7. Discovery of β-hexosaminidase a deficiency in Tay-Sachs disease

Abstract

In this chapter, the discovery of β-Hexosaminidase, a deficiency in Tay-Sachs disease (TSD) is discussed. This chapter discusses the thoughts of Shintaro Okada and John S. O’Brien, and recollections about how they discovered the deficiency of hexosaminidase A in TSD nearly 30 years ago. There are five levels of sophistication in understanding the molecular basis of a hereditary disease such as TSD. The first level is the description of the phenotype, including the clinical features, progression, and pathology of the disease. The second level is determination of the mode of genetic transmission. The third level is the discovery of the biochemical defect responsible for the pathophysiology of the disorder. The fourth level is the elucidation of the enzyme, catalytic or structural protein defect that underlies the biochemical defect, and the fifth level is the definition of the genetic defect at the nucleic acid level.