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Tyrosinemias (Tyrosinemia)

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A group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency. Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase. Type II tyrosinemia features mental retardation, painful corneal ulcers, and keratoses of the palms and plantar surfaces and is caused by a deficiency of the enzyme TYROSINE TRANSAMINASE. Type III tyrosinemia features mental retardation and is caused by a deficiency of the enzyme 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE. (Menkes, Textbook of Child Neurology, 5th ed, pp42-3)

Also Known As:

Tyrosinemia; Tyrosinemia, Hereditary; 4-Hydroxyphenol Pyruvic Acid Oxidase Deficiency Disease; Deficiency Disease, 4-Hydroxyphenol Pyruvic Acid Oxidase; Deficiency Disease, Fumarylacetoacetase; Deficiency Disease, Tyrosine Transaminase; Hereditary Tyrosinemia, Type I; Hereditary Tyrosinemia, Type II; Hereditary Tyrosinemia, Type III; Hypertyrosinemia, Type I; Tyrosinemia, Type I; Tyrosinemia, Type II; Tyrosinemia, Type III; Tyrosinemias, Hereditary; 4 Hydroxyphenol Pyruvic Acid Oxidase Deficiency Disease; Deficiency Disease, 4 Hydroxyphenol Pyruvic Acid Oxidase; Deficiency Diseases, Fumarylacetoacetase; Disease, Fumarylacetoacetase Deficiency; Diseases, Fumarylacetoacetase Deficiency; Fumarylacetoacetase Deficiency Diseases; Hereditary Tyrosinemia; Hereditary Tyrosinemias; Hypertyrosinemias, Type I; Type I Hypertyrosinemia; Type I Hypertyrosinemias; Type I Tyrosinemia; Type I Tyrosinemias; Type II Tyrosinemia; Type II Tyrosinemias; Type III Tyrosinemia; Type III Tyrosinemias; Tyrosinemias, Type I; Tyrosinemias, Type II; Tyrosinemias, Type III; 4 Hydroxyphenylpyruvate Dioxygenase Deficiency Disease; Fumarylacetoacetase Deficiency Disease; Tyrosine Transaminase Deficiency Disease

Networked: 446 relevant articles (15 outcomes, 30 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hepatocellular Carcinoma (Hepatoma)
2.	Alkaptonuria
3.	Homocystinuria
4.	Galactosemias (Galactosemia)
5.	Inborn Genetic Diseases (Disease, Hereditary)

Experts

1.	Tanguay, Robert M: 10 articles (12/2015 - 10/2003)
2.	Grompe, Markus: 7 articles (07/2014 - 12/2002)
3.	Ferreira, Gustavo C: 6 articles (04/2014 - 12/2012)
4.	Streck, Emilio L: 6 articles (04/2014 - 12/2012)
5.	Schuck, Patrícia F: 6 articles (04/2014 - 12/2012)
6.	Ferreira, Gabriela K: 6 articles (04/2014 - 12/2012)
7.	Carvalho-Silva, Milena: 6 articles (04/2014 - 12/2012)
8.	Dutra-Filho, Carlos Severo: 5 articles (06/2015 - 10/2008)
9.	Bergeron, Anne: 5 articles (01/2015 - 10/2003)
10.	Orejuela, Diana: 4 articles (12/2015 - 03/2006)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Tyrosinemias:

1.	Tyrosine (L-Tyrosine)FDA Link 10/01/2014 - "Therefore, compounds 3h and 3u could be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation. " 05/01/1995 - "Tyrosinemia was impressed according to elevated plasma tyrosine level and specific metabolites of tyrosine detected by gas chromatography/mass spectrometry (GC/MS) study. " 04/01/1991 - "Analysis of this mutant strain of mouse is expected to provide valuable information on the pathogenesis of human type III tyrosinemia and can also serve as a useful system for studies on tyrosine metabolism." 05/01/1977 - "Metabolic studies on two patients with nonhepatic tyrosinemia using deuterated tyrosine loads." 02/01/2015 - "A definitive diagnosis of tyrosinemia type I is difficult to obtain based only on blood tyrosine level. "
2.	succinylacetoneIBA 06/01/2011 - "In 2 years, the New York newborn screening program has analyzed approximately 500,000 samples for succinylacetone (SUAC), the biomarker for Tyrosinemia, type I. There have been five screen-positive results. " 01/01/2016 - "Succinylacetone (SA) is used for the diagnosis and monitoring of patients with tyrosinemia type I (Tyr I). " 09/01/2014 - "Succinylacetone as primary marker to detect tyrosinemia type I in newborns and its measurement by newborn screening programs." 08/16/2012 - "Both hematocrit and blood volume have effect on analysis of succinylacetone in dried blood spots, the effect of hematocrit is more significant, due to hematocrit level of majority Type I tyrosinemia patients is low, diagnoses may be missed by using dried blood spots to analysis." 02/01/2012 - "A total of 190 patients suspected of having tyrosinemia, were tested by tandem mass spectrometry for measurement of the level of succinylacetone in the blood, and detected by gas chromatography-mass spectrometry for measurement of the level of succinylacetone and organic acid in the urine. "
3.	nitisinone (Orfadin)FDA Link 05/01/2015 - "To estimate the direct medical costs of health care services related to the treatment of tyrosinemia type I, taking into consideration the real-life efficacy of nitisinone. " 03/15/2010 - "2-(2-Nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) is a relatively new drug which is used to prevent the accumulation of toxic metabolites in patients with hereditary tyrosinemia type I. In the present study, we have developed a new, simple, fast, and cost-effective capillary electrophoresis method for the quantitative monitoring of this drug in serum samples. " 07/09/1999 - "The chemical substance 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) is in clinical use for the treatment of hereditary tyrosinemia type 1. In the present study, the plasma concentration of NTBC was determined by a coupled column liquid chromatographic method. " 12/01/2015 - "Pharmacological and clinical profile of nitisinone (Orfadin(®) Capsules): a therapeutic agent for hereditary tyrosinemia type 1." 05/01/2015 - "Cost-Consequence Analysis of Nitisinone for Treatment of Tyrosinemia Type I."
4.	Homogentisic AcidIBA 08/01/1990 - "Homogentisic acid (HGA) (50 mg/kg) was given orally to 22 obligate heterozygotes for hereditary tyrosinemia type 1 (HT) and to 11 controls. " 08/01/1990 - "Oral loading of homogentisic acid in controls and in obligate heterozygotes for hereditary tyrosinemia type I." 10/01/1975 - "But, they had an excessive amount of blood tyrosine (Tyr), and concurrently excreted massive homogentisic acid (HGA) in urine just as in human tyrosinemia alkaptonuria. " 01/01/2012 - ", there is no proven treatment for alkaptonuria but emergence of orphan drug legislation internationally has promoted the licensing of nitisinone (Orfadin™) for an equally rare disorder of tyrosine metabolism - hereditary tyrosinaemia type 1. Nitisinone, a triketone competitive inhibitor of a proximal step leading to the formation of homogentisic acid, has potent therapeutic effects in hereditary tyrosinemia and rapidly ameliorates the primary biochemical abnormality in patients with alkaptonuria.Here" 08/15/2005 - "In this bacterium, deletion of the homogentisate gene cluster (hmgRABC) confers upon this mutant huge biotechnological possibilities since it can be used: (i) as a target for testing new specific herbicides (p-hydroxy-phenylpyruvate dioxygenase inhibitors); (ii) to identify new therapeutic drugs-effective in the treatment of alkaptonuria and other related tyrosinemia - and (iii) as a source of homogentisic acid in a plant-bacterium association."
5.	DNA (Deoxyribonucleic Acid)IBA 08/11/1994 - "This study identified the most prevalent mutation causing hereditary tyrosinemia in French Canada; it also showed the feasibility of DNA-based testing for carriers in the population at risk." 09/07/2015 - "By coupling target DNA-induced reconfiguration of the dsDNA probes with enzyme-assisted target recycling amplification, we describe the development of a signal-on electrochemical sensing approach for sensitive detection of hereditary tyrosinemia type I gene. " 01/01/2014 - "In conclusion, the present work demonstrated that DNA damage can be encountered in brain from animal models of hypertyrosinemia, DNA alterations may represent a further means to explain neurological dysfunction in this inherited metabolic disorder and to reinforce the role of oxidative stress in the pathophysiology of tyrosinemia type II." 10/08/2010 - "Hereditary tyrosinemia type 1 metabolites impair DNA excision repair pathways." 12/01/2002 - "In vivo correction of murine tyrosinemia type I by DNA-mediated transposition."
6.	alpha-Fetoproteins (AFP)IBA 02/01/1994 - "Serum levels of oncofetal markers CA 125, CA 19-9, and alpha-fetoprotein in children with hereditary tyrosinemia type I." 09/01/1990 - "[Alpha fetoprotein and type I tyrosinemia]." 05/01/1973 - "II. Comparative tissue levels of alpha-fetoprotein in 2 cases of hereditary tyrosinemia. " 05/01/1973 - "I. Clinical value of alpha-fetoprotein in hereditary tyrosinemia]." 06/01/2006 - "The age at diagnosis of the HCC or HB ranged from 9.5 to 17 yr and male:female ratio was 1:4. During regular clinic visits for tyrosinemia, elevated alpha-fetoprotein (AFP) was detected in all patients. "
7.	Amino Acids FDA Link 01/01/2008 - "We studied spots from 13,000 neonates born in Tuscany (January-May 2007) and ten spots from six patients with tyrosinemia type I. The traditional screening method was modified by adding dioxooctanoid acid (or 13C2-succinylacetone) as an internal standard to the methanolic solution of deuterated acylcarnitines and amino acids. " 01/01/1999 - "Using a low expense thin-layer chromatography (TLC) for amino acids we detected a high frequency of transient tyrosinemia with secondary hyperphenylalaninemia in some newborns. " 07/10/2007 - "Experiments to identify and compare amino acids and related metabolites in normal human urine and serum samples as well as in urine from patients with the inborn errors of metabolism tyrosinemia type II, argininosuccinic aciduria, homocystinuria, and phenylketonuria demonstrate the method. " 12/01/1996 - "Phenylketonuria, tyrosinemia, cystinuria, ornithinemia, argininosuccinic aciduria, maple syrup urine disease (MSUD), alkaptonuria, lysinuria and other genetic pathologies were in fact unambiguously and rapidly diagnosed by means of the identification in the biological fluids of the relevant accumulating amino acids and/or of their metabolites. " 05/12/2011 - "Improved tandem mass spectrometry (MS/MS) derivatized method for the detection of tyrosinemia type I, amino acids and acylcarnitine disorders using a single extraction process."
8.	HerbicidesIBA 01/01/2009 - "One of these herbicides, 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), is so selective and efficient that it can be applied as a medicine in a hereditary metabolic disease - tyrosinemia type I. In this paper the available information concerning the molecular mechanism of HPPD inhibition by NTBC, originating from experimental investigations as well as theoretical modeling, has been collected. " 12/09/2005 - "While several di- and tri-ketone alkaloids are known as inhibitors of HPPD and used commercially as herbicides, one such inhibitor, [2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), has also been used therapeutically to treat type I tyrosinemia and alkaptonuria in humans. " 08/15/2005 - "In this bacterium, deletion of the homogentisate gene cluster (hmgRABC) confers upon this mutant huge biotechnological possibilities since it can be used: (i) as a target for testing new specific herbicides (p-hydroxy-phenylpyruvate dioxygenase inhibitors); (ii) to identify new therapeutic drugs-effective in the treatment of alkaptonuria and other related tyrosinemia - and (iii) as a source of homogentisic acid in a plant-bacterium association."
9.	Coenzyme A (CoA)IBA 05/01/2008 - "Were obtained seven positive results, one for each disorder: homocystinuria, hyperphenylalaninemia, citrulinemia, transient tyrosinemia, 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl CoA deficiency, and classic galactosemia. " 04/01/2003 - "The disease profile was consisted of methylmalonic acidemias (6), alpha-keto-glutaric aciduria (5), tyrosinemia type I (4), dicarboxylic aciduria (4), multiple carboxylase deficiency (3), phenylketonuria (3), lactic acidemia (3), propionic acidemia (2), ornithine transcarbamoylase deficiency (1), ethylmalonic-adipic aciduria (1), glutaric aciduria type II (1) and 3-methylcrotyl CoA carboxylase deficiency (1). " 08/05/2008 - "319 of the 4981 children (6.4%) were diagnosed as with 24 kinds of diseases: 155 of the 319 cases (48.6%) with 8 kinds of amino acid diseases (97 with hyperphenylalaninemia, 14 with maple syrup urine disease 13 with ornithine transcarbamylase deficiency, 13 with citrullinemia type II, 10 with tyrosinemia type I, 5 with citrullinemia type I, 2 with homocystinuria, and 1 with arginasemia); 150 of the 319 cases (47.0%) were diagnosed as with 10 kinds of organic acidemias (81 with methylmalonic acidemia, 17 with propionic acidemia, 17 with multiple CoA carboxylase deficiency, 11 with glutaric acidemia type II, 8 with isovaleric acidemia, 6 with beta-keto thiolase deficiency, 5 with 3-methylcrotonyl-CoA carboxylase deficiency, and 3 with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency); 14 cases (4.4%) were diagnosed as with 6 kinds of fatty acid disorders (5 with medium chain acyl-CoA dehydrogenase deficiency, 3 with very long chain acyl CoA dehydrogenase deficiency, 2 with short chain acyl-CoA dehydrogenase deficiency, 2 with multiple acyl-CoA dehydrogenase deficiency, 1 with carnitine palmitoyl transferase type II, and 1 with carnitine palmitoyl transferase type I). "
10.	First StepIBA 03/28/1995 - "The possibility to express FAH stably in deficient patients represents a first step towards future gene therapy for type I hereditary tyrosinemia and may help to decipher the pathogenesis of the disease at the molecular level."

Therapies and Procedures

1.	Liver Transplantation 11/01/2000 - "NTBC treatment has greatly improved the survival of patients with acute tyrosinemia and has reduced the need for liver transplantation during early childhood. " 03/01/1987 - "Contribution of extrahepatic tissues to biochemical abnormalities in hereditary tyrosinemia type I: study of three patients after liver transplantation." 12/01/2013 - "Clinical and para clinical findings in the children with tyrosinemia referring for liver transplantation." 10/01/2011 - "Long-term outcome of living donor liver transplantation in a Thai boy with hereditary tyrosinemia type I: a case report." 06/01/2011 - "Liver transplantation for hereditary tyrosinemia type I: analysis of the UNOS database."
2.	Transplants (Transplant) 08/01/2015 - "Between September 2006, and June 2011, thirty-six patients with hereditary tyrosinemia type 1 received a liver transplant from a deceased (whole or split) or a living-related donor. " 07/01/1991 - "Nevertheless, all five suffered significant and unexpected complications of tyrosinemia prior to the time of liver transplant. " 07/01/1991 - "In an effort to determine whether any factors in these patients would aid in predicting optimal timing of the transplant procedure, we evaluated several clinical, biochemical, and radiographic parameters in five successive patients undergoing liver transplant for tyrosinemia type I at the University of Minnesota. " 10/01/1978 - "Liver transplant appears to be an effective method of enzyme replacement in tyrosinemia and should be considered for prevention of hepatoma." 08/01/2015 - "The prevalence of cell dysplasia and hepatocellular carcinoma in children with hereditary tyrosinemia type 1 in our study is not as high as that reported previously, so it appears that patients older than 2 years of age require a liver transplant."
3.	Transplantation (Transplant Recipients) 02/01/1992 - "To characterize better the temporal course of the improvement in renal excretory activity following hepatic replacement, renal tubular function and metabolite excretion were studied in a 4-year-old girl with hereditary tyrosinemia during the immediate post-transplantation course. " 01/01/2005 - "While this is certainly true for murine tyrosinemia models, we have used a Cre-lox system to demonstrate that fusion is not a requirement for the generation of BM-derived epithelial cells and is likely not responsible for the BM-derived epithelial cells generated after standard BM transplantation. " 02/01/1992 - "This is the third tyrosinemia patient reported to achieve complete resolution of urinary abnormalities following transplantation, and the only patient in whom renal tubular function was formally assessed within the first postoperative week." 12/01/1993 - "For this reason, and while most patients with tyrosinemia will eventually require liver transplantation, our results do not support systematic early transplantation before the age of two years." 01/01/1993 - "For this reason, and while most patients with tyrosinemia will eventually require liver transplantation, our results do not support systematic early transplantation."
4.	Protein-Restricted Diet (Diet, Protein Restricted) 03/01/1975 - "Severe tyrosyluria and mild tyrosinemia cleared on a low-protein diet which also corrected the acidosis. " 05/01/1998 - "Rats fed L-tyrosine at 5% w/w in a low-protein diet rapidly develop lesions to the cornea of the eye, which are associated with a marked tyrosinemia, increased hepatic tyrosine aminotransferase activity, and about a 50% reduction in the activity of hepatic HPPD. " 05/01/1998 - "The effect of a low-protein diet and dietary supplementation of threonine on tyrosine and 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione-induced corneal lesions, the extent of tyrosinemia, and the activity of enzymes involved in tyrosine catabolism in the rat."
5.	Aftercare (After-Treatment) 05/01/1998 - "The protection afforded by threonine inclusion in the diet was not due to any amelioration in the extent of inhibition of hepatic HPPD activity or reduction in the extent of the tyrosinemia as measured 8 days after treatment. " 05/15/2010 - "We were able to show variations in DNA methylation after treatment of cultured cells with 5-azacytidine and succinylacetone, an accumulating metabolite in human tyrosinemia type I."