Genetic Red Blood Cell Disorders

Genetic red blood cell disorders—resulting in abnormalities in the function, structure, or production of red blood cells—can cause anemia. Worldwide, approximately 11 percent of anemia is attributable to genetic red blood cell disorders, including the thalassemias and thalassemia trait, sickle cell disorders and sickle cell trait, glucose-6-phosphate deficiency (G6PD), other hemoglobinopathies and hemolytic anemias (Kassebaum and GBD 2013 Anemia Collaborators 2016), and Krüppel-like factor 1 variants (Perkins et al. 2016). All populations have genetic red blood cell disorders, but their contribution to the prevalence of anemia varies greatly both between and within different countries, even across small geographical distances (Kassebaum et al. 2014; Williams and Weatherall 2012). The highest instances are found in populations in or originating from Africa, the Middle East, and Asia. By different mechanisms, sickle cell disease, hemolytic anemias, and G6PD deficiency increase the destruction of red blood cells; while the thalassemias produce ineffective red blood cells, as well as a shorter red blood cell lifespan (Beutler 1996; WHO 2011).

Genetic red blood cell disorders are non-modifiable risk factors for anemia, but progress toward prevention and management of the thalassemias is reasonably well advanced in several countries in Asia (Fucharoen and Weatherall 2016). In many countries, the expertise and facilities for the control of genetic red blood cell disorders are extremely limited, but partnerships are being developed to improve control and treatment (Weatherall 2008; Fucharoen and Weatherall 2016).

How are genetic red blood cell disorders categorized?

Criteria for what constitutes a public health problem for genetic red blood cell disorders have not been established.

How are genetic red blood cell disorders measured?

DNA analysis is used to diagnosis genetic red blood cell disorders, but the current expense of DNA sequencing limits the use of this approach in population surveys (Perkins et al. 2016). At present, most population studies of genetic red blood cell disorders rely on phenotypic screening. For the thalassemias, the most common methods use identification of individuals with unusual red blood cell indices, followed by further analysis of abnormal samples by hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) (Weatherall et al. 2006). Osmotic fragility testing is a low-cost way to screen for the beta thalassemia trait, but it must be used with caution because the sensitivity may be limited by interactions with the carrier states for alpha thalassaemia, G6PD deficiency, and Southeast Asian Ovalocytosis (Penman, Gupta, and Weatherall 2014). Many hemoglobinopathies, including sickle hemoglobin (Hb S) disorders, Hb E, Hb C, and others, can also be identified by hemoglobin electrophoresis or HPLC. Enzyme testing is typically used to diagnose G6DP deficiency; a G6PD rapid diagnostic test is also available for use in the field (Espino et al. 2016).

Where can we get these data?

Most commonly administered population-based surveys do not collect or analyze information related to screening or diagnosing genetic red blood cell disorders. In recent years, however, the National Micronutrient Survey has started collecting information related to genetic red blood cell disorders, specifically in countries where these conditions are thought to be common.

Other resources are also available: The Gene database engine from the National Library of Medicine provides detailed information about all the disorders, including genetic basis, clinical condition, and prevalence in various populations. The International Genome Sample Resource, previously the 1000 Genomes Project, is an important source for data on variations in populations; the Ensembl genome browser can be used to search for genetic variation data; or the Frequency of Inherited Disorders database has information on the frequency of genetic variations across the world. However, you may need the services of a genetic epidemiologist to understand some of these data.

Methodological issues

  • Quantifying the contribution of genetic variants to anemia remains a challenge within the realm of public health because genes are expressed in many ways, and the expression can be modified by other factors like environment and diet.
  • More information on the contribution of genetic red blood cell disorders to anemia may be helpful when setting targets to reduce anemia.

Interventions that address genetic red blood cell disorders

  • Counseling and management of genetic blood disorders.

For more information about this intervention, go to the Step 4: Assessing Status of Anemia Interventions section.