Down syndrome (DS) is associated with aberrations in genetic, morphological, biochemical and physiological characteristics. A number of genes located on human chromosome 21 (HSA21) encode proteins which are thought to be involved in numerous metabolic pathways, e.g., phosphofructokinase, cystathionine β-synthase etc. Perturbations of the metabolic pathways may lead to altered drug metabolism in DS individuals. We present a review of metabolic aberrations linked to HSA21 genes in DS. We particularly focus on drug disposition, efficacy, sensitivity and toxicity of anti-leukaemic agents including methotrexate, glucocorticoids, anthracyclines and cytarabine in DS leukaemia. The different outcomes of therapy due to differential drug response, varied drug toxicity and treatment related mortality in DS leukaemia is a subject of much research and speculation. Altered drug response in DS individuals may stem from differences in pharmacokinetics, pharmacodynamics and pharmacogenetics. Further large-cohort studies in different age groups dissecting metabolic and molecular pathways involved in drug response may increase our understanding in this regard and stipulate pharmacotherapies in DS.
The Hay-flick Limit is a concept that helps to explain the mechanisms behind cellular aging. The concept states that a normal human cell can only replicate and divide forty to sixty times before it cannot divide anymore, and will break down by programmed cell death or apoptosis.
