Figure 13-1The various levels of treatment that are relevant to genetic disease, with the corresponding strategies used at each level. For each level, a disease discussed in the book is given as an example. All the therapies listed are used clinically in many centers, unless indicated otherwise. Hb F, Fetal hemoglobin; mRNA, messenger RNA; PKU, phenylketonuria; RNAi, RNA interference; SCID, severe combined immunodeficiency. SeeSources & Acknowledgments.
Although powerful advances are being made, the overall treatment of single-gene diseases is presently deficient. A 25-year longitudinal survey of the effectiveness of treatment of 57 inborn errors of metabolism, reflecting the state of the field up to 2008, is shown in Figure 13-3. Note, however, that inborn errors are a group of diseases for which treatment is advanced, in general, compared to most other types of genetic disorders such as those due, for example, to chromosomal abnormalities, imprinting defects, or copy number variation. An encouraging trend over past decades is that treatment is more likely to be successful if the basic biochemical defect is known. In one study, for example, although treatment increased life span in only 15% of all single-gene diseases studied, life span was improved by approximately 50% in the subset of 57 inborn errors in which the cause was known; significant improvements were also observed for other phenotypes, including growth, intelligence, and social adaptation. Thus research to elucidate the genetic and biochemical bases of hereditary disease has a major impact on the clinical outcome.