Clinical Scenario:
A 6-month-old infant presents with failure to thrive, vomiting, and increasing abdominal distension. The parents report recurrent episodes of irritability and bleeding tendency. Examination reveals hepatomegaly. Laboratory investigations show elevated liver enzymes, coagulopathy, and increased serum alpha-fetoprotein. Urine analysis demonstrates elevated succinylacetone levels. Which of the following is the most appropriate treatment?
A) Dietary fructose restriction
B) Intravenous glucose infusion
C) Nitisinone therapy
D) Phenylalanine restriction
E) Vitamin B12 supplementation
Correct answer & Explanation:
Correct Answer:
C) Nitisinone therapy
Explanation:
This infant has Hereditary Tyrosinemia Type I, caused by deficiency of fumarylacetoacetate hydrolase (FAH), the final enzyme in tyrosine degradation.
The accumulation of toxic metabolites, especially fumarylacetoacetate and succinylacetone, causes:
- Progressive liver disease
- Coagulopathy
- Hepatomegaly
- Failure to thrive
- Renal tubular dysfunction
- Increased risk of hepatocellular carcinoma
Why Option C is correct:
Nitisinone (NTBC) inhibits 4-hydroxyphenylpyruvate dioxygenase, an upstream enzyme in tyrosine metabolism. This prevents formation of toxic downstream metabolites and is the standard treatment.
Additional management:
- Low-tyrosine and low-phenylalanine diet
- Monitoring for liver complications
Why other options are incorrect:
A) Dietary fructose restriction
- Used in hereditary fructose intolerance, not tyrosinemia.
B) Intravenous glucose infusion
- Used for acute metabolic decompensation in disorders such as fatty acid oxidation defects, but not definitive treatment here.
D) Phenylalanine restriction
- Used in phenylketonuria (PKU), although tyrosine is also restricted in tyrosinemia.
E) Vitamin B12 supplementation
- Used in some methylmalonic acid metabolism disorders, not tyrosinemia.
