Hereditary tyrosinemia type 1 (HT-1) is a rare, autosomal recessive disorder of amino acid metabolism. The deficiency of fumarylacetoacetate hydrolase (FAH), which is the last enzyme in the pathway of tyrosine catabolism, results in the accumulation of toxic metabolites in the FAH-deficient hepatocytes and proximal renal tubular cells, and subsequently leads to liver and kidney damage. HT-1 typically manifests in infancy and is characterized by elevated plasma tyrosine levels. For children whose HT-1 is not detected by the newborn screening, liver dysfunction, such as bleeding abnormalities, hypoglycemia, ascites, edema, vomiting, irritability, and jaundice, is the dominant clinical manifestation. Progression of the liver disease can be chronic or acute, with rapid deterioration. The lifetime risk of developing hepatocellular carcinoma (HCC) is as high as 37% in the survivors without treatment, according to previous research. Many patients also suffer from neurocognitive deficits. If untreated, survival in patients with HT-1 is less than 12 months of life; most of these children die as a result of liver failure and severe coagulopathy. The prevalence of HT-1 ranges from one in 12,000 to one in 100,000 individuals of Northern European descent. In Canada, higher prevalence (one in 1,846 live births) was observed in the Saguenay–Lac Saint-Jean region in Quebec.

Without treatment, death in childhood is common. Before the introduction of nitisinone, the management of HT-1 involved dietary restriction of phenylalanine and tyrosine, along with supportive treatment, until liver transplantation if possible. At present, all affected children are managed with nitisinone in combination with a tyrosine- and phenylalanine-restricted diet. Liver transplantation remains the only definitive therapy for patients with HT-1, when the patients do not respond to nitisinone therapy and there is progressive liver failure, or they have suspected HCC. However, liver transplantation is associated with risks of operative complications, including death, graft rejection, and the challenge of organ availability.

Nitisinone (MDK-Nitisinone) is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase, an enzyme upstream of FAH in the tyrosine catabolic pathway. It prevents the accumulation of the catabolic intermediates, which can be converted to the toxic metabolites SA and succinyl acetoacetate. The effect of nitisinone on inhibiting catabolism of tyrosine also leads to an increase in plasma tyrosine levels. Therefore, treatment with nitisinone requires restriction of the dietary intake of tyrosine and phenylalanine to prevent tyrosine toxicity.