tyrosinemias

Summary

Summary: 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 INTELLECTUAL DISABILITY, 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 INTELLECTUAL DISABILITY and is caused by a deficiency of the enzyme 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE. (Menkes, Textbook of Child Neurology, 5th ed, pp42-3)

Top Publications

  1. Wilson C, Van Wyk K, Leonard J, Clayton P. Phenylalanine supplementation improves the phenylalanine profile in tyrosinaemia. J Inherit Metab Dis. 2000;23:677-83 pubmed
    ..Further studies are needed to investigate the longer-term clinical and biochemical consequences of phenylalanine supplementation...
  2. Schlump J, Mayatepek E, Spiekerkoetter U. Significant increase of succinylacetone within the first 12 h of life in hereditary tyrosinemia type 1. Eur J Pediatr. 2010;169:569-72 pubmed publisher
    ..In most countries, hereditary tyrosinemia type 1 is not included in routine newborn screening...
  3. Daly A, Gokmen Ozel H, MacDonald A, Preece M, Davies P, Chakrapani A, et al. Diurnal variation of phenylalanine concentrations in tyrosinaemia type 1: should we be concerned?. J Hum Nutr Diet. 2012;25:111-6 pubmed publisher
    ..Low plasma phenylalanine <30 ?m may be associated with poor growth and cognitive delay. The present study aimed to document diurnal variation of tyrosine and phenylalanine plasma concentrations and growth in children with HT1...
  4. Couce M, Dalmau J, Del Toro M, Pintos Morell G, Aldámiz Echevarría L. Tyrosinemia type 1 in Spain: mutational analysis, treatment and long-term outcome. Pediatr Int. 2011;53:985-9 pubmed publisher
    ..The aim of the present study was to review the efficacy of long-term treatment of HT1 with nitisinone, expand knowledge about the clinical spectrum of the disease and assess a possible genotype-phenotype correlation...
  5. PAULK N, Wursthorn K, Wang Z, Finegold M, Kay M, Grompe M. Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo. Hepatology. 2010;51:1200-8 pubmed publisher
    ..In this model, repaired hepatocytes have a selective growth advantage and are thus able to proliferate to efficiently repopulate mutant livers and cure the underlying metabolic disease...
  6. Thimm E, Herebian D, Assmann B, Klee D, Mayatepek E, Spiekerkoetter U. Increase of CSF tyrosine and impaired serotonin turnover in tyrosinemia type I. Mol Genet Metab. 2011;102:122-5 pubmed publisher
  7. Schulze A, Frommhold D, Hoffmann G, Mayatepek E. Spectrophotometric microassay for delta-aminolevulinate dehydratase in dried-blood spots as confirmation for hereditary tyrosinemia type I. Clin Chem. 2001;47:1424-9 pubmed
    ..We developed a semiquantitative assay based on inhibition of delta-aminolevulinate dehydratase (ALA-D) by succinylacetone...
  8. Crone J, Möslinger D, Bodamer O, Schima W, Huber W, Holme E, et al. Reversibility of cirrhotic regenerative liver nodules upon NTBC treatment in a child with tyrosinaemia type I. Acta Paediatr. 2003;92:625-8 pubmed
    ..Augmentation of NTBC dosage resulted in a decrease in serum alpha-fetoprotein levels and in significant regression of liver nodules on MRI...
  9. Gissen P, Preece M, Willshaw H, McKiernan P. Ophthalmic follow-up of patients with tyrosinaemia type I on NTBC. J Inherit Metab Dis. 2003;26:13-6 pubmed
    ..Despite high plasma tyrosine concentrations in some patients, they did not experience symptoms or signs of ocular toxicity...

More Information

Publications88

  1. Koelink C, van Hasselt P, van der Ploeg A, van den Heuvel Eibrink M, Wijburg F, Bijleveld C, et al. Tyrosinemia type I treated by NTBC: how does AFP predict liver cancer?. Mol Genet Metab. 2006;89:310-5 pubmed
    ..Still, some patients with NTBC treatment develop liver cancer. A rise of alpha-fetoprotein (AFP) is an indicator of liver cancer...
  2. Weigel J, Janzen N, Pfaffle R, Thiery J, Kiess W, Ceglarek U. Tandem mass spectrometric determination of succinylacetone in dried blood spots enables presymptomatic detection in a case of hepatorenal tyrosinaemia. J Inherit Metab Dis. 2007;30:610 pubmed
    ..This indicates that identification of all newborns with hepatorenal tyrosinaemia is only possible by determination of succinylacetone as part of the newborn screening process...
  3. Masurel Paulet A, Poggi Bach J, Rolland M, Bernard O, Guffon N, Dobbelaere D, et al. NTBC treatment in tyrosinaemia type I: long-term outcome in French patients. J Inherit Metab Dis. 2008;31:81-7 pubmed publisher
    ..A more restricted diet could be necessary to prevent the neurological impact of the disease...
  4. Couce M, Aldámiz Echevarría L, Baldellou A, Blasco J, Bueno M, Dalmau J, et al. [Recommendations and management of type I hereditary or hepatorenal tyrosinemia]. An Pediatr (Barc). 2010;73:279.e1-4 pubmed publisher
    ..It is therefore important that the pediatrician has a clinical practice guideline with recommendations for diagnosis and treatment of this disease that leads to the appropriate intervention...
  5. Schiff M, Broue P, Chabrol B, De Laet C, Habes D, Mention K, et al. Heterogeneity of follow-up procedures in French and Belgian patients with treated hereditary tyrosinemia type 1: results of a questionnaire and proposed guidelines. J Inherit Metab Dis. 2012;35:823-9 pubmed publisher
    ..In an attempt to improve long-term management and outcome of patients with HT-1, we proposed follow-up recommendations...
  6. Larochelle J, Alvarez F, Bussières J, Chevalier I, Dallaire L, Dubois J, et al. Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec. Mol Genet Metab. 2012;107:49-54 pubmed publisher
    ..Nitisinone (NTBC, Orfadin ®) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone and has been offered to HT1 patients in Québec since 1994...
  7. Arora N, Stumper O, Wright J, Kelly D, McKiernan P. Cardiomyopathy in tyrosinaemia type I is common but usually benign. J Inherit Metab Dis. 2006;29:54-7 pubmed
    ..Tyrosinaemia type I (TTI) is an inherited multisystemic disorder of tyrosine metabolism. In addition to hepatic and renal involvement, cardiomyopathy is an important clinical manifestation...
  8. Lock E, Gaskin P, Ellis M, Provan W, Smith L. Tyrosinemia produced by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) in experimental animals and its relationship to corneal injury. Toxicol Appl Pharmacol. 2006;215:9-16 pubmed
  9. la Marca G, Malvagia S, Materazzi S, Della Bona M, Boenzi S, Martinelli D, et al. LC-MS/MS method for simultaneous determination on a dried blood spot of multiple analytes relevant for treatment monitoring in patients with tyrosinemia type I. Anal Chem. 2012;84:1184-8 pubmed publisher
  10. Schlump J, Perot C, Ketteler K, Schiff M, Mayatepek E, Wendel U, et al. Severe neurological crisis in a patient with hereditary tyrosinaemia type I after interruption of NTBC treatment. J Inherit Metab Dis. 2008;31 Suppl 2:S223-5 pubmed publisher
    ..After re-introduction of NTBC the patient slowly regained normal neurological functions and recovered completely...
  11. Thimm E, Richter Werkle R, Kamp G, Molke B, Herebian D, Klee D, et al. Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC. J Inherit Metab Dis. 2012;35:263-8 pubmed publisher
    ..However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations...
  12. Baumann U, Duhme V, Auth M, McKiernan P, Holme E. Lectin-reactive alpha-fetoprotein in patients with tyrosinemia type I and hepatocellular carcinoma. J Pediatr Gastroenterol Nutr. 2006;43:77-82 pubmed
    ..Lectin-affinity electrophoresis may have a role in discriminating benign liver disease from HCC in HT1. We suggest the further evaluation of L3-AFP in HT1...
  13. Schlune A, Thimm E, Herebian D, Spiekerkoetter U. Single dose NTBC-treatment of hereditary tyrosinemia type I. J Inherit Metab Dis. 2012;35:831-6 pubmed publisher
    ..In fact, single dose treatment may increase patients' compliance with the drug treatment and improve metabolic control...
  14. Hall M, Wilks M, Provan W, Eksborg S, Lumholtz B. Pharmacokinetics and pharmacodynamics of NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione) and mesotrione, inhibitors of 4-hydroxyphenyl pyruvate dioxygenase (HPPD) following a single dose to healthy male volunteers. Br J Clin Pharmacol. 2001;52:169-77 pubmed
    ..Additionally, the urinary excretion of unchanged mesotrione was measured to assess the importance of this route of clearance and to help develop a strategy for monitoring occupational exposure...
  15. Bergeron A, D Astous M, Timm D, Tanguay R. Structural and functional analysis of missense mutations in fumarylacetoacetate hydrolase, the gene deficient in hereditary tyrosinemia type 1. J Biol Chem. 2001;276:15225-31 pubmed
  16. Kim S, Kupke K, Ierardi Curto L, Holme E, Greter J, Tanguay R, et al. Hepatocellular carcinoma despite long-term survival in chronic tyrosinaemia I. J Inherit Metab Dis. 2000;23:791-804 pubmed
    ..This case demonstrates the high risk of liver cancer in tyrosinaemia I even in a seemingly favourable biological environment...
  17. Al Dirbashi O, Rashed M, Jacob M, Al Ahaideb L, Al Amoudi M, Rahbeeni Z, et al. Improved method to determine succinylacetone in dried blood spots for diagnosis of tyrosinemia type 1 using UPLC-MS/MS. Biomed Chromatogr. 2008;22:1181-5 pubmed publisher
    ..63 micromol/L (n = 151). In dried blood spots from patients with established tyrosinemia type 1 (n = 11), concentration of succinylacetone was 6.4-30.8 micromol/L...
  18. Santra S, Baumann U. Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008;9:1229-36 pubmed publisher
    ..Since 1992, nitisinone - a compound developed from work on triketone herbicides - has become an effective pharmacological treatment by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase...
  19. Baumann U, Preece M, Green A, Kelly D, McKiernan P. Hyperinsulinism in tyrosinaemia type I. J Inherit Metab Dis. 2005;28:131-5 pubmed
    ..In patients with persistent hypoglycaemia, C-peptide should always be measured. Treatment with diazoxide and chlorthiazide is highly effective, appears to be safe, and does not need to be continued lifelong...
  20. Held P, Olivares E, Aguilar C, Finegold M, Calos M, Grompe M. In vivo correction of murine hereditary tyrosinemia type I by phiC31 integrase-mediated gene delivery. Mol Ther. 2005;11:399-408 pubmed
    ..The stability of transgene expression, relatively high integration frequency, and significant site specificity that characterize the phiC31 integration system suggest that it may have utility in many gene therapy settings...
  21. Montini E, Held P, Noll M, Morcinek N, Al Dhalimy M, Finegold M, et al. In vivo correction of murine tyrosinemia type I by DNA-mediated transposition. Mol Ther. 2002;6:759-69 pubmed
    ..Molecular analysis indicated that high-efficiency DNA-mediated transposition into the mouse genome was strictly dependent on the expression of wild-type transposase...
  22. Morrissey M, Sunny S, Fahim A, Lubowski C, Caggana M. Newborn screening for Tyr-I: two years' experience of the New York State program. Mol Genet Metab. 2011;103:191-2 pubmed publisher
    ..Two of these results were considered borderline, and a repeat specimen was requested. In three cases, an immediate referral was made to a specialty care center. Two of those three cases were confirmed for Tyr-I...
  23. El Karaksy H, Rashed M, El Sayed R, El Raziky M, El Koofy N, El Hawary M, et al. Clinical practice. NTBC therapy for tyrosinemia type 1: how much is enough?. Eur J Pediatr. 2010;169:689-93 pubmed publisher
    ..Succinylacetone was undetectable in urine on these doses...
  24. Herzog D, Martin S, Turpin S, Alvarez F. Normal glomerular filtration rate in long-term follow-up of children after orthotopic liver transplantation. Transplantation. 2006;81:672-7 pubmed
    ..Impairment of kidney function was associated with congenital kidney disease, toxic kidney injury, and portal hypertension. ..
  25. Cerone R, Fantasia A, Castellano E, Moresco L, Schiaffino M, Gatti R. Pregnancy and tyrosinaemia type II. J Inherit Metab Dis. 2002;25:317-8 pubmed
    ..During pregnancies, plasma tyrosine was raised. The outcomes of both offspring show that maternal tyrosinaemia may have an adverse effect on the developing fetus. ..
  26. Wästfelt M, Fadeel B, Henter J. A journey of hope: lessons learned from studies on rare diseases and orphan drugs. J Intern Med. 2006;260:1-10 pubmed
    ..These lessons, along with the crucial importance of cooperation between academic institutions, pharmaceutical companies, patient advocacy groups and society in the elucidation of rare diseases, are highlighted in the present review. ..
  27. Szczeciński P, Lamparska D, Gryff Keller A, Gradowska W. Identification of 2-[2-nitro-4-(trifluoromethyl)benzoyl]- cyclohexane-1,3-dione metabolites in urine of patients suffering from tyrosinemia type I with the use of 1H and 19F NMR spectroscopy. Acta Biochim Pol. 2008;55:749-52 pubmed
  28. Perlmutter D, Azevedo R, Kelly D, Shepherd R, Tazawa Y. Metabolic liver disease: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2002;35 Suppl 2:S180-6 pubmed
  29. Sander J, Janzen N, Terhardt M, Sander S, Gokcay G, Demirkol M, et al. Monitoring tyrosinaemia type I: Blood spot test for nitisinone (NTBC). Clin Chim Acta. 2011;412:134-8 pubmed publisher
    ..56 ± 0.13. As demonstrated in patients with tyrosinaemia type I quantification of NTBC by UPLC-MS/MS in blood spots is feasible and gives valuable information for monitoring NTBC treatment. ..
  30. Ozcay F, Canan O, Bilezikci B, Torgay A, Karakayali H, Haberal M. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma. Clin Transplant. 2006;20:776-82 pubmed
    ..Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates. ..
  31. Huang Y, Li X, Luo X, Wei H, Song Y. [One case of hereditary tyrosinemia type I]. Zhonghua Er Ke Za Zhi. 2003;41:309 pubmed
  32. McKiernan P. Nitisinone in the treatment of hereditary tyrosinaemia type 1. Drugs. 2006;66:743-50 pubmed
    ..Nitisinone is indicated for all children with HT-1, and liver transplantation is only indicated where nitisinone fails, or where the development of HCC is likely or suspected. ..
  33. Evans A. An infant with otitis media and abdominal distension. Clin Pediatr (Phila). 2002;41:537-8; discussion 538-41 pubmed
  34. Yokoyama Y, Yamasaki K, Sato H. Simultaneous determination of urinary creatinine and UV-absorbing amino acids using a novel low-capacity cation-exchange chromatography for the screening of inborn errors of metabolism. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;816:333-8 pubmed
    ..9994 and 0.9999. The method could provide the creatinine ratios for the analytes, and was applicable to the screening and/or chemical diagnosis of several inherited disorders of amino-acid metabolism such as phenylketonuria (PKU). ..
  35. Grompe M. The pathophysiology and treatment of hereditary tyrosinemia type 1. Semin Liver Dis. 2001;21:563-71 pubmed
  36. Royer L, Knudsen F, de Oliveira M, Tavares M, Bechara E. Succinylacetone oxidation by oxygen/peroxynitrite: a possible source of reactive intermediates in hereditary tyrosinemia type I. Chem Res Toxicol. 2004;17:598-604 pubmed
    ..The results obtained may help shed light on the role of both SA and oxidative stress in the pathogenesis of HT1. ..
  37. Cakir M, Mutlu M, Aydin Mungan S, Cansu A, Aslan Y, Erduran E. Neonatal hemochromatosis: a case report with unique presentation. Turk J Pediatr. 2011;53:455-9 pubmed
    ..Early diagnosis and aggressive treatment are important as in galactosemia or tyrosinemia for the outcome. Thus, NH may be listed as a treatable cause of ALF in neonates. ..
  38. Bergeron A, Jorquera R, Tanguay R. [Hereditary tyrosinemia: an endoplasmic reticulum stress disorder?]. Med Sci (Paris). 2003;19:976-80 pubmed
    ..These effects may underlie the tumorigenic phenomenon observed in HT1. Fumarylacetoacetate in addition to causing disturbances in Ca2+ homeostasis, may induce endoplasmic reticulum stress. ..
  39. Shinka T, Kuhara T. Quantification of urinary 5-aminolevulinic acid by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;806:19-23 pubmed
    ..4 mmol/mol creatinine and 0.54+/- 0.49 mmol/mol creatinine (n = 7), respectively, were detected. Less than 0.2 ml urine was sufficient for the determination of 5-aminolevulinic acid in healthy subjects. ..
  40. Fisher A, Page K, Lithgow G, Nash L. The Caenorhabditis elegans K10C2.4 gene encodes a member of the fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of type I tyrosinemia. J Biol Chem. 2008;283:9127-35 pubmed publisher
    ..We also use our model to identify genes that suppress the damage produced by K10C2.4 RNAi in a pilot genetic screen. Our results establish worms as a model for the study of type I tyrosinemia. ..
  41. Benatiya A, Bouayed M, Touiza E, Daoudi K, Bhalil S, Elmesbahi I, et al. [Tyrosinemia type II. Case report]. Bull Soc Belge Ophtalmol. 2005;:57-61 pubmed
    ..This disease must be suspected in all cases of dentritic keratitis not reacting on the antiviral treatment, and more especially if it is associated with cutaneous lesions such as palmo-plantar keratosis. ..
  42. Mak C, Lam C, Chim S, Siu T, Ng K, Tam S. Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong. Clin Biochem. 2013;46:155-9 pubmed publisher
    ..Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong. ..
  43. Ferreira G, Carvalho Silva M, Gonçalves C, Vieira J, Scaini G, Ghedim F, et al. L-tyrosine administration increases acetylcholinesterase activity in rats. Neurochem Int. 2012;61:1370-4 pubmed publisher
  44. Dragani T. Risk of HCC: genetic heterogeneity and complex genetics. J Hepatol. 2010;52:252-7 pubmed publisher
  45. Jitraruch S, Treepongkaruna S, Teeraratkul S, Wattanasirichaigoon D, Leelaudomlipi S, Sornmayura P, et al. Long-term outcome of living donor liver transplantation in a Thai boy with hereditary tyrosinemia type I: a case report. J Med Assoc Thai. 2011;94:1276-80 pubmed
    ..Liver transplantation is a promising treatment for patients with HT-1 when NTBC is unavailable, resulting in a good long-term outcome. ..
  46. Van Dyk E, Pretorius P. Impaired DNA repair and genomic stability in hereditary tyrosinemia type 1. Gene. 2012;495:56-61 pubmed publisher
    ..Results from microsatellite instability analyses show allelic imbalance on chromosome 7 of the fah(-/-) mouse genome, and instability of the D2S123, D5S346 and (possibly) D17S250 microsatellite markers, in HT1 patient lymphocytes. ..
  47. Osorio Orozco J, Pourfarzam M. [Diagnostic error of mental retardation of neurometabolic origin confirmed by mass sequential spectrometry]. Rev Neurol. 2000;30:728-30 pubmed
    ..Is necessary to improve the diagnosis methods used in some countries in order to avoid mistakes that can change the life-style of the wrongly diagnosed patients. ..
  48. Kumps A, Vamos E, Mardens Y, Abramowicz M, Genin J, Duez P. Assessment of an electron-impact GC-MS method for organic acids and glycine conjugates in amniotic fluid. J Inherit Metab Dis. 2004;27:567-79 pubmed
    ..However, this method cannot replace procedures using isotopic internal standards, nor GC-MS based on chemical ionization fragmentation, which remain confirmatory analytical methods of choice. ..
  49. Pass K, Morrissey M. Enhancing newborn screening for tyrosinemia type I. Clin Chem. 2008;54:627-9 pubmed publisher
  50. Maydan G, Andresen B, Madsen P, Zeigler M, Raas Rothschild A, Zlotogorski A, et al. TAT gene mutation analysis in three Palestinian kindreds with oculocutaneous tyrosinaemia type II; characterization of a silent exonic transversion that causes complete missplicing by exon 11 skipping. J Inherit Metab Dis. 2006;29:620-6 pubmed
    ..1249C > T (R417X) exon 12 nonsense mutation (previously reported in a French patient) was identified in both patients from the third kindred, enabling successful prenatal diagnosis of an unaffected fetus using chorionic villous tissue...
  51. Dreumont N, Maresca A, Khandjian E, Baklouti F, Tanguay R. Cytoplasmic nonsense-mediated mRNA decay for a nonsense (W262X) transcript of the gene responsible for hereditary tyrosinemia, fumarylacetoacetate hydrolase. Biochem Biophys Res Commun. 2004;324:186-92 pubmed
    ..Cellular fractionation shows that this down-regulation of the W262X transcript occurs in the cytoplasm. Thus, the W262X FAH is another example of nonsense mRNAs subjected to the NMD pathway in the cytoplasm...
  52. Madan V, Gupta U. Tyrosinaemia type II with diffuse plantar keratoderma and self-mutilation. Clin Exp Dermatol. 2006;31:54-6 pubmed
    ..Emphasis is laid on the importance of early diagnosis and intervention in the form of dietary regulation to prevent the neurological signs and treat the oculocutaneous symptoms...
  53. Golbahar J, Karamizadeh Z, Honardar Z. Selective screening of amino acid disorders in the south-west of Iran, Shiraz. J Inherit Metab Dis. 2002;25:519-21 pubmed
    ..Minimum incidences, based on babies born between 1996 and 2001 inclusive, and diagnosed by the end of 2001, are 1:3672, 1:10651 and 1:21 303, respectively...
  54. Ferrer Bolufer I, Dalmau J, Quiroga R, Oltra S, Orellana C, Monfort S, et al. Tyrosinemia type 1 and Angelman syndrome due to paternal uniparental isodisomy 15. J Inherit Metab Dis. 2009;32 Suppl 1:S349-53 pubmed publisher
    ..The conclusion is that uniparental disomy should always be considered when more than one genetic disease mapping to the same chromosome is present in a patient...
  55. Cansever M, Aktuglu Zeybek A, Erim F. Determination of NTBC in serum samples from patients with hereditary tyrosinemia type I by capillary electrophoresis. Talanta. 2010;80:1846-8 pubmed publisher
    ..6 micromol/L for NTBC using UV detection at 278 nm. The utility of the method was demonstrated by the detection of NTBC in serum samples from patients with hereditary tyrosinemia type I using this drug...
  56. Nobili V, Vento S, Dionisi C, Sartorelli M, Russo C, Marcellini M. Acute liver failure as presenting feature of tyrosinemia type 1 in a child with primary HHV-6 infection. J Gastroenterol Hepatol. 2006;21:339 pubmed
  57. Yang D. 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. Drug News Perspect. 2003;16:493-6 pubmed
    ..Further application of the molecular mode of action of nitisinone in rational design of potential inhibitors for alpha-ketoglutarate-coupled dioxygenases is discussed...
  58. Devictor D, Tissieres P, Afanetti M, Debray D. Acute liver failure in children. Clin Res Hepatol Gastroenterol. 2011;35:430-7 pubmed publisher
  59. Boulat O, McLaren D, Arriaga E, Chen D. Separation of free amino acids in human plasma by capillary electrophoresis with laser induced fluorescence: potential for emergency diagnosis of inborn errors of metabolism. J Chromatogr B Biomed Sci Appl. 2001;754:217-28 pubmed
    ..Amino acid profiles for both normal donor plasma samples and plasma samples of patients suffering from phenylketonuria, tyrosinemia, maple syrup urinary disease, hyperornithinemia, and citrullinemia are studied...
  60. Rigante D, Gasbarrini A, Nista E, Candelli M. Decreased mitochondrial oxidative capacity in hereditary tyrosinemia type 1. Scand J Gastroenterol. 2005;40:612-3 pubmed
  61. Sass J, Skladal D. Elevated plasma bile acid concentrations in two sisters with tyrosinaemia type I. J Paediatr Child Health. 2000;36:91-3 pubmed
    ..This is the first report on altered bile acid concentrations in tyrosinaemia type I, and underlines the need for thorough investigation of bile acid metabolism in this disease...
  62. Han L, Ye J, Qiu W, Zhang H, Wang Y, Ji W, et al. [Application of succinylacetone levels measurement in the blood and urine in the diagnosis of tyrosinemia type 1]. Zhonghua Er Ke Za Zhi. 2012;50:126-30 pubmed
  63. Macsai M, Schwartz T, Hinkle D, Hummel M, Mulhern M, Rootman D. Tyrosinemia type II: nine cases of ocular signs and symptoms. Am J Ophthalmol. 2001;132:522-7 pubmed
    ..To report nine cases of tyrosinemia type II, with ocular signs and symptoms...
  64. Sandhu I, Maksim N, Amouzougan E, Gallion B, Raviele A, Ooi A. Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1). Biochem Soc Trans. 2015;43:650-6 pubmed publisher
    ..Biological insights gained from the hereditary syndromes' studies may shed light on to the roles of NRF2 activation in sporadic tumours. ..
  65. Hanauske Abel H, Popowicz A, Remotti H, Newfield R, Levy J. Tyrosinemia I, a model for human diseases mediated by 2-oxoacid-utilizing dioxygenases: hepatotoxin suppression by NTBC does not normalize hepatic collagen metabolism. J Pediatr Gastroenterol Nutr. 2002;35:73-8 pubmed
    ..13.11.27) and prolyl 4-hydroxylase (P4-H; E.C. 1.14.11.2), essential for tyrosine and collagen metabolism, respectively...
  66. Schauwvlieghe P, Jaeken J, Kestelyn P, Claerhout I. Confocal microscopy of corneal crystals in a patient with hereditary tyrosinemia type I, treated with NTBC. Cornea. 2013;32:91-4 pubmed publisher
    ..To describe the confocal microscopic findings in a patient with hereditary tyrosinemia type I (HT-I) treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) who developed corneal crystals...
  67. D Eufemia P, Finocchiaro R, Celli M, Raccio I, Properzi E, Zicari A. Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III. Biomed Pharmacother. 2009;63:359-61 pubmed publisher
    ..Considering the prominent expression of this enzyme in neurons, we hypothesize that excessive NO release could participate in neuronal damage explaining the neurological involvement described in patients with tyrosinemia type III...
  68. Hendriksz C, Walter J. Feeding infants with undiluted goat's milk can mimic tyrosinaemia type 1. Acta Paediatr. 2004;93:552-3 pubmed
    ..Undiluted goats milk should not be given to infants. High protein infant feeds are a forgotten cause of metabolic acidosis...
  69. Charfeddine C, Monastiri K, Mokni M, Laadjimi A, Kaabachi N, Perin O, et al. Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations. Mol Genet Metab. 2006;88:184-91 pubmed
    ..Phenotype variability was observed even among individuals sharing the same pathogenic mutation...
  70. David J, Tullu M, Rathi P, Sawalakhe N, Ghildiyal R. Neonatal presentation of a rare metabolic liver disease. Trop Gastroenterol. 2008;29:229-31 pubmed
    ..Very early neonatal presentation and rapid progression were the unusual features of this case...
  71. Sander J, Janzen N, Peter M, Sander S, Steuerwald U, Holtkamp U, et al. Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone. Clin Chem. 2006;52:482-7 pubmed
    ..We present our experience with a newly described method for succinylacetone quantification in routine newborn screening...
  72. Sivaraman S, Kirsch J. The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. FEBS J. 2006;273:1920-9 pubmed
  73. Wentzel J, Gouws C, Huysamen C, Dyk E, Koekemoer G, Pretorius P. Assessing the DNA methylation status of single cells with the comet assay. Anal Biochem. 2010;400:190-4 pubmed publisher
    ..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...
  74. Balciunas D, Wangensteen K, Wilber A, Bell J, Geurts A, Sivasubbu S, et al. Harnessing a high cargo-capacity transposon for genetic applications in vertebrates. PLoS Genet. 2006;2:e169 pubmed
    ..Together, Tol2 provides a novel nonviral vector for the delivery of large genetic payloads for gene therapy and other transgenic applications...
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    ..The novel assay was demonstrated to be accurate in the detection of newborns with IEM, robust, and above all, without the risk of the exposure to highly toxic reagents and requirement of additional equipment for toxic fume evacuation...
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    ..This demonstrates that early diagnosis of Richner-Hanhart syndrome is possible in neonates by extended newborn screening. Early introduction of dietary treatment is a prerequisite to reduce the risk of clinical symptoms...