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Hypertyrosinemia

MedGen UID:
742296
Concept ID:
C1879362
Disease or Syndrome
Synonyms: Elevated tyrosine blood level; Increased tyrosine in blood; Tyrosinemia
SNOMED CT: Hypertyrosinemia (56595005); Elevated tyrosine blood level (56595005)
 
HPO: HP:0003231

Definition

An increased concentration of tyrosine in the blood. [from HPO]

Conditions with this feature

Tyrosinosis
MedGen UID:
78683
Concept ID:
C0268484
Disease or Syndrome
Tyrosinemia type II
MedGen UID:
75687
Concept ID:
C0268487
Disease or Syndrome
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).
Tyrosinemia type I
MedGen UID:
75688
Concept ID:
C0268490
Disease or Syndrome
Untreated tyrosinemia type I usually presents either in young infants with severe liver involvement or later in the first year with liver dysfunction and renal tubular dysfunction associated with growth failure and rickets. Untreated children may have repeated, often unrecognized, neurologic crises lasting one to seven days that can include change in mental status, abdominal pain, peripheral neuropathy, and/or respiratory failure requiring mechanical ventilation. Death in the untreated child usually occurs before age ten years, typically from liver failure, neurologic crisis, or hepatocellular carcinoma. Combined treatment with nitisinone and a low-tyrosine diet has resulted in a greater than 90% survival rate, normal growth, improved liver function, prevention of cirrhosis, correction of renal tubular acidosis, and improvement in secondary rickets.
Tyrosinemia type III
MedGen UID:
78694
Concept ID:
C0268623
Disease or Syndrome
Tyrosinemia type III (TYRSN3) is an autosomal recessive disorder caused by a deficiency in the activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) and is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into urine. Patients with this disorder have mild mental retardation and/or convulsions, with the absence of liver damage (summary by Tomoeda et al., 2000).
Neonatal intrahepatic cholestasis due to citrin deficiency
MedGen UID:
340091
Concept ID:
C1853942
Disease or Syndrome
Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2). Often citrin deficiency is characterized by strong preference for protein-rich and/or lipid-rich foods and aversion to carbohydrate-rich foods. NICCD. Children younger than age one year have a history of low birth weight with growth restriction and transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver, and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia, decreased coagulation factors, hemolytic anemia, and/or hypoglycemia. NICCD is generally not severe and symptoms often resolve by age one year with appropriate treatment, although liver transplantation has been required in rare instances. FTTDCD. Beyond age one year, many children with citrin deficiency develop a protein-rich and/or lipid-rich food preference and aversion to carbohydrate-rich foods. Clinical abnormalities may include growth restriction, hypoglycemia, pancreatitis, severe fatigue, anorexia, and impaired quality of life. Laboratory changes are dyslipidemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid (TCA) cycle metabolites. One or more decades later, some individuals with NICCD or FTTDCD develop CTLN2. CTLN2. Presentation is sudden and usually between ages 20 and 50 years. Manifestations are recurrent hyperammonemia with neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive seizures, and coma. Symptoms are often provoked by alcohol and sugar intake, medication, and/or surgery. Affected individuals may or may not have a prior history of NICCD or FTTDCD.
Hawkinsinuria
MedGen UID:
419319
Concept ID:
C2931042
Disease or Syndrome
Hawkinsinuria (HWKS) is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life (Danks et al., 1975; Tomoeda et al., 2000).
Mitochondrial complex III deficiency nuclear type 1
MedGen UID:
762097
Concept ID:
C3541471
Disease or Syndrome
Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001; De Meirleir et al., 2003). Genetic Heterogeneity of Mitochondrial Complex III Deficiency Mitochondrial complex III deficiency can be caused by mutation in several different nuclear-encoded genes. See MC3DN2 (615157), caused by mutation in the TTC19 gene (613814) on chromosome 17p12; MC3DN3 (615158), caused by mutation in the UQCRB gene (191330) on chromosome 8q; MC3DN4 (615159), caused by mutation in the UQCRQ gene (612080) on chromosome 5q31; MC3DN5 (615160), caused by mutation in the UQCRC2 gene (191329) on chromosome 16p12; MC3DN6 (615453), caused by mutation in the CYC1 gene (123980) on chromosome 8q24; MC3DN7 (615824), caused by mutation in the UQCC2 gene (614461) on chromosome 6p21; MC3DN8 (615838), caused by mutation in the LYRM7 gene (615831) on chromosome 5q23; MC3DN9 (616111), caused by mutation in the UQCC3 gene (616097) on chromosome 11q12; and MC3DN10 (618775), caused by mutation in the UQCRFS1 gene (191327) on chromosome 19q12. See also MTYCB (516020) for a discussion of a milder phenotype associated with isolated mitochondrial complex III deficiency and mutations in a mitochondrial-encoded gene.
Mitochondrial DNA depletion syndrome 15 (hepatocerebral type)
MedGen UID:
934657
Concept ID:
C4310690
Disease or Syndrome
Any mitochondrial DNA depletion syndrome in which the cause of the disease is a mutation in the TFAM gene.

Professional guidelines

PubMed

Mitchell GA, Yang H
Adv Exp Med Biol 2017;959:205-213. doi: 10.1007/978-3-319-55780-9_19. PMID: 28755198
Thimm E, Richter-Werkle R, Kamp G, Molke B, Herebian D, Klee D, Mayatepek E, Spiekerkoetter U
J Inherit Metab Dis 2012 Mar;35(2):263-8. Epub 2011 Nov 9 doi: 10.1007/s10545-011-9394-5. PMID: 22069142
Grompe M
Semin Liver Dis 2001 Nov;21(4):563-71. doi: 10.1055/s-2001-19035. PMID: 11745044

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Increased Tyrosine, Tyrosinemia, 2022

American College of Medical Genetics and Genomics, Algorithm, Tyrosine Elevated, Succinylacetone Normal, 2022

Recent clinical studies

Etiology

Kim JS, Kim MG, Ryu JE, Lee YB, Liu QF, Kim KK, Cho SH, Shin SJ, Koo BS, Choi HK
J Ethnopharmacol 2024 Jan 30;319(Pt 3):117359. Epub 2023 Nov 3 doi: 10.1016/j.jep.2023.117359. PMID: 37924999
Imrich R, Zatkova A, Lukacova O, Sedlakova J, Zanova E, Vlcek M, Penesova A, Radikova Z, Havranova A, Ranganath L
Endocr Regul 2023 Jan 1;57(1):61-67. Epub 2023 Mar 26 doi: 10.2478/enr-2023-0008. PMID: 36966367
Mitchell GA, Yang H
Adv Exp Med Biol 2017;959:205-213. doi: 10.1007/978-3-319-55780-9_19. PMID: 28755198
Tessari P, Kiwanuka E, Vettore M, Barazzoni R, Zanetti M, Cecchet D, Orlando R
Am J Physiol Gastrointest Liver Physiol 2008 Sep;295(3):G598-604. Epub 2008 Jul 24 doi: 10.1152/ajpgi.00355.2007. PMID: 18653725
Clow CL, Laberge C, Scriver CR
Can Med Assoc J 1975 Oct 4;113(7):624-6. PMID: 1181017Free PMC Article

Diagnosis

Davison AS, Norman BP
Adv Clin Chem 2023;114:47-81. Epub 2023 Mar 28 doi: 10.1016/bs.acc.2023.02.005. PMID: 37268334
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
Mitchell GA, Yang H
Adv Exp Med Biol 2017;959:205-213. doi: 10.1007/978-3-319-55780-9_19. PMID: 28755198
Grompe M
Semin Liver Dis 2001 Nov;21(4):563-71. doi: 10.1055/s-2001-19035. PMID: 11745044
Russo PA, Mitchell GA, Tanguay RM
Pediatr Dev Pathol 2001 May-Jun;4(3):212-21. doi: 10.1007/s100240010146. PMID: 11370259

Therapy

Imrich R, Zatkova A, Lukacova O, Sedlakova J, Zanova E, Vlcek M, Penesova A, Radikova Z, Havranova A, Ranganath L
Endocr Regul 2023 Jan 1;57(1):61-67. Epub 2023 Mar 26 doi: 10.2478/enr-2023-0008. PMID: 36966367
Mitchell GA, Yang H
Adv Exp Med Biol 2017;959:205-213. doi: 10.1007/978-3-319-55780-9_19. PMID: 28755198
Boels D, Monteil-Ganière C, Turcant A, Bretaudeau M, Harry P
Hum Exp Toxicol 2013 Jul;32(7):778-82. doi: 10.1177/0960327112468908. PMID: 23821594
Thimm E, Herebian D, Assmann B, Klee D, Mayatepek E, Spiekerkoetter U
Mol Genet Metab 2011 Feb;102(2):122-5. Epub 2010 Nov 10 doi: 10.1016/j.ymgme.2010.11.003. PMID: 21112803
Tessari P, Kiwanuka E, Vettore M, Barazzoni R, Zanetti M, Cecchet D, Orlando R
Am J Physiol Gastrointest Liver Physiol 2008 Sep;295(3):G598-604. Epub 2008 Jul 24 doi: 10.1152/ajpgi.00355.2007. PMID: 18653725

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
Russo PA, Mitchell GA, Tanguay RM
Pediatr Dev Pathol 2001 May-Jun;4(3):212-21. doi: 10.1007/s100240010146. PMID: 11370259
Cerone R, Holme E, Schiaffino MC, Caruso U, Maritano L, Romano C
Acta Paediatr 1997 Sep;86(9):1013-5. doi: 10.1111/j.1651-2227.1997.tb15192.x. PMID: 9343288

Clinical prediction guides

Davison AS, Norman BP
Adv Clin Chem 2023;114:47-81. Epub 2023 Mar 28 doi: 10.1016/bs.acc.2023.02.005. PMID: 37268334
Juhl SM
Dan Med J 2017 Jun;64(6) PMID: 28566122
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
Thimm E, Herebian D, Assmann B, Klee D, Mayatepek E, Spiekerkoetter U
Mol Genet Metab 2011 Feb;102(2):122-5. Epub 2010 Nov 10 doi: 10.1016/j.ymgme.2010.11.003. PMID: 21112803
Russo PA, Mitchell GA, Tanguay RM
Pediatr Dev Pathol 2001 May-Jun;4(3):212-21. doi: 10.1007/s100240010146. PMID: 11370259

Supplemental Content

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    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

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