Rapid and long‐lasting efficacy of high‐dose ambroxol therapy for neuronopathic Gaucher disease: A case report and literature review

Abstract Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1‐encoded enzyme, β‐glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High‐dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long‐term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long‐lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high‐dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long‐lasting effect of ambroxol‐based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.