Tyrosinemia type I is an autosomal recessive metabolic disorder, in which fumarylacetoacetate hydrolase (FAH), a key enzyme in the metabolism of tyrosine is missing. This defect leads to accumulation of tyrosine and its metabolites in the body, especially within the liver, causing complications. The acute form of the condition is characterized by diarrhea, vomiting, poor appetite, lethargy, jaundice, and a swollen liver, whereas the chronic form may present with polyneuropathy, kidney problems, intense abdominal pain, heart muscle weakness, and liver cirrhosis. If left untreated, the condition can lead to liver failure, growth failure, rickets, neurological crisis, and/or hepatocellular carcinoma, all in childhood. Although the incidence of this condition is generally less worldwide, some populations, like the French Canadian, may show an increased incidence.
Since the metabolic defect presents itself from birth, it is very important to diagnose it as early as possible, in order to prevent any damage. Increased excretion of succinylacetone in the urine is a major indicator of Type I Tyrosinemia. Other indications include elevated plasma concentrations of tyrosine, methionine and phenylalanine, and elevated urinary levels of other tyrosine metabolites. Diagnosis can also be made on the basis of assay of FAH enzyme activity from muscle fibroblasts, as well as molecular genetic testing of the FAH gene. Prenatal testing for succinylacetone or fumarylacetoacetate in the amniotic fluid is also possible. Once diagnosed, early intervention is imperative, to prevent any complications. Intervention is primarily in the form of dietary restrictions of tyrosine and phenylalanine. In addition, a drug called NTBC (Nitisinone) is also administered, which blocks the metabolic step that leads to the accumulation of fumarylacetotate and its conversion to succinylacetone. For severe cases, where the conditon has proceeded to liver cancer or severe liver damage, liver transplantation may be required.