Objective: Objective: Pyruvate kinase (PK) deficiency is the most common enzyme abnormality in the glycolytic pathway, which leads to an anemia secondary to decreased ATP synthesis. The disease exhibits autosomal recessive inheritance and is caused by mutations in the PKLR gene. The diagnosis of PK deficiency is based on the presence of clinical signs and symptoms of hemolytic anemia, evidence of extravascular hemolysis on laboratory findings, measurement of the PK activity or antigen levels and detection of mutations in the PKLR gene.

Methodology: Here, we describe two siblings with PK deficiency that was misdiagnosed as congenital dyserythropoietic anemia (CDA) type I.

Results: Cases: The siblings were referred to our hospital for the evaluation of the anemia when they were newborn. On physical examination, they both had an icteric appearance. Their PK, glucose-6-phosphate dehydrogenase and 5’ nucleotidase enzyme activities, hemoglobin electrophoresis and osmotic fragility test were normal. Erythroid hyperactivity with many bi-multilobed erythroblasts, which raised the concern of CDA, was seen in bone marrow aspiration. Spongy appearance (Swiss cheese appearance) of heterochromatin in all normoblasts and expansion of the perinuclear areas and the extension of the cytoplasm towards the nucleus in some, were observed with electron microscopy. CDA panel by next generation sequencing showed no mutation. Though their PK enzyme levels were normal, the molecular study of PKLR gene, a homozygote variant c.1623G>C (p.Lys541Asn) in exon 12 was found in our patients.

Conclusion: Discussion: Pyruvate kinase deficiency is a rare cause of hemolytic anemia and given to the rarity and the clinical heterogeneity, the diagnosis of PK deficiency can be difficult, mostly in atypical forms. PK deficiency should be considered in the differential diagnosis of CDA. Instead of the enzyme activity, comprehensive genetic analysis is warranted more effective diagnosis of patients with suspected CDA and congenital hemolytic anemia.