Fritz Siegert, MD (2018)
Nominated From: University of Washington
Research Site: Uganda
Research Area: Hematology
Primary Mentor: Chandy John
Micronutrient deficiency in sickle cell anemia
Sickle cell anemia (SCA) is an inherited, recessive hemolytic anemia, defined by the presence of two mutated copies of the β-globulin gene producing hemoglobin S (HbSS). While individuals carrying only one copy of the HbS gene, sickle cell trait (HbAS), have increased resistance to malaria, thus explaining selection for the HbSS gene over time in malaria-endemic countries, individuals with SCA may suffer a higher malaria-caused mortality than either the HbAS or general population (HbAA). In deoxygenated conditions, caused by certain environmental insults/stressors, HbS rapidly polymerizes inducing a “sickling” effect in red blood cells (RBCs), leading to both intravascular and extravascular hemolysis. SCA is a multisystem disease: causing vaso-occlusive crises (VOC), increased susceptibility to blood borne infections, and chronic damage to many organ systems. Child deaths due to SCA are normally the result of acute anemia or infection, particularly sepsis and malaria.
SCA has a disproportionate disease burden in many African low-and-middle-income countries (LMICs) where malaria is endemic. In many African LMICs, the early-life mortality of those born with SCA is 5-16%. With increased monitoring and evaluation, it is anticipated that the detected incidence of newborns with SCA in sub-Saharan Africa will increase from just over 300,000 to over 400,000 by 2050. In Uganda, though reliable data is scarce, it is estimated that about 20,000 babies are born with SCA per year.
Undernutrition is common in SCA. Low micronutrient levels in SCA may be explained by 1) low dietary intake secondary to appetite suppression, caused by chronic inflammation and/or 2) high cell turn-over leading to increased macro- and micro-nutrient needs when compared to the general population. In particular, SCA has been associated with abnormal levels of vitamins B9 (folic acid), B12, A, D, and E. Previous research has also suggested an association between abnormal levels of these micronutrients and disease morbidity.
Significance and Relevance to the United States: The proposed study will provide novel data on micronutrients and sickle cell anemia (SCA) in an African population that suffers a high disease-burden of SCA. If micronutrient deficiency is common and associated with morbidity, this study will set the stage for future trials of micronutrient supplementation in African children with SCA that cold also benefit people with SCA living in the United States and other parts of the world where SCA is prevalent.
Aim 1: Define prevalence of micronutrient deficiency in a cohort of Ugandan children
Aim 2: Determine if micronutrient deficiency is associated with morbidity in Ugandan children with SCA
Aim 3: Determine the effect of hydroxyurea therapy on micronutrient levels
- Dr. Chandy John, Indiana University
- Dr. Robert Opoka, Makerere University, Uganda
- Dr. Russel Ware, Cincinnati Children’s Hospital
- Dr. Heather Hume, University of Montreal
- Dr. Ruth Namazzi, Makerere University