A 27-year-old man complains of intermittent right upper quadrant pain that extends to the inferior tip of his scapula. Analysis of blood reveals mild anemia with the presence of normocytic and normochromic nonsperical erythrocytes. Additional blood work shows elevated levels of glucose 6-phosphate (G6P) and 2,3-bisphosphoglycerate (2,3BPG). Ultrasonic examination of the abdomen shows cholelithiasis. Following removal of her gallbladder, the stones are examined and shown to contain bilirubin. A deficiency in which of the following enzymes would most explain the signs and symptoms in this patient?

Question

Quizplus · Accepted Answer

The symptoms and lab findings suggest a hemolytic anemia due to pyruvate kinase deficiency, which leads to elevated levels of G6P and 2,3BPG, and can cause bilirubin gallstones due to increased hemolysis.  Deficiency of pyruvate kinase is the most common enzyme deficiency resulting in inherited nonspherocytic hemolytic anemia. The disorder is characterized by lifelong chronic hemolysis of variable severity. Red blood cells from heterozygous individuals possess only 40% to 60% of the pyruvate kinase activity of normal individuals yet these individuals are almost always clinically normal. The clinical severity of the anemia resulting from PKLR deficiencies varies from mild and fully compensated hemolysis to severe cases that require transfusions for survival. Many patients with mild PKLR deficiency do not manifest symptoms until adulthood. In these individuals, the symptoms, that include mild to moderate splenomegaly, mild chronic hemolysis, and jaundice often manifest incidental to an acute viral infection or during an evaluation in pregnancy. Clinical evaluation of blood from patients with PKLR deficiency will show normocytic anemia (sometimes macrocytic) which is reflective of the reticulocytosis that is invariably present. The hemolysis results in increased heme metabolism in the liver generating bilirubin in excess, which then accumulates in the gallbladder resulting in the stones present in this patient. The presence of elevated levels of serum 2,3BPG and G6P is indicative of anemia due to erythrocyte PK deficiency as opposed to the more common cause due to glucose-6-phosphate dehydrogenase deficiency. The reduced PK leads to increased levels of PEP, which are diverted into the 2,3BPG pathway.

A 27-Year-Old Man Complains of Intermittent Right Upper Quadrant Pain