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Tyrosinemia type II(TYRSN2)

MedGen UID:
75687
Concept ID:
C0268487
Disease or Syndrome
Synonyms: Keratosis palmoplantaris with corneal dystrophy; Oculocutaneous tyrosinemia; Oregon type tyrosinemia; Richner Hanhart syndrome; TAT deficiency; Tyrosine aminotransferase deficiency; Tyrosine transaminase deficiency; Tyrosinemia type 2; Tyrosinosis oculocutaneous type; TYRSN2
SNOMED CT: Deficiency of tyrosine aminotransferase (124287008); Tyrosinemia type 2 (4887000); Tyrosinemia due to tyrosine aminotransferase deficiency (4887000); Tyrosinemia type II (4887000); Hypertyrosinemia, Richner-Hanhart type (4887000); Tyrosine transaminase deficiency (4887000); Oculocutaneous tyrosinemia (4887000); Richner-Hanhart syndrome (4887000); Hereditary hypertyrosinemia, type II (4887000); Hypertyrosinemia, Oregon type (4887000); Keratosis palmoplantaris with corneal dystrophy (4887000); Persistent hypertyrosinemia (4887000); Richner syndrome (4887000); Tyrosinemia without hepatorenal dysfunction (4887000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): TAT (16q22.2)
 
Monarch Initiative: MONDO:0010160
OMIM®: 276600
Orphanet: ORPHA28378

Definition

Tyrosinemia type II (TYRSN2) 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). [from OMIM]

Additional description

From MedlinePlus Genetics
Tyrosinemia is a genetic disorder characterized by problems breaking down the amino acid tyrosine, which is a building block of most proteins. If the condition is untreated, tyrosine and its byproducts build up in tissues and organs, which can lead to serious health problems.

There are three types of tyrosinemia, distinguished by their symptoms and genetic cause. Tyrosinemia type I is the most severe form of this disorder and usually begins in the first few months of life. Affected infants do not gain weight and grow at the expected rate (failure to thrive) because eating high-protein foods leads to diarrhea and vomiting. Affected infants may also have yellowing of the skin and whites of the eyes (jaundice), a cabbage-like odor, and an increased tendency to bleed (particularly nosebleeds). 

About 1 in 10 of all newborns have temporarily elevated levels of tyrosine (transient tyrosinemia). These cases are not genetic. The most likely causes are vitamin C deficiency or an immature liver due to premature birth.

In addition, tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones (rickets), and an increased risk of liver cancer (hepatocellular carcinoma). Some affected children have repeated neurologic crises that consist of changes in their mental state, reduced sensation in the arms and legs (peripheral neuropathy), abdominal pain, and serious breathing problems (respiratory failure). These crises can last from 1 to 7 days. Without treatment, children with tyrosinemia type I often do not survive past the age of 10. With early diagnosis and treatment, though, affected individuals can live into adulthood.

Tyrosinemia type II often begins in early childhood and affects the eyes, skin, and mental development. Signs and symptoms include eye pain and redness, excessive tearing, abnormal sensitivity to light (photophobia), and thick, painful skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). About half of individuals with tyrosinemia type II have some degree of intellectual disability.

Tyrosinemia type III is the rarest of the three types. The characteristic features of this type include intellectual disabilities, seizures, and periodic loss of balance and coordination (intermittent ataxia). Liver problems do not occur in types II and III.  https://medlineplus.gov/genetics/condition/tyrosinemia

Clinical features

From HPO
4-Hydroxyphenylpyruvic aciduria
MedGen UID:
376416
Concept ID:
C1848678
Finding
Increased relative concentration of 4-hydroxyphenylpyruvic acid in the urine.
Elevated urine N-acetyltyrosine level
MedGen UID:
1053434
Concept ID:
CN377311
Finding
The amount of N-acetyltyrosine in the urine, normalized for urine concentration, is above the upper limit of normal.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypertyrosinemia
MedGen UID:
742296
Concept ID:
C1879362
Disease or Syndrome
An increased concentration of tyrosine in the blood.
Abnormality of the skin
MedGen UID:
11449
Concept ID:
C0037268
Congenital Abnormality
An abnormality of the skin.
Herpetiform corneal ulceration
MedGen UID:
866566
Concept ID:
C4020911
Disease or Syndrome
The presence of one or more dendritic corneal epithelial ulcers characterized by a treelike branching linear pattern with feathery edges and terminal bulbs. Herpetiform corneal ulcers can be identified by fluorescein staining.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTyrosinemia type II

Recent clinical studies

Etiology

Beyzaei Z, Nabavizadeh S, Karimzadeh S, Geramizadeh B
Orphanet J Rare Dis 2022 Dec 5;17(1):424. doi: 10.1186/s13023-022-02579-0. PMID: 36471409Free PMC Article
Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H
Biochem Genet 2018 Apr;56(1-2):7-21. Epub 2017 Nov 1 doi: 10.1007/s10528-017-9825-6. PMID: 29094226
Peña-Quintana L, Scherer G, Curbelo-Estévez ML, Jiménez-Acosta F, Hartmann B, La Roche F, Meavilla-Olivas S, Pérez-Cerdá C, García-Segarra N, Giguère Y, Huppke P, Mitchell GA, Mönch E, Trump D, Vianey-Saban C, Trimble ER, Vitoria-Miñana I, Reyes-Suárez D, Ramírez-Lorenzo T, Tugores A
Clin Genet 2017 Sep;92(3):306-317. Epub 2017 May 18 doi: 10.1111/cge.13003. PMID: 28255985
Gokay S, Kendirci M, Ustkoyuncu PS, Kardas F, Bayram AK, Per H, Poyrazoğlu HG
Pediatr Int 2016 Oct;58(10):1069-1072. Epub 2016 Sep 4 doi: 10.1111/ped.13062. PMID: 27285949
Mehere P, Han Q, Lemkul JA, Vavricka CJ, Robinson H, Bevan DR, Li J
Protein Cell 2010 Nov;1(11):1023-32. Epub 2010 Dec 10 doi: 10.1007/s13238-010-0128-5. PMID: 21153519Free PMC Article

Diagnosis

Thibault LP, Mitchell GA, Parisien B, Hamel P, Blanchard AC
Am J Case Rep 2022 Nov 30;23:e937967. doi: 10.12659/AJCR.937967. PMID: 36447403Free PMC Article
Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H
Biochem Genet 2018 Apr;56(1-2):7-21. Epub 2017 Nov 1 doi: 10.1007/s10528-017-9825-6. PMID: 29094226
Peña-Quintana L, Scherer G, Curbelo-Estévez ML, Jiménez-Acosta F, Hartmann B, La Roche F, Meavilla-Olivas S, Pérez-Cerdá C, García-Segarra N, Giguère Y, Huppke P, Mitchell GA, Mönch E, Trump D, Vianey-Saban C, Trimble ER, Vitoria-Miñana I, Reyes-Suárez D, Ramírez-Lorenzo T, Tugores A
Clin Genet 2017 Sep;92(3):306-317. Epub 2017 May 18 doi: 10.1111/cge.13003. PMID: 28255985
Duchatelet S, Hovnanian A
Orphanet J Rare Dis 2015 Mar 17;10:33. doi: 10.1186/s13023-015-0246-5. PMID: 25886873Free PMC Article
Scott CR
Am J Med Genet C Semin Med Genet 2006 May 15;142C(2):121-6. doi: 10.1002/ajmg.c.30092. PMID: 16602095

Therapy

de Andrade RB, Gemelli T, Rojas DB, Funchal C, Dutra-Filho CS, Wannmacher CM
Metab Brain Dis 2011 Sep;26(3):221-7. Epub 2011 Jul 26 doi: 10.1007/s11011-011-9255-9. PMID: 21789565
Rabinowitz LG, Williams LR, Anderson CE, Mazur A, Kaplan P
J Pediatr 1995 Feb;126(2):266-9. doi: 10.1016/s0022-3476(95)70558-9. PMID: 7844676
Sayar RB, von Domarus D, Schäfer HJ, Beckenkamp G
Ophthalmologica 1988;197(1):1-6. doi: 10.1159/000309909. PMID: 3054681
Lestringant GG
Int J Dermatol 1988 Jan-Feb;27(1):43-4. doi: 10.1111/j.1365-4362.1988.tb02336.x. PMID: 2964425

Prognosis

Thibault LP, Mitchell GA, Parisien B, Hamel P, Blanchard AC
Am J Case Rep 2022 Nov 30;23:e937967. doi: 10.12659/AJCR.937967. PMID: 36447403Free PMC Article
Bouyacoub Y, Zribi H, Azzouz H, Nasrallah F, Abdelaziz RB, Kacem M, Rekaya B, Messaoud O, Romdhane L, Charfeddine C, Bouziri M, Bouziri S, Tebib N, Mokni M, Kaabachi N, Boubaker S, Abdelhak S
Gene 2013 Oct 15;529(1):45-9. Epub 2013 Aug 13 doi: 10.1016/j.gene.2013.07.066. PMID: 23954227

Clinical prediction guides

Beyzaei Z, Nabavizadeh S, Karimzadeh S, Geramizadeh B
Orphanet J Rare Dis 2022 Dec 5;17(1):424. doi: 10.1186/s13023-022-02579-0. PMID: 36471409Free PMC Article
Duchatelet S, Hovnanian A
Orphanet J Rare Dis 2015 Mar 17;10:33. doi: 10.1186/s13023-015-0246-5. PMID: 25886873Free PMC Article
Mehere P, Han Q, Lemkul JA, Vavricka CJ, Robinson H, Bevan DR, Li J
Protein Cell 2010 Nov;1(11):1023-32. Epub 2010 Dec 10 doi: 10.1007/s13238-010-0128-5. PMID: 21153519Free PMC Article
Scott CR
Am J Med Genet C Semin Med Genet 2006 May 15;142C(2):121-6. doi: 10.1002/ajmg.c.30092. PMID: 16602095
Charfeddine C, Monastiri K, Mokni M, Laadjimi A, Kaabachi N, Perin O, Nilges M, Kassar S, Keirallah M, Guediche MN, Kamoun MR, Tebib N, Ben Dridi MF, Boubaker S, Ben Osman A, Abdelhak S
Mol Genet Metab 2006 Jun;88(2):184-91. Epub 2006 Mar 30 doi: 10.1016/j.ymgme.2006.02.006. PMID: 16574453

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Increased Tyrosine, Tyrosinemia, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Tyrosine Elevated, Succinylacetone Normal, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Tyrosine Normal/Elevated, Succinylacetone Elevated, 2022

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