Two sisters are diagnosed with hemolytic anemia. Their older brother was previously diagnosed with the same disorder. Two other brothers are asymptomatic. The mother and father are second cousins. Deficiency of which of the following enzymes would be most likely to cause this disorder?

A. Debranching enzyme
B. Glucose-6-phosphatase
C. Glucose-6-phosphate dehydrogenase
D. Muscle phosphorylase
E. Pyruvate kinase

C.

The correct answer is E. In general, you should associate hemolytic anemia with defects in glycolysis or the hexose monophosphate shunt (pentose phosphate pathway). Only two enzymes of those listed in the answer choices specifically involve these pathways and cause hemolytic anemia: pyruvate kinase and glucose-6-phosphate dehydrogenase. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is inherited as an X-linked recessive trait, so females would not be affected. Pyruvate kinase is a glycolytic enzyme; pyruvate kinase deficiency is an autosomal recessive disorder, affecting males and females approximately equally. If this enzyme is deficient, red cells have trouble producing enough ATP to maintain the Na+/K+ pump on the plasma membrane, secondarily causing swelling and lysis.
Debranching enzyme (choice A) defects produce Cori's disease, one of the glycogen storage diseases.

Defects in glucose-6-phosphatase (choice B) produce Von Gierke's disease, one of the glycogen storage diseases.

Glucose-6-phosphate dehydrogenase (choice C) deficiency produces an X-linked hemolytic anemia.

Defects in muscle phosphorylase (choice D) produce McArdle's disease, one of the glycogen storage diseases.