Altered α subunits in Tay-Sachs disease

SANDHOFF-JATZKEWITZ disease (type O variant), in which both hexosaminidase (Hex) A and B are deficient, has been shown to result from a mutation in the structural gene for subunit (β) common to both Hex A and B (refs 1, 2). This conclusion was based on the demonstration of the presence of enzymatically inactive protein (crossreacting material, CRM) in the liver samples of patients with Sandhoff disease (SD). In Tay-Sachs disease (TSD), in which only Hex A is deficient, CRM was not demonstrated previously, using antiserum raised against native Hex A and B (refs 2-4). It was, however, suggested that this disorder is also due to a mutation in the structural gene coding for the unique sub-unit (α) of Hex A (refs 1, 2). Using antisera raised against cross-linked human placental Hex A, we have demonstrated and report here the presence of CRM in liver samples from eight unrelated patients with TSD.