Children with tyrosinemia type I who escaped detection by newborn screening methods are generally identified during early infancy due to severe liver complications or even later during the first year of life due to liver dysfunction, kidney complications, a growth disorder, and rickets. If left untreated, tyrosinemia type I results in death within the first decade of life.
If it is not diagnosed or left untreated, tyrosinemia type I typically results in acute liver failure within the first 6 months of life. The first sign is the loss of the synthesis function of the coagulation factors. In contrast, the transaminases are only slightly elevated, and even the bilirubin level may be normal or only slightly elevated. This paradoxical combination distinguishes tyrosinemia type I from other severe liver diseases.
Furthermore, untreated children who have survived acute liver failure have a much higher risk of hepatocellular carcinomas.
Kidney complications in untreated children do not usually become evident until after the age of 6 months, when they manifest in the form of a dysfunction of the renal tubules. This leads to generalized aminoaciduria and phosphate loss, which can cause both rickets as well as renal tubular acidosis.
Untreated, children may exhibit repeated neurological crises that are similar to acute intermittent porphyria, with symptoms such as behavioral changes, abdominal pain, peripheral neuropathy, and respiratory dysfunction, the latter may even require ventilation.
The combination of nitisinone therapy and a tyrosine-reduced diet results in a survival rate > 90%, normal growth, improved liver function, the prevention of cirrhosis, the correction of renal tubular acidosis, and prevention of secondary rickets.
These have only been observed in patients following prolonged interruption of the treatment.
Acute liver failure usually improves within the first week after nitisinone therapy is started. The risk of a hepatocellular carcinoma is < 5% at the age of 10 in patients for whom nitisinone therapy was started before the age of 2.