Molecular Genetics & Genomic Medicine (Apr 2024)

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

  • Kanako Higashi,
  • Yuri Sonoda,
  • Noriyuki Kaku,
  • Fumihiko Fujii,
  • Fumiya Yamashita,
  • Sooyoung Lee,
  • Vlad Tocan,
  • Go Ebihara,
  • Wakato Matsuoka,
  • Kenichi Tetsuhara,
  • Motoshi Sonoda,
  • Pin Fee Chong,
  • Yuichi Mushimoto,
  • Kanako Kojima‐Ishii,
  • Masataka Ishimura,
  • Yuhki Koga,
  • Atsuhisa Fukuta,
  • Nana Akagi Tsuchihashi,
  • Yoshikazu Kikuchi,
  • Takahito Karashima,
  • Takaaki Sawada,
  • Taeko Hotta,
  • Makoto Yoshimitsu,
  • Hideyuki Terazono,
  • Tatsuro Tajiri,
  • Takashi Nakagawa,
  • Yasunari Sakai,
  • Kimitoshi Nakamura,
  • Shouichi Ohga

DOI
https://doi.org/10.1002/mgg3.2427
Journal volume & issue
Vol. 12, no. 4
pp. n/a – n/a

Abstract

Read online

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.

Keywords