J Korean Med Sci.  2024 May;39(18):e162. 10.3346/jkms.2024.39.e162.

Current Status of Molecular Diagnosis of Hereditary Hemolytic Anemia in Korea

• Chueh HW
• Shim YJ
• Jung HL
• Kim N
• Hwang SM
• Kim M
• Choi HS
• on behalf of the Red Blood Cell Disorder Working Party of the Korean Society of Hematology

• KMID: 2555503
• DOI: http://doi.org/10.3346/jkms.2024.39.e162

Abstract

Hereditary hemolytic anemia (HHA) is considered a group of rare hematological diseases in Korea, primarily because of its unique ethnic characteristics and diagnostic challenges. Recently, the prevalence of HHA has increased in Korea, reflecting the increasing number of international marriages and increased awareness of the disease. In particular, the diagnosis of red blood cell (RBC) enzymopathy experienced a resurgence, given the advances in diagnostic techniques. In 2007, the RBC Disorder Working Party of the Korean Society of Hematology developed the Korean Standard Operating Procedure for the Diagnosis of Hereditary Hemolytic Anemia, which has been continuously updated since then. The latest Korean clinical practice guidelines for diagnosing HHA recommends performing nextgeneration sequencing as a preliminary step before analyzing RBC membrane proteins and enzymes. Recent breakthroughs in molecular genetic testing methods, particularly nextgeneration sequencing, are proving critical in identifying and providing insight into cases of HHA with previously unknown diagnoses. These innovative molecular genetic testing methods have now become important tools for the management and care planning of patients with HHA. This review aims to provide a comprehensive overview of recent advances in molecular genetic testing for the diagnosis of HHA, with particular emphasis on the Korean context.

Keyword

Anemia; Hemolytic; Congenital; Diagnosis; Genetic Testing

Figure

• 

  Fig. 1 Changes in the epidemiology of hereditary hemolytic anemia in Korea over three decades. Although membranopathy is predominant, there has been a marked increase in the detection rates of hemoglobinopathy and red blood cell enzymopathy as well.

• 

  Fig. 2 SOP for the diagnosis of HHA by the RBC Disorder Working Party of the KSH.515 HHA = hereditary hemolytic anemi, CBC = complete blood count, RBC = red blood cell, TIBC = total iron binding capacity, LDH = lactate dehydrogenase, EP = electrophoresis, PB = peripheral blood, OFT = osmotic fragility test, EMA = eosin 5-maleimide, HPLC = high-performance liquid chromatography, NGS = next-generation sequencing, SDS-PAGE = sodium dodecyl sulfate-polyacrylamide gel electrophoresis, WES = whole-exome sequencing, WGS = whole-genome sequencing, SOP = standard operating procedure, KSH = Korean Society of Hematology.*Prioritize enzyme analysis before transfusion in suspected patients; if unclear, perform NGS testing afterwards.

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