At the beginning of the twentieth century, Dr. Archibald Garrod raised the issue of the chemical identity of man, and the continuation of this discussion eventually led to the issue of Inborn Error of Metabolism [1]. According to Garrod, each individual possesses a distinct chemical identity that sets them apart from others. Subsequently, scientists like Biddle and Tatum proposed the influential hypothesis of “one gene—one enzyme.” This hypothesis postulated that all the enzymes and proteins in the body are derived from a single gene. While the broad applicability of this theory is acknowledged today, there are variations in specific details, such as certain genes being responsible for producing multiple enzymes or proteins, and some enzymes being the outcome of the combined activity of several genes [2]. Additionally, Archibald Garrod’s discovery of Alkaptonuria at the beginning of the twentieth century played a pivotal role in shaping the concept of metabolic diseases [3]. Alkaptonuria is characterized by the absence of a functional gene copy that produces the enzyme responsible for breaking down a substance called homogentisic acid, which is typically present in human urine. Consequently, individuals with Alkaptonuria are unable to metabolize this substance, leading to its accumulation in the urine. Exposure to sunlight causes the urine to darken, turning it black. Alkaptonuria disease exemplifies the fundamental principles of metabolic diseases [4] that we are going to discuss their genetic causes and new approaches toward these disorders in this chapter.