A study regarding the efficacy of treatment with nitisinone and dietary restrictions found that 93% of people survived at two years, four years, and six years indicating the prognosis of stabilizing the HT1 disease state is positive. Epidemiology
Tyrosinemia type I affects males and females in equal numbers. Its prevalence has been estimated to be 1 in 100,000 to 120,000 births worldwide. HT1 is especially prevalent in the Saguenay-Lac Saint-Jean region of Quebec is one in 1,850 births. The elevated frequency of this disorder within individuals of French-Canadian ancestry in Quebec is believed to be due to reduced genetic heterogeneity within the original founder population for the Saguenay-Lac Saint-Jean region. The initial settlement of Saguenay Lac-Saint-Jean (SLSJ) occurred between 1838 and 1911. From a total of 28,656 settlers, 75 percent originated from the neighboring Charlevoix region. The settling of the Charlevoix region itself started in 1675 when 599 founders of mostly French descent moved to this region from the Quebec City area.Worldwide, type I tyrosinemia affects about 1 person in 100,000. This type of tyrosinemia is much more common in Quebec, Canada. The overall incidence in Quebec is about 1 in 16,000 individuals. In the Saguenay-Lac-Saint-Jean region of Quebec, type 1 tyrosinemia affects 1 person in 1,846. The carrier rate has been estimated to be between 1 in 20 and 1 in 31. History
Nitisinone was first used to clinically treat tyrosinemia type I in 1991. Nitisinone was approved by the European Medicine Agency (EMA) under exceptional circumstances in 2005.
This means a defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. Pathophysiology
At present, no specific enzyme deficiency nor genetic mutation has been implicated as the cause of hypertryptophanemia. Several known factors regarding tryptophan metabolism and kynurenines, however, may explain the presence of behavioral abnormalities seen with the disorder.Tryptophan is an essential amino acid, and is required for protein synthesis. Aside from this crucial role, the remainder of tryptophan is primarily metabolized along the kynurenine pathway in most tissues, including those of the brain and central nervous system.As the main defect behind hypertryptophanemia is suspected to alter and disrupt the metabolic pathway from tryptophan to kynurenine, a possible correlation between hypertryptophanemia and the known effects of kynurenines on neuronal function, physiology and behavior may be of interest.One of these kynurenines, aptly named kynurenic acid, serves as a neuroprotectant through its function as an antagonist at both nicotinic and glutamate receptors (responsive to the neurotransmitters nicotine and glutamate, respectively). This action is in opposition to the agonist quinolinic acid, another kynurenine, noted for its potential as a neurotoxin.