Ambroxol as adjunctive therapy for neurologic symptoms in Gaucher disease type 3: Case report.

Background: Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase (GC) deficiency, with type 3 always having a neurological impairment. We describe a case of a patient with GD type 3 receiving enzyme replacement therapy (ERT) and ambroxol as adjunctive therapy for seizures and myoclonus/ataxia.

Case report: A 10-year-old male presents at 12 months of age for failure to thrive, splenomegaly, developmental delay, oculomotor apraxia, ataxia, and myoclonic epilepsy. EEG showed myoclonic seizures, so antiepileptic drugs (AED) were instaurated. An elevated Chitotriosidase, low GC enzyme activity, and a sequence analysis on the GBA gene showing variants: c. 709A>G; p. Lys237Glu and c. 1448T>C; p. Leu483Pro, both heterozygous pathogenic and variant c-203A>G in 5 UTR heterozygous, confirmed GD type 3. At 18 months, the patient was put on Imiglucerase at 120 IU/kg every two weeks. Despite an optimal control of systemic features, epilepsy turned out refractory, coexisting with non-epileptic myoclonus. Miglustat was not tolerated; ambroxol was added in doses up to 12 mg/kg/day. After several weeks, there was a perceptible clinical improvement in daily myoclonus and focal seizures. Ataxia has been stable, despite the previous progression.

Discussion: Therapeutic alternatives in managing neurologic symptoms of neuronopathic GD, other than AED, must be improved. Ambroxol has been suggested as a pharmacological chaperone therapy in this group of patients, showing, in small series, improvement in neurological symptoms such as myoclonus and seizures, which we could replicate in our case. Besides this effect, we recorded the stabilization of the ataxia shown in our patient.

Conclusions: Adjunctive ambroxol usage might improve neurologic GD type 3 symptoms.