Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney

Abstract

Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. We describe dyserythropoiesis in the bone marrow of a child with transfusion dependent anemia and unilateral multicystic dysplastic kidney (MCDK) mimicking Congenital Dyserythropoietic Anemia type I (CDA type I). Persistently low erythrocyte PK levels and double heterozygous mutations present in the PKLR gene confirmed the diagnosis of PK deficiency.

A novel 33‐Gene targeted resequencing panel provides accurate, clinical‐grade diagnosis and improves patient management for rare inherited anaemias

“…Firstly, the risk of a wrong diagnosis is reduced given the practical and technical limitations of biochemical assays and EM interpretation without molecular confirmation. Indeed, our study shows that mis‐diagnosis of CDA‐I is fairly common, as the degree of bone marrow dyserythropoiesis in haemolytic conditions, although noted in previous case reports (Haija et al , 2014), remains under‐appreciated. Cases of CDA‐I submitted for molecular analysis were not felt to show CDA‐I‐ specific features when reviewed by our specialist pathologist, highlighting the difficulty of relying on morphological findings alone to make a diagnosis of CDA.…”

Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency

“…[70][71][72] The reticulocyte count in not-splenectomized patients is usually increased. In the most severe cases, some erythroblasts may be observed in peripheral blood smear as a consequence of ineffective erythropoiesis.…”

“…Dyserythropoietic features may also been observed at bone marrow examination, resulting in possible misdiagnosis with congenital dyserythropoietic anemias. [70][71][72] The reticulocyte count in not-splenectomized patients is usually increased. However, reticulocytosis is not proportional to the severity of hemolysis, likely due to a decreased erythropoietic drive since the oxygen delivery to tissues is relatively improved by the increase in 2, 3-DPG and because younger PK defective erythrocytes are selectively sequestered by the spleen.…”

Targeted next generation sequencing for the diagnosis of patients with rare congenital anemias

“…The erythroid morphology in the bone marrow is also nonspecific, and may show signs of dyserythropoiesis that can be misleading and suggest the wrongful diagnosis of congenital dyserythropoietic anemias. 18 In addition, analysis of the red blood cells enzymatic activity is no longer performed in many laboratories across the world, and therefore genetic analysis is the only modality to accurately diagnose patients with PK deficiency. Moreover, PK enzyme activity can be misleading in transfusion-dependent patients.…”

“…Nonetheless, an accurate diagnosis of DHS is of outmost importance, as splenectomy does not alleviate the hemolysis in these patients and is contra-indicated due to an increased risk for thromboembolic complications. [25][26][27] In our cohort, splenectomy was performed in 2 of the 4 patients ( 18,29 Diagnosing CDA in the bone marrow requires a highly experienced morphologist and is improved, especially in CDA I and II, by electron microscopy studies. [29][30][31] The high number of patients suspected to have CDA in this cohort might result from a selection bias resulting from our special interest in CDA.…”