eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Tyrosinemia: Differential Diagnoses & Workup

Author: Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Sep 1, 2009

Differential Diagnoses

Fructose 1,6-Diphosphatase Deficiency
Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)
Hepatitis B
Toxicity, Acetaminophen
Toxicity, Iron

Other Problems to Be Considered

Halothane anesthesia
Giant cell hepatitis
Other causes of acute hepatic failure

Workup

Laboratory Studies

  • Normocytic anemia and leukocytosis are characteristically present in tyrosinemia. Although the prothrombin time is increased, thrombocytosis may be present.
  • Serum bilirubin and transaminase levels are uniformly increased and the cholesterol level is low, signifying hepatocellular damage.
  • The alpha-fetoprotein level is increased, mirroring an increase seen in cord blood of newborns examined prospectively, even in the presence of tyrosine and methionine levels that are within the reference range.
    • Evidence suggests that hepatic damage does occur in utero; therefore, the clinical presentation of infantile tyrosinemia I actually represents the point at which liver damage has become so severe that hepatic decompensation occurs.
    • Increased plasma levels of tyrosine and methionine may simply indicate that this point has been reached.
    • Recent evidence suggests that, after the initiation of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) treatment, alpha-fetoprotein levels that rise, slowly decrease, or never normalize are all strongly associated with the subsequent development of hepatocarcinoma.2
  • Urinalysis may reveal alkaline pH, glucosuria, and proteinuria.
  • Urine chemistry reveals phosphaturia, glucosuria, and increased δ-aminolevulinic acid concentrations.
  • Quantitation of plasma amino acids in an early stage shows selective increases of tyrosine and methionine levels. As hepatic failure progresses, levels of most of the other amino acids become elevated.
  • Quantitation of urinary amino acids shows generally increased excretion of most or all amino acids (generalized aminoaciduria).

Imaging Studies

  • Imaging studies do not aid in diagnosis, except in cases of suspected hepatoma or hepatocellular carcinoma.

Other Tests

  • Urinary succinylacetone is the biochemical marker substance, and its presence is diagnostic for tyrosinemia I.
  • Proper collection and handling of the sample is of critical importance.

Procedures

  • No specific diagnostic procedures are indicated.

Histologic Findings

  • Active inflammation with fatty infiltration in the liver is evident.
  • Lobular regeneration is present and ultimately results in nodular cirrhosis.
  • Changes consistent with hepatoma may also be seen.
  • The kidney shows tubular swelling and formation of nodules, similar to that seen in the liver.

More on Tyrosinemia

Overview: Tyrosinemia
Differential Diagnoses & Workup: Tyrosinemia
Treatment & Medication: Tyrosinemia
Follow-up: Tyrosinemia
Multimedia: Tyrosinemia
References
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References

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  6. 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].

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Further Reading

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Keywords

tyrosinemia, hereditary infantile tyrosinemia, Richner-Hanhart syndrome, transient tyrosinemia of the newborn, TTN, tyrosinemia I, tyrosinemia II, tyrosinemia III, tyrosinosis, renal tubular dysfunction, Fanconi syndrome, liver failure, herpetiform corneal ulcers, hyperkeratotic lesions, ataxia, succinylacetone, nodular cirrhosis, hepatic cirrhosis, treatment, diagnosis

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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: MDS Pharma Salary Employment

Medical Editor

Erawati V Bawle, MD, FAAP, FACMG, Division of Genetic and Metabolic Disorders, Children's Hospital of Michigan; Professor (Clinician-Educator), Department of Pediatrics, Wayne State University School of Medicine
Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

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, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, 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.

 
 
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