Next Generation of Assay: Diagnostic Dilemmas of Lysosomal Disorders

Introduction: Lysosomal disorders (LDs) are approximately 60 diseases and growing various inherited diseases that, although individually rare, significant when the group is considered as a whole. The estimated combined incidence of the LDs is variable from one case in every 4000 to 13,000 births across different studies, with recent data from newborn screening programs showing even higher incidence. Patients with LDs, can present with a constellation of nonspecific and / or overlapping symptoms and variable clinical signs. Establishing a correct diagnosis to reducing the diagnostic delay and missed cases, is a dilemmaMaterials & Methods: In recent years, the development of tandem mass spectrometry (MS/MS) technology has been considerably expanded even led to a major shift in the approach to newborn screening. Despite this choice, only one third of the classical LDs have a clinically available specific enzymatic test that can be used as a diagnostic test. In addition, there is a wide spectrum of LDs that result from defective function of non-enzymatic lysosomal proteins or non-lysosomal proteins involved in lysosomal biogenesis. While this situation brings diagnostic odyssey years before the correct diagnosis, the next generation of genetics assays paved the way to achieve definitive diagnoses of this group of diseases.Results: Application of NGS strategies for clinical diagnosis has significantly developed dealing with these issues and, also, has made any special change to the diagnostic workflow. NGS through a multi- characteristics has been placed in the first line of the clinical assay. A gradual, NGS platforms were subsequently emerged on the market entitled Direct To Consumer genetic test service with proud of its powerful for making diagnoses. Here, is where one must stop and consider the limitations and challenges of NGS, in addition to the nature of this group of disorders.Conclusion & discussion: Given that a precise and definitive diagnosis, requires NGS result in combination with appropriate genetic counseling, biochemical and clinical data, therefore, it seems formation a LDs Odyssey Committee (LDsOC), comprised of physician and professional genetician and biochemists can have a significant and very powerful role in making definitive and on time diagnoses, particularly in the challenging cases

کلیدواژه ها:

Lysosomal Disorders ، NGS ، MS/MS technology ، Direct To Consumer genetic test