Dietary protein consumption while taking nitisinone can also lead to side effects affecting the ocular system, which are easily reversed by removing protein from the diet. Medication
Nitisinone is prescribed ultimately to reduce the accumulation of toxic metabolic intermediates, such as succinylacetate, which are toxic to cells. It modifies the function of 4-hydrooxyphenylpyruvate dioxygenase by acting as a competitive inhibitor. 4-hydrooxyphenylpyruvate dioxygenase functions to convert 4-hydroxyphenylpyruvate to homogentisate as the second enzymatic reaction in the tyrosine catabolic pathway. This prevents the further catabolism of tyrosine. It is recommended that nitisinone treatment begins immediately following a confirmed or suspected case of HT1. It is supplied orally as a capsule or suspension in dose increments of 2 mg, 5 mg, 10 mg, or 20 mg or 4 mg/mL respectively. The starting dose is 1 mg/kg one time daily or 2 mg/kg one time daily for 48 hours if the patient is experiencing acute liver failure. Patient responsiveness to nitisinone is assessed by measuring blood coagulation activity and SA levels in blood and urine. Patients should display a positive response within 24–48 hours of first dose. Establishment of the long-term dosage will vary from patient to patient. It is recommended that nitisinone levels be maintained at 30-50 μM in the blood stream. Prognosis
Prior to the development of nitisinone, dietary restrictions and liver transplantation were the only forms of treatment for HT1.
Between 1963 and 1965, Swedish pediatrician Rolf Zetterström and colleagues at the Karolinska Institute in Sweden published the first detailed clinical account of hepatorenal tyrosinemia and its variants. Shortly thereafter, a Canadian group also described the clinical and laboratory findings of hepatorenal tyrosinemia. Both the Scandinavian and Canadian groups suggested that the Japanese patients described earlier by Sakai and colleagues had the same disorder, ie, hepatorenal tyrosinemia. In 1965, doubts emerged that the underlying biochemical cause of hepatorenal tyrosinemia was a defective form of the 4-hydroxyphenylpyruvate dioxygenase enzyme. In 1977, Bengt Lindblad and colleagues at the University of Gothenburg in Sweden demonstrated that the actual defect in causing hepatorenal tyrosinemia involved the fumarylacetoacetate hydrolase enzyme. This was subsequently confirmed using direct enzyme assays. Research directions
As of April 2020, two new clinical trials, are underway in the USA for a Mass Spectrometry-based biomarker for the early and sensitive diagnosis of Tyrosinemia type 1 from blood plasma. References
External links
Reference, Genetics Home. "Tyrosinemia". Genetics Home Reference. Retrieved 2020-05-01. "Tyrosinemia Type 1". NORD (National Organization for Rare Disorders). Retrieved 2020-05-01.