Pyruvate kinase deficiency (PKD) is a rare genetic disorder characterised by haemolytic anaemia, which is the premature destruction of red blood cells.Disease symptoms are caused by malfunction of the enzyme pyruvate kinase. Pyruvate kinase plays a vital role in the critical energy-producing conversion of glucose into ATP via glycolysis. Abnormal red blood cells are gathered up by the spleen and destroyed, causing haemolytic anaemia and an enlarged spleen.Specifically, pyruvate kinase deficiency is a common cause of hereditary non-spherocytic haemolytic anaemia, where red blood cells fail to assume a spherical shape.
PKD is caused by mutations in the PKLR gene, which lead to a deficiency of the enzyme pyruvate kinase. The PKLR gene is active in the liver and in red blood cells, and mutations are inherited in an autosomal recessive manner, which means symptoms will only manifest in individuals that inherit copies of the mutated gene from both parents.
PKD is an incurable disease, and the choice of treatment will depend on the severity of the condition and the age at diagnosis. A foetus identified to have a low red blood cell count may need an intrauterine blood transfusion before birth, while newborns presenting with symptoms of PKD may need life-saving blood transfusions shortly after birth. Phototherapy is often used to treat the jaundice that occurs in newborns with PKD (due to a buildup of bilirubin in their blood).
For infants, children and adults living with PKD, treatment typically involves a combination of blood transfusions (in some cases this may occur frequently for the entire lifespan of an individual), folic acid supplements, chelation therapy to remove excess iron that can accumulate in the body, spleen and/or gallbladder removal, and a small-molecule medication (Pyrukynd, approved in US and EU in 2022) that functions as a puruvate kinase activator.
