HT-1 is an autosomal recessive genetic disorder (estimated birth prevalence: 1:100,000) caused by mutations in the gene responsible for formation of fumarylacetoacetate hydrolase (FAH), which catalyzes the last step in tyrosine metabolism. FAH deficiency results in accumulation of upstream toxic metabolites, causing liver and kidney failure and developmental delays. Before the advent of liver transplantation, HT-1 was invariably fatal, usually as a result of liver failure or hepatocellular carcinoma. Quebec, Canada, which has a relatively high incidence of HT-1, has screened newborns for the disorder since 1970.1

Nitisinone inhibits 4-hydroxyphenylpyruvate dioxygenase, preventing formation of upstream toxic metabolites. Started in infancy in combination with a tyrosine- and phenylalanine-restricted diet, it can prevent development of liver and kidney disease and the need for liver transplantation.2-4

The recommended starting dosage of nitisinone is 0.5 mg/kg twice daily. The dosage can be increased after one month to 0.75 mg/kg twice daily (max 1 mg/kg twice daily). A 30-day supply of Orfadin suspension for a child weighing 10 kg costs $13,623. Orfadin capsules can be opened and the contents can be mixed in a small amount of water, formula, or applesauce. A 30-day supply of Orfadin capsules (60 5-mg capsules) costs $12,499.5