Perspective: The rare must become common

Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives

“…However, this incidence may be underestimated since LDs are multisystem diseases and can be mis-diagnosed as other conditions affecting the same organs, and also acute cases may lead to patient death prior to diagnosis in countries/regions without an established screening system or with low medical awareness [58]. These reasons may also leave mild cases undiagnosed for decades, at which point the damage may be irreversible for treatment [58]. Therefore, several efforts are geared towards early diagnosis of LDs through implementation of population screening measures, such as newborn screening to detect the underlying genetic defect [58, 59].…”

“…These reasons may also leave mild cases undiagnosed for decades, at which point the damage may be irreversible for treatment [58]. Therefore, several efforts are geared towards early diagnosis of LDs through implementation of population screening measures, such as newborn screening to detect the underlying genetic defect [58, 59]. Because of their cost, these measures are often met with criticism regarding the utility of such programs when an effective therapeutic intervention does not exist [60].…”

“…Because of their cost, these measures are often met with criticism regarding the utility of such programs when an effective therapeutic intervention does not exist [60]. Furthermore, since the manifestation of the underlying genetic defect in LDs is variable, a positive screening test often leads to a lifelong monitoring of the patient even when they do not exhibit severe symptoms [58]. However, with the development of high-throughput analytical technologies and discovery of newer therapies that have demonstrated a benefit when started early, newborn screening programs for LDs (such as the case for Krabbe, MPS I, Pompe and Fabry diseases) are now implemented in several states in the U.S. [59, 60].…”

“…However, with the development of high-throughput analytical technologies and discovery of newer therapies that have demonstrated a benefit when started early, newborn screening programs for LDs (such as the case for Krabbe, MPS I, Pompe and Fabry diseases) are now implemented in several states in the U.S. [59, 60]. Another approach that has been implemented quite successfully is that of screening potential parent-carriers in families with disease history or among high prevalence subpopulations, which can help to prevent the spread of these diseases [58]. In fact, carrier screening approaches have reduced the incidence of Tay-Sach’s disease in the Ashkenazi Jewish population by 90% [58].…”

“…Another approach that has been implemented quite successfully is that of screening potential parent-carriers in families with disease history or among high prevalence subpopulations, which can help to prevent the spread of these diseases [58]. In fact, carrier screening approaches have reduced the incidence of Tay-Sach’s disease in the Ashkenazi Jewish population by 90% [58]. With the advances in whole genome sequencing technology, both in terms of throughput and cost, such measures may be successfully adapted in the future.…”