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Case study (31) – Pyruvate Kinase Deficiency

Case study (31) – Pyruvate Kinase Deficiency 

A 34-year-old man has a history of chronic anemia that was improved by an operation at the age of 11. 

After moderate exercise, he feels tired and short of breath, but he does not need a blood transfusion and can cope well with daily activities. 

Medications include folic acid 5 mg/day and penicillin V 250 mg twice a day. 


Hemoglobin (Hb) 85 g/L 

Mean corpuscular volume (MCV) 107 f/L 


Q1. Comment on the blood film. 

Q2. Suggest the likely diagnosis. How would you confirm it? 


A1. The blood film showed irregularly contracted cells (pyknocytes) as well as Howell-Jolly corpses and target cells. 

Splenectomy is recommended, although the red blood cell abnormalities caused by splenectomy alone are beyond the usual abnormalities. 

A2. An important differential diagnosis is hereditary spherocytosis, but the blood film does not show spherocytes. 

Inherited glycolytic pathway enzymatic diseases are the most common. 

In this case, the diagnosis is pyruvate kinase deficiency. 

The automatic hemolysis test has historical and theoretical significance. 

Most laboratories will directly perform enzyme determinations and then perform DNA analysis to define specific mutations. 

Even so, this is a rare disease, with fewer than 300 cases reported worldwide. 

Red blood cells lack a nucleus and cannot perform protein synthesis to renew their insufficient supply of enzymes. 

Other tissues can also compensate, although neurological and cardiac complications can occur in hereditary red blood cell enzymopathies (e.g. triose phosphate isomerase deficiency). 

The levels of 2,3-diphosphoglycerate (2,3-DGP) are usually elevated in patients with pyruvate kinase deficiency and this leads to improved oxygen delivery to tissues and better tolerance of anemia. 

Another cause of congenital hemolytic anemia is the presence of an unstable hemoglobin variant (see image below). 

Although the alpha and gamma chain variants have been well described, these generally involve amino acid substitutions in the beta chain. 

Clinically, these disorders range from severe, with onset in early childhood, to mild, compensated hemolysis.