Tyrosinemia Clinical Presentation

  • Author: Karl S Roth, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Apr 13, 2012
 

History

Failure to thrive may precede the appearance of more dramatic findings in tyrosinemia. Patients with such findings often have a history of diminished nutritional intake and anorexia.

The patient then develops vomiting and diarrhea, which rapidly progress to bloody stool, lethargy, and jaundice. At this stage, a distinctive cabbagelike odor may be appreciated.

At approximately age 1 year, infants with the chronic form may have failure to thrive and delayed walking, which may indicate rickets.

Because the disease is autosomal recessive, the family pedigree typically does not reveal previously affected individuals. However, a French-Canadian ancestry should raise suspicion because of the extraordinarily high incidence of heterozygotes in the adult population of this lineage.

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Physical

Clinical suspicion should be extremely high in infants with failure to thrive and hepatomegaly in the first 3 months of life.

The acute onset may be dramatic, with hepatomegaly, jaundice, epistaxis, melena, purpuric lesions, marked edema, and the distinctive cabbagelike odor.

Because of the inhibitory effects of succinylacetone on the heme biosynthetic pathway, infants with the chronic form may develop polyneuropathy and painful abdominal crises, as seen in acute intermittent porphyria.

Survivors may have hepatic nodules and cirrhosis; the nodules may indicate hepatocellular carcinoma. Distant metastases can occur.

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Causes

The sole explanation for tyrosinemia I is genetic mutation in homozygous form. Heterozygote individuals are entirely unaffected.

The gene is mapped to band 15q23-q25, and approximately 30 distinct mutations have been reported, with no clear relationship between genotype and phenotype.

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Contributor Information and Disclosures
Author

Karl S Roth, MD  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 Clinical 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, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

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 American Society of Human Genetics

Disclosure: Nothing to disclose.

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.

Leonard G Feld, MD, PhD, MMM, FAAP  Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center

Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

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. Nov-Dec 2011;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. Aug 15 2001;10(17):1741-52. [Medline].

  3. 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. Mar 29 2012;[Medline].

  4. 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. Dec 2006;89(4):310-5. [Medline].

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

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

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

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

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

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

  11. 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].

  12. 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].

  13. 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. Jul 18 1981;114(1):37-44. [Medline].

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

  15. 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].

  16. 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. May 2003;92(5):625-8. [Medline].

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

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

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

  20. 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. Jul 2002;35(1):73-8. [Medline].

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

  22. 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].

  23. 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. May 26 1983;308(21):1265-7. [Medline].

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

  25. 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].

  26. 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].

  27. 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. Dec 2003;39(6):901-9. [Medline].

  28. 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. May 2006;88(1):16-21. [Medline].

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

  30. 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. Oct 24 1985;820(1):140-6. [Medline].

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

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

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

  34. 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). Jul 1992;83(1):81-7. [Medline].

 
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