[Diagnosis of Congenital Hemolytic Anemias in Adults].
Source: PubMed, NCBI / U.S. National Library of Medicine
Hereditary hemolytic anemias (HHAs) are a heterogeneous group of genetic disorders characterized by the premature destruction of red blood cells due to intrinsic defects within these cells. In contrast to acquired forms, HHAs are caused by genetic variants affecting erythrocyte structure, function, or metabolism, leading to chronic hemolysis. Hemoglobinopathies, including thalassemias and sickle cell disease, represent the most prevalent HHAs worldwide and require combined analysis of hemoglobin fractions and genetic variants. Membranopathies, particularly hereditary spherocytosis, the most common form in Europe, are primarily identified using assays such as eosin-5-maleimide (EMA) binding and osmotic fragility testing. Enzymopathies, most notably pyruvate kinase and glucose-6-phosphate dehydrogenase deficiencies, necessitate a combination of enzymatic activity assays and confirmatory genetic testing. Advances in molecular diagnostics, especially next-generation sequencing, have substantially increased diagnostic yield by enabling parallel analysis of multiple genes and facilitating the identification of causative variants. This has important implications for establishing definitive diagnoses, guiding therapy, refining prognostic assessment, and enabling genetic counseling. Despite these advances, a subset of cases remains genetically unresolved, underscoring the need for continued research and expanded diagnostic strategies. Overall, this review highlights the central role o
Abstract
Hereditary hemolytic anemias (HHAs) are a heterogeneous group of genetic disorders characterized by the premature destruction of red blood cells due to intrinsic defects within these cells. In contrast to acquired forms, HHAs are caused by genetic variants affecting erythrocyte structure, function, or metabolism, leading to chronic hemolysis. Hemoglobinopathies, including thalassemias and sickle cell disease, represent the most prevalent HHAs worldwide and require combined analysis of hemoglobin fractions and genetic variants. Membranopathies, particularly hereditary spherocytosis, the most common form in Europe, are primarily identified using assays such as eosin-5-maleimide (EMA) binding and osmotic fragility testing. Enzymopathies, most notably pyruvate kinase and glucose-6-phosphate dehydrogenase deficiencies, necessitate a combination of enzymatic activity assays and confirmatory genetic testing. Advances in molecular diagnostics, especially next-generation sequencing, have substantially increased diagnostic yield by enabling parallel analysis of multiple genes and facilitating the identification of causative variants. This has important implications for establishing definitive diagnoses, guiding therapy, refining prognostic assessment, and enabling genetic counseling. Despite these advances, a subset of cases remains genetically unresolved, underscoring the need for continued research and expanded diagnostic strategies. Overall, this review highlights the central role of integrating specialized laboratory diagnostics with molecular genetic testing and supports an early, genetics-informed approach to optimize the diagnosis and management of HHAs in adult patients.