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Tyrosinemia Follow-up

  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Aug 13, 2015
 

Further Outpatient Care

Patients must be under the regular care of a biochemical geneticist and an experienced nutritionist.

Because of the low-phenylalanine, low-tyrosine diet, frequent quantitation of plasma amino acid levels is required. Adjustment is based on these results and on parameters of physical growth.

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Further Inpatient Care

Intercurrent illness in tyrosinemia may precipitate subsequent crises based on diminished intake, causing muscle protein catabolism with release of phenylalanine and tyrosine for energy.

Such crises require admission for treatment.

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Inpatient & Outpatient Medications

In addition to dietary treatment, the standard of care now requires use of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which prevents the formation of fumarylacetoacetate from tyrosine.[16]

Close monitoring of patients taking NTBC is essential, according to protocol requirements.

Subsequent, long-term experience with NTBC (nitisinone) has shown this agent to be very effective in both the acute phase of the disease, as well as in prevention of hepatic cellular carcinoma. In addition, children with initial renal tubular dysfunction show complete remission after long-term treatment with NTBC.[17, 18]

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Transfer

Immediately transfer any patient suspected of having tyrosinemia I to a major academic medical center, clinical status permitting.

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Deterrence/Prevention

Aside from treatment with NTBC, no other deterrents of disease onset are known.

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Complications

See the list below:

  • Hepatic cirrhosis
  • Renal Fanconi syndrome, including renal tubular acidosis type II
  • Rickets secondary to renal tubular acidosis (RTA)
  • Peripheral neuropathy
  • Abdominal crisis
  • Seizures
  • Hepatoma or hepatocellular carcinoma
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Prognosis

Without treatment, patients die from chronic hepatic failure by age 2 years. In the later-onset type, death from hepatic failure or hepatic tumor may occur in mid childhood.

Early liver transplantation poses the usual risks and complications of any major organ transplantation, including the risk of rejection.

Experience with NTBC has become more extensive; the drug appears to be effective in preventing progressive liver and renal disease and in aborting the fulminant clinical onset if started prior to age 1 month, a key reason for advocacy of adding this disorder to newborn screening panels in many places. The long-term results of NTBC therapy are emerging, and while early treatment appears very effective in eliminating cirrhosis and/or hepatomas, development in many affected children has been reported to be slower than normal.[19]

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Patient Education

Teach family members how to help the patient adhere to dietary restrictions and medication schedules.

Emphasize the importance of regular follow-up care with a biochemical geneticist.

Family members should understand that hepatic malignancy might develop despite all therapy. Medical follow-up care is imperative.

Prenatal diagnosis is possible for future pregnancies.

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Contributor Information and Disclosures
Author

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

References
  1. Iskeleli G, Bilgeç MD, Arici C, Atalay E, Ogreden T, Aydin A. Richner-Hanhart syndrome (tyrosinemia type II): a case report of delayed diagnosis with pseudodendritic corneal lesion. Turk J Pediatr. 2011 Nov-Dec. 53(6):692-4. [Medline].

  2. Jorquera R, Tanguay RM. Fumarylacetoacetate, the metabolite accumulating in hereditary tyrosinemia, activates the ERK pathway and induces mitotic abnormalities and genomic instability. Hum Mol Genet. 2001 Aug 15. 10(17):1741-52. [Medline].

  3. Bliksrud YT, Ellingsen A, Bjørås M. Fumarylacetoacetate inhibits the initial step of the base excision repair pathway: implication for the pathogenesis of tyrosinemia type I. J Inherit Metab Dis. 2013 Sep. 36(5):773-8. [Medline].

  4. Maiorana A, Malamisura M, Emma F, et al. Early effect of NTBC on renal tubular dysfunction in hereditary tyrosinemia type I. Mol Genet Metab. November 2014. 113:188-193. [Medline].

  5. Larochelle J, Alvarez F, Bussières JF, et al. Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec. Mol Genet Metab. 2012 Sep. 107(1-2):49-54. [Medline].

  6. Thimm E, Richter-Werkle R, Kamp G, et al. Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC. J Inherit Metab Dis. 2012 Mar. 35(2):263-8. [Medline].

  7. McKiernan PJ, Preece MA, Chakrapani A. Outcome of children with hereditary tyrosinemia following newborn screening. Arch Dis Child. August 2015. 100:738-741. [Medline].

  8. Bartlett DC, Preece MA, Holme E, Lloyd C, Newsome PN, McKiernan PJ. Plasma succinylacetone is persistently raised after liver transplantation in tyrosinaemia type 1. J Inherit Metab Dis. 2012 Mar 29. [Medline].

  9. Angeleri F, Bergeron A, Morrow, G, et al. Geographical and ethnic distribution of mutations of the fumarylacetoacetate hydrolase gene in hereditary tyrosinemia type I. JIMD Rep. 2015. 19:43-58. [Medline].

  10. Malik S, NiMhurchadha S, Jackson C, et al. Treatment adherence in type I hereditary tyrosinemia(HT1): a mixed-method investigation into the beliefs, attitudes and behavior of adolescent patients, their families and health-care team. JIMD Rep. 2015. 18:13-22. [Medline].

  11. Koelink CJ, van Hasselt P, van der Ploeg A, et al. Tyrosinemia type I treated by NTBC: how does AFP predict liver cancer?. Mol Genet Metab. 2006 Dec. 89(4):310-5. [Medline].

  12. Sniderman King L, Trahms C, Scott CR. Tyrosinemia type I(Internet). Gene Reviews{Internet}. July 2014. [Medline]. [Full Text].

  13. de Laet C, Dionisi-Vici C, Leonard JV, et al. Recommendations for the management of tyrosinaemia type 1. Orphanet J Rare Dis. 2013 Jan 11. 8:8. [Medline]. [Full Text].

  14. [Guideline] Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. 2005 Jun. 41(6):1407-32. [Medline].

  15. Nitisinone: new drug. Type 1 tyrosinemia: an effective drug. Prescrire Int. 2007 Apr. 16(88):56-8. [Medline].

  16. Schlune A, Thimm E, Herebian D, Spiekerkoetter U. Single dose NTBC-treatment of hereditary tyrosinemia type I. J Inherit Metab Dis. 2012 Feb 4. [Medline].

  17. Santra S, Preece MA, Hulton SA, McKiernan PJ. Renal tubular function in children with tyrosinaemia type I treated with nitisinone. J Inherit Metab Dis. 2008 Jun. 31(3):399-402. [Medline].

  18. Santra S, Baumann U. Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008 May. 9(7):1229-36. [Medline].

  19. Bendadi F, de Koning TJ, Visser G, et al. Impaired Cognitive Functioning in Patients with Tyrosinemia Type I Receiving Nitisinone. J Pediatr. 2013 Nov 14. [Medline].

  20. Ahmad S, Teckman JH, Lueder GT. Corneal opacities associated with NTBC treatment. Am J Ophthalmol. Aug 2002. 134(2):266-8. [Medline].

  21. Ashorn M, Pitkanen S, Salo MK, Heikinheimo M. Current strategies for the treatment of hereditary tyrosinemia type I. Paediatr Drugs. 2006. 8(1):47-54. [Medline].

  22. Barkaoui E, Debray D, Habes D, et al. [Favorable outcome of treatment with NTBC of acute liver insufficiency disclosing hereditary tyrosinemia type I]. Arch Pediatr. May 1999. 6(5):540-4. [Medline].

  23. Berger R, Smit GP, Stoker-de Vries SA, Duran M, Ketting D, Wadman SK. Deficiency of fumarylacetoacetase in a patient with hereditary tyrosinemia. Clin Chim Acta. 1981 Jul 18. 114(1):37-44. [Medline].

  24. Bijarnia S, Puri RD, Ruel J, et al. Tyrosinemia type I--diagnostic issues and prenatal diagnosis. Indian J Pediatr. 2006 Feb. 73(2):163-5. [Medline].

  25. Bruneau N, St-Vil D, Luks FI, et al. [Surgical and metabolic aspects of liver transplantation for tyrosinemia]. Ann Chir. 1993. 47(9):803-9. [Medline].

  26. Crone J, Moslinger D, Bodamer OA, et al. Reversibility of cirrhotic regenerative liver nodules upon NTBC treatment in a child with tyrosinaemia type I. Acta Paediatr. 2003 May. 92(5):625-8. [Medline].

  27. Endo F, Sun MS. Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells. J Inherit Metab Dis. 2002 May. 25(3):227-34. [Medline].

  28. Fisch RO, McCabe ER, Doeden D, et al. Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia. J Pediatr. 1978 Oct. 93(4):592-6. [Medline].

  29. Gartner JC Jr, Zitelli BJ, Malatack JJ, et al. Orthotopic liver transplantation in children: two-year experience with 47 patients. Pediatrics. 1984 Jul. 74(1):140-5. [Medline].

  30. Hanauske-Abel HM, Popowicz A, Remotti H, Newfield RS, 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 Jul. 35(1):73-8. [Medline].

  31. Heath SK, Gray RG, McKiernan P, et al. Mutation screening for tyrosinaemia type I. J Inherit Metab Dis. 2002 Oct. 25(6):523-4. [Medline].

  32. Holme E, Lindstedt S. Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione). J Inherit Metab Dis. Aug 1998. 21(5):507-17. [Medline].

  33. Hostetter MK, Levy HL, Winter HS, Knight GJ, Haddow JE. Evidence for liver disease preceding amino acid abnormalities in hereditary tyrosinemia. N Engl J Med. 1983 May 26. 308(21):1265-7. [Medline].

  34. Kvittingen EA, Jellum E, Stokke O. Assay of fumarylacetoacetate fumarylhydrolase in human liver-deficient activity in a case of hereditary tyrosinemia. Clin Chim Acta. 1981 Sep. 115(3):311-9. [Medline].

  35. Lindblad B, Lindstedt S, Steen G. On the enzymic defects in hereditary tyrosinemia. Proc Natl Acad Sci U S A. Oct 1977. 74(10):4641-5. [Medline].

  36. Lindstedt S, Holme E, Lock EA, et al. Treatment of hereditary tyrosinaemia type I by inhibition of 4- hydroxyphenylpyruvate dioxygenase. Lancet. Oct 3 1992. 340(8823):813-7. [Medline].

  37. Luijerink MC, Jacobs SM, van Beurden EA, et al. Extensive changes in liver gene expression induced by hereditary tyrosinemia type I are not normalized by treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). J Hepatol. 2003 Dec. 39(6):901-9. [Medline].

  38. Magera MJ, Gunawardena ND, Hahn SH, et al. Quantitative determination of succinylacetone in dried blood spots for newborn screening of tyrosinemia type I. Mol Genet Metab. 2006 May. 88(1):16-21. [Medline].

  39. McKiernan PJ. Nitisinone in the treatment of hereditary tyrosinemia type I. Drugs. 2006. 66(6):743-50. [Medline].

  40. Roth KS, Spencer PD, Higgins ES, Spencer RF. Effects of succinylacetone on methyl alpha-D-glucoside uptake by the rat renal tubule. Biochim Biophys Acta. 1985 Oct 24. 820(1):140-6. [Medline].

  41. Russo P, O'Regan S. Visceral pathology of hereditary tyrosinemia type I. Am J Hum Genet. 1990 Aug. 47(2):317-24. [Medline].

  42. Scott CR. The genetic tyrosinemias. Am J Med Genet C Semin Med Genet. 2006 May 15. 142(2):121-6. [Medline].

  43. Spencer PD, Roth KS. Effects of succinylacetone on amino acid uptake in the rat kidney. Biochem Med Metab Biol. 1987 Feb. 37(1):101-9. [Medline].

  44. Wyss PA, Boynton SB, Chu J, Spencer RF, Roth KS. Physiological basis for an animal model of the renal Fanconi syndrome: use of succinylacetone in the rat. Clin Sci (Lond). 1992 Jul. 83(1):81-7. [Medline].

 
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