name GO ID Score Top Affiliating Genes
1 L-phenylalanine catabolic process GO:0006559 9.26 FAH TAT
2 aromatic amino acid family metabolic process GO:0009072 9.16 FAH TAT
3 tyrosine catabolic process GO:0006572 8.96 FAH TAT
4 steroid metabolic process GO:0008202 8.92 LCAT MBTPS2 STS SULT2B1

Sources for Tyrosinemia, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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42 MeSH
43 MESH via Orphanet
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48 NDF-RT
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59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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70 UMLS via Orphanet
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