Rapid and long-lasting efficacy of high-dose ambroxol therapy for neuronopathic Gaucher disease : A case report and literature review
© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Molecular genetics & genomic medicine - 12(2024), 4 vom: 30. Apr., Seite e2427 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Higashi, Kanako [VerfasserIn] |
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| Links: |
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| Themen: |
200168S0CL |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 01.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/mgg3.2427 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Higashi, Kanako |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Rapid and long-lasting efficacy of high-dose ambroxol therapy for neuronopathic Gaucher disease |b A case report and literature review |
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| 520 | |a © 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Tocan, Vlad |e verfasserin |4 aut | |
| 700 | 1 | |a Ebihara, Go |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuoka, Wakato |e verfasserin |4 aut | |
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