Retrospective Pharmacogenetic Study in a Cohort of Pediatric Tuberous Sclerosis Complex Patients Using Everolimus

Tuberous sclerosis complex (TSC) is a rare disease that produces multisystemic disorders. Everolimus (EVR) is the only immunosuppressive drug approved to control the symptoms and progression of the disease. The aim was to evaluate the genotype-phenotype association to improve the pediatric TSC pharmacotherapeutic outcome. Ten pediatric TSC patients were recruited. Concomitant treatment and main metabolic enzymes and transporter coding gene variants of EVR were analyzed. Significant associations were found between allele and concomitant treatment with valproic acid (CYP3A4-inhibitor) with a poor metabolizer phenotype and the presence of pneumonia. This is the first pharmacogenetic study of EVR in pediatric TSC patients. The authors propose to consider concomitant treatment and pharmacogenetics due to their multifactorial status.