The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism

The biochemical perturbations in children with inborn errors of metabolism (IEM) may affect their immune response. As a result, this will not only increase risk for infection but also hamper their ability to develop protective immunity after vaccination. Characterizing perturbations in immunity and the ability of vaccines to provide protective immunity in IEM is critical. Immune deficiencies and the immunogenicity of vaccines have not been well characterized in IEM. Viral infections play a significant role in precipitating life-threatening acute decompensations in various IEM. Seasonal variation of respiratory and gastrointestinal viruses places this vulnerable population at significant risk. The standard of care for these patients is routine childhood vaccination as well as vaccination for seasonal influenza viruses. However, nutritional deficiencies and their underlying IEM enzymopathies may affect the efficacy of vaccination. In this protocol, we will clinically evaluate the immunologic states of patients with IEM. Routine inpatient and outpatient admissions will last 2-3 days and may involve blood drawing, radiological procedures, nutrition assessment and biometrics. Immune challenge may be performed using vaccinations for seasonal influenza and pneumococcus (PPV23). Follow-up appointments will be scheduled at the end of the study period. The study objectives will be to describe the immune deficiencies seen, in this patient population, describe vaccine seroconversion in this patient population, and search for new genes in rare families that have evidence for an unknown class of IEM. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the patient advocacy groups. All patients will be evaluated at the NIH Clinical Center.