Abstract
There is a desperate need to make genomic medicine, especially diagnosis for the undiagnosed, available to all individuals regardless of their social status, income, or geographic location. Across the globe, more than ∼7000 genetic conditions have been well described, affecting at least 250 million people. Almost three-quarters of these conditions are present in childhood, and up to 50% of these children will die before the age of 5 years (Wakap et al., 2020). In the United States, it has been estimated that although only ∼14% of hospitalizations are associated with a patient with a genetic disease, they account for ∼50% of the national health care bill (Gonzaludo et al., 2019).
In geographies where the historical burden of early onset communicable diseases is decreasing, including parts of Africa, genetic diseases will become the next leading cause of infant mortality (Holmes et al., 2010). According to a publication by Holmes et al., the insurgence of noninfectious diseases is a “time bomb” for Africa. The region is expected to record the world's largest increase in noninfectious disease deaths by 2030 (Holmes et al., 2010). The World Health Organization (2014) states that countries in northern and southern Africa account for more than three quarters and close to half of all deaths to noninfectious diseases, respectively.
The most potent tool in genomic medicine is clinical whole genome sequencing (cWGS). As more laboratories adopt cWGS and the cost decreases, it is essential to review the diagnostic yield and health economics of this as a testing modality, particularly for low- to middle-income countries (LMICs), as defined by the World Bank Atlas Method. Until recently, most people affected by genetic diseases had little hope of a diagnosis—often seeing dozens of specialists and spending tens of thousands of dollars on ineffective tests and treatments (Bick et al., 2019). Delay in diagnosis leads to ever-increasing disability and mortality and an enormous impact on the family, particularly women who represent the majority of care givers.
However, the advent of genomic sequencing technologies, particularly whole genome sequencing in the clinical context, has revolutionized care or the potential for care for these children. Diagnostic success rates have expanded from a few percent to up to 70%, leading to changes in clinical management in 50-70% of cases (Scocchia et al., 2019). In addition, genetic disease was 5 × more likely to be identified by cWGS than microarray and gene panels (42% vs. 10%, respectively) in infants with congenital heart defects, representing the most common congenital anomaly and the primary cause of mortality and morbidity (Sweeney et al. 2021).
In addition to looking at the diagnostic yield, it is important to review the cost savings achieved by performing cWGS. A study published by Rady Children's Institute for Genomic Medicine showed that rapid cWGS prevented morbidity in 11 out of 18 diagnosed infants (61%) compared with none from the standard of care. In addition, the cost of care for six of the infants was reduced by at least $803,200 (Farnaes et al. 2018).
Economic modeling conducted by Incerti (2022) resulted in genomic sequencing being cost neutral or possibly cost saving as a first-line diagnostic tool for children and critically ill infants. Also, a study from the Murdoch Children's Institute showed that whole exome sequencing in children with suspected monogenic conditions has high diagnostic yield, and cost-effectiveness is maximized by early application in the diagnostic pathway (Stark et al., 2019).
cWGS can impact care outcomes while reducing the cost of care or being cost neutral. This will be more and more in favor of reducing cost as the price of cWGS continues to decrease. In geographies where specialists are limited, and clinical resources are sparse, it is imperative to create equitable access to genomic medicine and, in doing so, leapfrog these populations into next-generation care. Without attention paid to the problem of millions of undiagnosed individuals burdened by the diagnostic odyssey, genetic disease will become the primary cause of mortality in children in under-resourced areas in less than a decade (Holmes et al., 2010). Genetic Alliance's iHope Genetic Health programs will substantially address inherited disease in LMICs with excellent outcomes for the undiagnosed.