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The most common side effects include decreases in estrone and estradiol (types of the estrogen hormone) in men, increased urate (a type of salt in the body), back pain, and joint stiffness. [ 3 ] Mitapivat was approved for medical use in the United States in February 2022, [ 1 ] [ 3 ] [ 4 ] [ 5 ] and in the European Union in November 2022. [ 2 ]
Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. [ 4 ] [ 5 ] Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive .
Pyruvate is then transported into mitochondria, where it is converted by the pyruvate dehydrogenase complex into acetyl-CoA, the starting substrate of the Krebs cycle. When PDC activity is reduced or abolished by mutation, pyruvate levels rise. Excess pyruvate is then converted into lactic acid by lactate dehydrogenase.
Mammals have two pyruvate kinase genes, PK-LR (which encodes for pyruvate kinase isozymes L and R) and PK-M (which encodes for pyruvate kinase isozyme M1), but only PKLR encodes for the red blood isozyme which effects pyruvate kinase deficiency. Over 250 PK-LR gene mutations have been identified and associated with pyruvate kinase deficiency.
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals.
In the United States, SIRVA was added to the list of compensable injuries on the Vaccine Injury Table used by the National Vaccine Injury Compensation Program in 2017. [6] [7] This inclusion allowed persons claiming an injury to seek compensation from a government fund set up under the program, while immunizing vaccine manufacturers and administrators from legal liability.
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