Tyrosinemia type I

Tyrosinemia type I is a genetic disorder that disrupts the metabolism of the amino acid tyrosine and damages mainly the liver, along with the kidneys and peripheral nerves. It is an autosomal recessive condition caused by mutations in both copies of the gene for fumarylacetoacetate hydrolase (FAH), an enzyme made mostly in the liver and kidney. Without it, toxic intermediates accumulate, and the condition is diagnosed by finding raised succinylacetone in blood and urine. Infants typically present with failure to thrive and an enlarged liver, and progressive liver and kidney dysfunction can lead to cirrhosis, bleeding problems, Fanconi syndrome, rickets and a raised risk of liver cancer. Symptoms usually appear within the first two years of life, and earlier onset means more severe disease. There is no cure, but a lifelong diet low in tyrosine and phenylalanine plus the drug nitisinone allows normal growth and development when the disease is found early by newborn screening. It is especially common in the Saguenay-Lac-Saint-Jean region of Quebec, at about 1 in 1,850 births.