Updates on clinical and laboratory aspects of hereditary dyserythropoietic anemias

Hereditary dyserythropoietic anemias, or congenital dyserythropoietic anemias (CDAs), are rare disorders disrupting normal erythroid lineage development, resulting in ineffective erythropoiesis and monolinear cytopenia. CDAs include three main types (I, II, III), transcription-factor-related forms, and syndromic forms. The widespread use of next-generation sequencing in the last decade has unveiled novel causative genes and unexpected genotype–phenotype correlations. The discovery of the genetic defects underlying the CDAs not only facilitates accurate diagnosis but also enhances understanding of CDA pathophysiology. Notable advancements include identifying a hepatic-specific role of the SEC23B loss-of-function in iron metabolism dysregulation in CDA II, deepening CDIN1 dysfunction during erythroid differentiation, and uncovering a recessive CDA III form associated with RACGAP1 variants. Current treatments primarily rely on supportive measures tailored to disease severity and clinical features. Comparative studies with pyruvate kinase deficiency have illuminated new therapeutic avenues by elucidating iron dyshomeostasis and dyserythropoiesis mechanisms. We herein discuss recent progress in diagnostic methodologies, novel gene discoveries, and enhanced comprehension of CDA pathogenesis and molecular genetics.