Pyruvate kinase (PK) deficiency is an autosomal recessive red blood cell (RBC) enzymopathy leading to chronic hemolysis. It is the second most common RBC enzymopathy and the most frequent cause of chronic hemolytic anemia due to an enzyme defect. PK enzymes consist of various isoforms encoded by PKLR and PKM genes, which catalyze the conversion of phosphoenolpyruvate (PEP) to pyruvate and ATP in the final step of glycolysis. Clinically significant PK deficiency is associated with PKLR mutations. Acquired PK deficiency is extremely rare, and its molecular basis remains unclear. Some cases have been associated with AML. Here we present a rare case of acquired PK deficiency followed by myelodysplastic syndrome (MDS).

A 70-year-old male presented with fatigue, weakness, and jaundice. Laboratory findings were as follows: WBC: 7.0 × 10⁹/L, Hemoglobin: 7.9 g/dL, MCV: 101 fL, Platelets: 601 × 10⁹/L, Total bilirubin: 1.6 mg/dL (indirect: 1.0 mg/dL), LDH: 280 U/L. Other biochemical parameters were within normal limits. Hemoglobin electrophoresis was normal. Direct and indirect Coombs tests were negative. Haptoglobin was 14 mg/dL (low). Erythrocyte PK activity was reduced at 3.16 U/g Hb (reference: 4.4–5.9). G6PD activity and osmotic fragility were normal.

The patient had no prior anemia history. Genetic analysis for PKLR mutations was negative, supporting an acquired form. During follow-up, bilirubin increased to 8.6 mg/dL, LDH rose to 800 U/L, and hemoglobin decreased to 6.0 g/dL. The patient was taking gliclazide for diabetes mellitus, which was discontinued due to suspicion of hemolysis induction. Bilirubin subsequently decreased. Bone marrow biopsy showed dysplastic erythroid changes without blast increase, consistent with MDS. The patient initially required two RBC transfusions weekly, but after gliclazide withdrawal, the requirement decreased to one unit every two weeks. Genetic testing for MDS is ongoing.

Acquired PK deficiency is extremely rare. In this case, a 70-year-old patient developed PK deficiency followed by a diagnosis of MDS. While congenital hemolytic anemias usually present in younger patients, clinicians should be aware that acquired cases may appear later in life. Careful evaluation of medications and bone marrow disorders is essential in elderly patients with unexplained hemolysis.