Synergistic Heterozygosity: Undiagnosed Combination of Genetic Defects

Synergistic heterozygosity is a concept in genetics where heterozygous carrier status for multiple genes in one pathway or closely related pathways can synergize to produce a full-blown disease with no precise enzymatic or genetic diagnosis. This form of heterozygosity is likely far more common than traditional homozygosity for a single gene defect. Those with synergistic heterozygosity often present with mixed symptoms and diagnoses, making it difficult to recognize and diagnose. Traditional approaches to diagnosing inborn errors of metabolism often fail to uncover these cases, as each individual defect on its own is categorized as normal. Understanding synergistic heterozygosity may be critical to resolving confusing and intractable health problems, as well as optimizing overall wellness, performance, and longevity.