ABSTRACT
The clinical phenotype of Sandhoff disease may be indistinguishable from that of Tay-Sachs disease (Chapter 91), but there may be hepatosplenomegaly in Sandhoff disease. The distinction between the two conditions was delineated by Sandhoff et al. [1] in 1968 in a patient who was unusual in that he stored ganglioside not only in the brain but also in other viscera. In contrast to patients with Tay-Sachs disease, the activity of total hexosaminidase was found to be deficient [1]. Hexosaminidase B is a glycoprotein homopolymer with four identical subunits; its structure is designated 22 [2,3]. Hexosaminidase A is a heteropolymer of and subunits. Activity of the Hex-A and Hex-B isozymes are defective because of a defective subunit. The disease has also been referred to as GM2 gangliosidosis (variant O). The Hex-B gene is located on chromosome 5q13 [4]. Heterogeneity has been observed in the mutations in the gene for Hex-B [5]. Most mutations lead to the most severe infantile onset phenotype. The causative mutations in these patients tend to be deletions, nonsense mutations, or splice site mutations. The most common is a 16 kb deletion that includes the promoter, exons 1 to 5 and part of the intron [6].
