Tyrosinemia Workup

Updated: Jun 02, 2021
  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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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. 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. [15]

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. Plain films of wrists and knees may be of help in diagnosis of rickets, secondary to the renal tubular acidosis component of the Fanconi syndrome.


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.

Neonatal screening programs in many areas are capable of detecting succinylacetone in submitted blood samples.

Molecular diagnosis is available and can detect the 4 most common mutations, which account for more than 95% of cases. This technique also enables prenatal diagnosis. [16]



No other 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.