GM(2)-gangliosidosis is a rare and heterogeneous inherited metabolic disorder caused by autosomal recessive mutations in genes encoding the lysosomal
enzyme β-
hexosaminidase, resulting in the accumulation of
ganglioside GM(2) in various tissues, particularly the central nervous system. It is characterized by progressive neurological deterioration that mainly affects motor and spinocerebellar function. Several forms of GM(2)-gangliosidosis exist, including the Sandhoff variant. Currently there is no treatment for these conditions, except for
palliative care.
Miglustat (
Zavesca) is a reversible inhibitor of
glucosylceramide synthase, which catalyses the first committed step in the synthesis of
glucose-based
glycolipids.
Miglustat has pharmacokinetic properties that allow it to cross the blood-brain barrier, and preclinical data suggest that it may benefit neuronopathic
lysosomal storage diseases. Here we present a case report of a Norwegian patient with
Sandhoff disease treated with
miglustat at our centre in Norway. The patient initially presented with
ataxia and
dysarthria at 2-3 years of age, which progressed slowly during childhood. At age 14, he experienced episodes of depression and apathy, leading to
weight loss. He was diagnosed with
Sandhoff disease at age 16. Following 2.5 years of treatment with
miglustat, his
body weight was stabilized and
disease progression appeared to have slowed, as evidenced by the lack of progressive brain
atrophy. His depressive symptoms were managed using electroconvulsive treatment (ECT), which improved general functioning. These findings suggest that
miglustat may provide beneficial effects in patients with
juvenile Sandhoff disease, and that ECT may alleviate depressive symptoms.