It is generally accepted that children and adolescents with homozygous sickle cell disease experience impairment in physical growth during childhood and adolescence. Nutrition has been con-sidered a possible contributor to this delay. Energy metabolism, protein metabolism, and retinol, folic acid, zinc, and iron status have been reported to be deficient in patients with sickle cell disease. Growth retardation in adolescents with homozygous sickle cell disease, however, cannot be explained solely on the basis of decreased intake or absorption of nutrients and protein. Amounts sufficient for growth in a normal adolescent may be insuf-ficient for the increased metabolic needs of individuals with sickle cell anemia [Hemoglobin (Hb) SS genotype - HbSS]. Nitrogen balance, for example, in adolescents with SCD responds differently to changes in dietary nitrogen when compared to healthy individuals. HbSS is a hypercatabolic condition in which rate of erythrocyte destruction is higher than normal and causing basal metabolic rate to increase. The increase in energy metabolism rate is caused by the energy cost of higher protein turnover. As a result, resting energy expenditure is elevated. Other components of total energy expenditure such as energy losses (EL) or thermal effect of food (TEF) most likely remain un-changed, although no proof exists. Energy expenditure for physical activity and work (EEact) in subjects with HbSS has not been reported and, therefore, is unknown. In the proposed studies. For the first time, all components of energy expenditure and total 24 h energy balance will be measured simultaneously and continuously in HbSS adolescents and adults living inside a whole-room indirect calorimeter in a semi-naturalistic environment in combination with stable isotope techniques to measure protein metabolism. The secondary focus of this proposal is to determine the potential of increased rates of protein synthesis, protein breakdown and amino acid oxidation to modulate energy expenditure in individuals with HbSS. Energy and nutrient intake will be also assessed, and nitrogen balance will be measured in all subjects. In addition, the effect of physical activity and work on energy expenditure and balance will be evaluated. Age-, sex-, weight-, and high-matched healthy individuals. [Hemoglobin (Hb) AA genotype - HbAA]. from similar socio-economic environments will serve as controls in all experiments. Findings from these studies will enhance our understanding of the relationship between energy intake, energy expenditure, and protein metabolism in homozygous sickle cell disease, and may help to define optimal energy and nitrogen intake in HBSS patients. As a result, these studies may be of immediate relevance to the clinical management of the HbSS patient.
