The primary treatment for<unk>  1<unk>  is nitisinone and restriction of tyrosine in the diet. Nitisinone inhibits the conversion of 4-OH phenylpyruvate to homogentisic acid by 4-Hydroxyphenylpyruvate dioxygenase, the second step in tyrosine degradation. By inhibiting this enzyme, the accumulation of the fumarylacetoacetate is prevented. Previously, liver transplantation was the primary treatment option and is still used in patients in whom nitisinone fails. Clinical treatment of HT1 relies on medications and strict regulation of diet. Nitisinone and dietary restrictions that decrease the amount of tyrosine and phenylalaine absorbed from the GI tract during protein digestion are used in combination as therapeutic measures that control the disease state if they are continued indefinitely. If not, there is a lack of control over the disease, resulting in continued liver and kidney damage, contributing to organ failure and death. In this case, a liver transplant may be required. Levels of SA are monitored throughout treatment in order to assess treatment effectiveness. Diet The prescribed diet for treatment of HT1 is low in protein. Patients received amino acid supplements lacking tyrosine and phenylalanine in order to acquire sufficient protein. It is recommended that tyrosine levels remain below 500 μmol/L. Phenylalnine is the precursor to tyrosine. The ideology behind maintaining low tyrosine levels is two-fold. Firstly, it prevents the toxic metabolic intermediates from accumulating as a result of the dysfunctional tyrosine metabolic pathway. Prior to the introduction of nitisinone, this was the main treatment measure. Secondly, the mechanism of action of nitisinone is prevention of any tyrosine metabolism, thus it is important to prevent tyrosine from accumulating. 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 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.
Tyrosinemia type I
Aspartylglucosaminuria
Hawkinsinuria
Aldolase A deficiency
Essential fructosuria
Transaldolase deficiency
Phenylketonuria
Cystathioninuria