Pyruvate Kinase Deficiency
Pyruvate kinase deficiency (PKD) is one of the most common enzymatic defects of the RBCs, it manifests clinically as hemolytic anemia that can range from mild to severe. There are many different types of enzyme-related defects of the red blood cell that can cause hemolytic anemia. PKD is the second most common cause, after glucose-6-phosphate dehydrogenase (G6PD) deficiency.
PKD is inherited in an autosomal recessive pattern. PKD is found in people of all ethnic backgrounds. But, certain populations, such as the Amish, are more likely to develop the condition.
PKD is characterized by low levels of an enzyme called pyruvate kinase, which is used by red blood cells. Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells (hemolytic anemia).
The birth history of patients with PKD includes severe anemia, severe jaundice, kernicterus, and history of exchange transfusion.
The signs and symptoms of PKD may vary greatly from person to person. However, they usually include jaundice, enlargement of the spleen, and mild or severe hemolysis (red cell breakdown), leading to anemia. Anemia could be normocytic or macrocytic. In some cases, the problems may first appear while in utero, causing a condition in which abnormal amounts of fluid build up in two or more body areas of the fetus (hydrops fetalis). Newborns may present with prolonged jaundice and anemia. Older children may be pale (due to anemia) and have intermittent episodes of jaundice. Mild cases may escape detection until adulthood. Although the anemia tends to stabilize in adulthood, episodes of anemia may occur with acute infections, stress, and pregnancy. Pyruvate kinase deficiency is caused by a mutation in the PKLR gene and is inherited in an autosomal recessive fashion.
Growth delay and failure to thrive
Gall bladder stones: usually after the first decade of life but possibly in childhood
Hyperbilirubinemia in the newborn
Raised serum LDH
Mild to moderate splenomegaly
Chronic leg ulcers (adults)
Differential blood count
Direct Coomb’s test (to exclude immune hemolysis)
Peripheral blood film examination
Normoblastic erythroid hyperplasia of the bone marrow
The enzyme activity rate in most patients with PKD is 5-25% of normal.
In patients with mild to moderate pyruvate kinase deficiency, care is predominantly supportive.
Some physicians may advise oral folic acid daily. Folic acid is a vitamin needed by the bone marrow to make new red blood cells.
Typically, severe anemia is treated with blood transfusions. Some people with PKD require transfusions every 3 to 4 weeks. Other people may only require transfusions occasionally during times of illness or stress, but others may never require transfusion.
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