Metabolism as a complex genetic trait, a systems biology approach: Implications for inborn errors of metabolism and clinical diseases

Multifactorial and polygenic inheritance is commonly recognized for many genetic conditions including physical anomalies, complex congenital malformation syndromes, and even common disorders such as adult-onset diabetes mellitus. It has only recently been suggested as a mechanism for inheritance in inborn errors of metabolism. This article reviews the phenomenon of multiple partial enzyme deficiencies leading to clinical relevant biochemical derangements (synergistic heterozygosity) and its implications for other more common disorders such as diabetes and obesity.