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

Autor: Higashi K; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.; Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan., Sonoda Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Kaku N; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.; Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan., Fujii F; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Yamashita F; Department of Pediatrics, National Hospital Organization Fukuoka Higashi Medical Center, Koga, Japan., Lee S; Department of Pediatrics, National Hospital Organization Fukuoka Higashi Medical Center, Koga, Japan., Tocan V; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Ebihara G; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Matsuoka W; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.; Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan., Tetsuhara K; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.; Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan., Sonoda M; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Chong PF; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Mushimoto Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Kojima-Ishii K; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Ishimura M; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Koga Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Fukuta A; Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Tsuchihashi NA; Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Kikuchi Y; Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Karashima T; Department of Clinical Chemistry and Laboratory of Medicine, Kyushu University Hospital, Fukuoka, Japan., Sawada T; Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Hotta T; Department of Clinical Chemistry and Laboratory of Medicine, Kyushu University Hospital, Fukuoka, Japan., Yoshimitsu M; Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan., Terazono H; Department of Clinical Pharmacy and Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Tajiri T; Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Nakagawa T; Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Sakai Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Nakamura K; Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Ohga S; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Apr; Vol. 12 (4), pp. e2427.
DOI: 10.1002/mgg3.2427
Abstrakt: 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.
(© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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