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: Hereditary Tyrosinemia Type I
This infant has hereditary tyrosinemia type I (HT-1), an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH), the final enzyme in the tyrosine degradation pathway.
FAH deficiency causes accumulation of toxic metabolites, particularly fumarylacetoacetate and succinylacetone, resulting in progressive liver disease, renal tubular dysfunction, growth failure, and an increased risk of hepatocellular carcinoma.
Why Option C is correct
Nitisinone (NTBC) inhibits 4-hydroxyphenylpyruvate dioxygenase, an enzyme upstream of the FAH defect. This blocks the formation of toxic downstream metabolites such as fumarylacetoacetate and succinylacetone.
Nitisinone should be combined with a low-tyrosine and low-phenylalanine diet. Early treatment markedly improves the prognosis and reduces liver and renal complications.
Why the other options are incorrect
A) Dietary fructose restriction
Used in hereditary fructose intolerance, not hereditary tyrosinemia type I.
B) Intravenous glucose infusion
May be used as supportive treatment during acute metabolic decompensation in some metabolic disorders, but it does not correct the underlying metabolic defect in HT-1.
D) Phenylalanine restriction
Phenylalanine restriction is part of the dietary management of HT-1, but diet alone is not the definitive treatment. Nitisinone is the key pharmacological therapy.
E) Vitamin B12 supplementation
Used in selected disorders of intracellular cobalamin metabolism, such as some forms of methylmalonic acidemia, and has no role as definitive therapy for HT-1.
High-Yield Exam Pearl
Hereditary tyrosinemia type I → FAH deficiency → succinylacetone accumulation → nitisinone + low-tyrosine/low-phenylalanine diet.
Diagnostic clue: Succinylacetone is the characteristic biochemical marker of HT-1.
Reference
Das AM, Ballhausen D, Haas D, et al. Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries. J Inherit Metab Dis. 2024.
You can also practice another MCQ on Recurrent Renal Stones.
