Sandhoff Disease (HEXB)

Sandhoff disease is an autosomal recessive disorder resulting from pathogenic variants in the HEXB gene. It has been reported in individuals from different ethnicities, but there is an increased prevalence of the disease in specific isolated groups, including the Metis of Northern Saskatchewan and Argentinian Creoles. Pathogenic HEXB variants result in loss of function of the hexosaminidase B enzyme, causing accumulation of GM2 gangliosides in body tissues. Several different forms of the disease exist, including the infantile and later-onset variants. The infantile form, which is the most common, has an onset of symptoms around 6 months of age. Clinical features include progressive loss of coordination, seizures, difficulty swallowing and poor pulmonary function. Affected individuals eventually become blind, severely intellectually disabled, paralyzed and unaware of their surroundings. Death usually occurs at 3 to 5 years of age. The juvenile form usually has an age of onset between 2 and 10 years. The progression of the disease is similar to that of the infantile form, and death occurs between 4 and 25 years of age. In the chronic form, age of onset is similar to that of the juvenile form, but the symptoms progress more slowly. The clinical presentation is one of ataxia and dystonia. Survival is long-term. The adult-onset form is characterized by progressive muscle loss, weakness and difficulty speaking. Age of onset, symptoms and severity are variable among individuals. Survival is long-term. A genotype-phenotype correlation has been observed, where the presence of one allele with residual enzyme activity is likely to result in a later-onset phenotype. However, it may not be possible to predict the age of onset in all patients.

For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.