{Reference Type}: Review
{Title}: Rapid and long-lasting efficacy of high-dose ambroxol therapy for neuronopathic Gaucher disease: A case report and literature review.
{Author}: Higashi K;Sonoda Y;Kaku N;Fujii F;Yamashita F;Lee S;Tocan V;Ebihara G;Matsuoka W;Tetsuhara K;Sonoda M;Chong PF;Mushimoto Y;Kojima-Ishii K;Ishimura M;Koga Y;Fukuta A;Tsuchihashi NA;Kikuchi Y;Karashima T;Sawada T;Hotta T;Yoshimitsu M;Terazono H;Tajiri T;Nakagawa T;Sakai Y;Nakamura K;Ohga S;
{Journal}: Mol Genet Genomic Med
{Volume}: 12
{Issue}: 4
{Year}: 2024 Apr
{Factor}: 2.473
{DOI}: 10.1002/mgg3.2427
{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.