The Concept of Treatment in Lysosomal Storage Diseases

Even though sporadic reports of individual patients who were later classified having a lysosomal storage disease began to appear toward the end of the 19th century (Tay, 1881; Gaucher, 1882; Sachs, 1887), little was known about the true nature of storage materials in the LSDs until the early third of the 20th century. In 1907, F. Marchand reported that a hyaline-like material was stored in the “so-called idiopathic splenomegaly” of the Gaucher type. However, he erroneously believed that it was not a lipid because the material did not react with osmic acid. The accumulating substance was identified as a cerebroside by Lieb in 1924. Cerebrosides consist of three components: two are lipids (sphingosine and fatty acid), and the third is a carbohydrate. Galactocerebroside had been known since the beginning of this century to be the preponderant lipid of the brain on a weight basis. Lieb believed that this cerebroside accumulated in the organs and tissues of patients with Gaucher disease. However, the optical rotation of an aqueous solution of the sugar derived from the accumulating cerebroside was incompatible with its being galactose. In 1934, Aghion reported that the sugar moiety of the accumulating cerebroside was glucose rather than galactose. This finding was confirmed by many investigators, thereby conclusively establishing that the principal accumulating lipid in patients with Gaucher disease is glucocerebroside.