Substrate deprivation
therapy has been successfully applied in a number of
lysosomal storage diseases, such as
Gaucher disease. So far only limited experience is available in
Sandhoff disease. We initiated substrate deprivation
therapy in one male patient, who initially presented at the age of 3.5 years with
epilepsy and regression in motor skills and speech development.
Juvenile Sandhoff disease was diagnosed on the basis of a decreased
hexosaminidase activity in leukocytes and a homozygous HEXB gene mutation. After the
epilepsy was controlled, the
clinical course remained stable for years, defined by a mild proximal
myopathy and stable
mental retardation. At 14 years of age the patient experienced a second episode with progressively worsening general condition with diminishing muscle power and progressive
ataxia. Treatment was started with the N-alkylated imino
sugar miglustat, inhibiting the
glucosylceramide synthase, an essential
enzyme for the synthesis of
glycosphingolipids. Diarrhoea was treated with
lactose restriction. We performed detailed biochemical investigations, motor and mental development analysis, brain imaging, organ function studies and quality of life score prior to and at different time points after start of the treatment. Two years after the initiation of
therapy the patient has a stable neurological picture without further regression in his motor development,
ataxia or intelligence. There is a subjective improvement in the fine motor skills and walking up the stairs but no change in the quality of life score. Under treatment with
miglustat the
clinical course in our patient with
Sandhoff disease did not further deteriorate.