GM1 gangliosidosis – therapeutical trial with Miglustat (Zavesca®) – a case report

This case report presents an infant which was diagnosed with GM1-Gangliosidosis at the age of 4 months. Miglustat therapy was initiated at the age of 7 months. The principle of the therapy is a substrate reduction therapy which is indicated for the lysosomalstorage disorder Morbus Gaucher type 1. Initial symptoms at the time of diagnosis respectively start of therapy were: hepatosplenomegaly, muscular hypotonia, fast proceeding pneumopathy. MRI-changes of the neurocranium showed a temporary marked brain atrophy. Subtle hints of development retardation were given at the beginning of therapy. Laboratory: the diagnosis was based on lymphocyte-vakuoles count and the presence of oligosaccharides in the urine. The activity of beta-galactosidase amounted to 3.0µmol/g.h. (norm 100–400) in the leucocytes. Miglustat therapy was increased stepwise to a dosage of 100mg/day (12.5mg/kg/day, 100mg/0. 47 m²/day) p.o. in three single dosages. No clinical nor chemical side-effects were seen during slow increase of dosage. After the dosage of 70mg/day a stagnation and in the course a decrease of the size of spleen and liver was noticed. Because of the stagnation of psychomotoric development at the age of 10 months, the end target dosage was increased to 150–200mg/day. The presentation will include the neurological findings as well as the course of organe size of liver and spleen, skeleton changes and chronic pneumopathy and the change in laboratory parameters during Miglustat therapy (following recommendation of a standard protocol). Ethical considerations of therapy decision should also be discussed for the unfavourable prognosis for the diagnosis of infantile GM1-Gangliosidosis.

Keywords: GM1-gangliosidosis, therapy, infantile, miglustat