Clinical scenario: Severe liver dysfunction | Elevated plasma tyrosine levels
A 7-month-old infant is brought to the pediatric clinic with poor weight gain, recurrent vomiting, and increasing abdominal distension. The parents report that the child has become increasingly irritable and has had several episodes of unexplained bleeding. He was previously admitted at 3 months of age with severe liver dysfunction.
On examination, he has hepatomegaly, jaundice, and signs of rickets. Laboratory investigations reveal:
- Elevated serum α-fetoprotein
- Prolonged prothrombin time not corrected completely with vitamin K
- Elevated plasma tyrosine levels
- Metabolic acidosis
Which of the following is the most likely diagnosis?
A. Galactosemia
B. Hereditary fructose intolerance
C. Tyrosinemia type I
D. Alpha-1 antitrypsin deficiency
E. Wilson disease
Correct answer & Explanation:
Correct Answer: C. Tyrosinemia type I
Explanation
Tyrosinemia type I is an autosomal recessive amino acid metabolism disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH), the final enzyme in tyrosine degradation.
The toxic metabolites fumarylacetoacetate and succinylacetone accumulate, causing:
- Progressive liver injury
- Renal tubular dysfunction
- Neurological crises
- Increased risk of hepatocellular carcinoma
This infant has typical features:
- Hepatic failure in infancy
- Poor growth
- Hepatomegaly
- Coagulopathy
- Elevated alpha-fetoprotein (AFP)
- Rickets due to renal tubular dysfunction
- Elevated tyrosine levels
A key diagnostic marker is elevated urinary succinylacetone, which is specific for tyrosinemia type I.
Why the Other Options Are Incorrect
A. Galactosemia
- Causes neonatal jaundice, liver dysfunction, cataracts, and E. coli sepsis.
- Does not cause markedly elevated AFP or rickets.
B. Hereditary fructose intolerance
- Presents after introduction of fructose-containing foods.
- Causes vomiting, hypoglycemia, and liver dysfunction but not usually infancy-onset liver failure.
D. Alpha-1 antitrypsin deficiency
- Causes neonatal cholestasis and chronic liver disease.
- Does not cause renal tubular dysfunction or elevated tyrosine metabolites.
E. Wilson disease
- Usually presents later in childhood/adolescence.
- Low ceruloplasmin and copper accumulation are characteristic.
High-Yield Pearls
- Enzyme defect: Fumarylacetoacetate hydrolase (FAH)
- Inheritance: Autosomal recessive
- Diagnostic marker: ↑ Urinary succinylacetone
- Major complications:
- Acute/chronic liver failure
- Hepatocellular carcinoma
- Renal Fanconi syndrome
- Hypophosphatemic rickets
- Treatment:
- Nitisinone (NTBC) blocks upstream tyrosine metabolism
- Low-tyrosine/phenylalanine diet
- Liver transplantation in advanced disease
Exam Pearl
An infant with:
- Liver failure
- Coagulopathy
- High AFP
- Rickets
- Elevated tyrosine
→ Think Tyrosinemia type I.
