Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease

Gaucher Disease Type 3 (GD3) is a rare lysosomal storage disorder characterized by both visceral and neurological involvement. Pulmonary manifestations can significantly impact prognosis and quality of life. This case report highlights the challenges in managing severe pulmonary involvement in GD an...

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Main Authors: Vincenza Gragnaniello, Silvia Carraro, Tiziana Zangardi, Chiara Cazzorla, Daniela Gueraldi, Alberto B. Burlina
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pediatrics
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Online Access:https://www.frontiersin.org/articles/10.3389/fped.2025.1604433/full
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author Vincenza Gragnaniello
Vincenza Gragnaniello
Silvia Carraro
Tiziana Zangardi
Chiara Cazzorla
Daniela Gueraldi
Alberto B. Burlina
Alberto B. Burlina
author_facet Vincenza Gragnaniello
Vincenza Gragnaniello
Silvia Carraro
Tiziana Zangardi
Chiara Cazzorla
Daniela Gueraldi
Alberto B. Burlina
Alberto B. Burlina
author_sort Vincenza Gragnaniello
collection DOAJ
description Gaucher Disease Type 3 (GD3) is a rare lysosomal storage disorder characterized by both visceral and neurological involvement. Pulmonary manifestations can significantly impact prognosis and quality of life. This case report highlights the challenges in managing severe pulmonary involvement in GD and explores novel treatment approaches. We present a case of a patient with GD3, diagnosed through neonatal screening, who developed severe lung disease despite early initiation of enzyme replacement therapy (ERT). The patient, carrying compound heterozygous variants in the GBA1 gene (p.Leu483Pro, [p.His294Gln + p.Asp448His]), experienced respiratory distress requiring oxygen therapy from the age of 4 months. High-resolution computed tomography revealed a typical interstitial lung disease pattern. Despite ERT and a marked reduction in storage biomarkers, pulmonary symptoms persisted, accompanied by elevated inflammatory markers. We implemented a treatment regimen of systemic corticosteroids followed by hydroxychloroquine, resulting in clinical improvement. Furthermore, we observed a decrease in inflammatory biomarkers, such as TNF-alpha and Pp38 MAPK levels, providing insights into possible pathogenic mechanisms. This case underscores the limitations of ERT in addressing pulmonary manifestations of GD and highlights the need for personalized treatment strategies. It also emphasizes the importance of further research into the pathogenesis of pulmonary damage in Gaucher disease to develop more effective therapies for these challenging cases. The positive response to anti-inflammatory and immunomodulatory therapies suggests a potential role for these approaches in managing GD-related lung disease.
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spelling doaj-art-7d46b48a507249a695f53df932c4e3892025-08-20T03:10:02ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-06-011310.3389/fped.2025.16044331604433Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher diseaseVincenza Gragnaniello0Vincenza Gragnaniello1Silvia Carraro2Tiziana Zangardi3Chiara Cazzorla4Daniela Gueraldi5Alberto B. Burlina6Alberto B. Burlina7Division of Inherited Metabolic Diseases, Department of Women's and Children's Health, University of Padova, Padova, ItalyDivision of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padova, Padova, ItalyUnit of Pediatric Allergy and Respiratory Medicine, Women’s and Children’s Health Department, University of Padova, Padova, ItalyPediatric Emergency Department, Department for Women’s and Children’s Health, University of Padua, Padua, ItalyDivision of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padova, Padova, ItalyDivision of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padova, Padova, ItalyDivision of Inherited Metabolic Diseases, Department of Women's and Children's Health, University of Padova, Padova, ItalyDivision of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padova, Padova, ItalyGaucher Disease Type 3 (GD3) is a rare lysosomal storage disorder characterized by both visceral and neurological involvement. Pulmonary manifestations can significantly impact prognosis and quality of life. This case report highlights the challenges in managing severe pulmonary involvement in GD and explores novel treatment approaches. We present a case of a patient with GD3, diagnosed through neonatal screening, who developed severe lung disease despite early initiation of enzyme replacement therapy (ERT). The patient, carrying compound heterozygous variants in the GBA1 gene (p.Leu483Pro, [p.His294Gln + p.Asp448His]), experienced respiratory distress requiring oxygen therapy from the age of 4 months. High-resolution computed tomography revealed a typical interstitial lung disease pattern. Despite ERT and a marked reduction in storage biomarkers, pulmonary symptoms persisted, accompanied by elevated inflammatory markers. We implemented a treatment regimen of systemic corticosteroids followed by hydroxychloroquine, resulting in clinical improvement. Furthermore, we observed a decrease in inflammatory biomarkers, such as TNF-alpha and Pp38 MAPK levels, providing insights into possible pathogenic mechanisms. This case underscores the limitations of ERT in addressing pulmonary manifestations of GD and highlights the need for personalized treatment strategies. It also emphasizes the importance of further research into the pathogenesis of pulmonary damage in Gaucher disease to develop more effective therapies for these challenging cases. The positive response to anti-inflammatory and immunomodulatory therapies suggests a potential role for these approaches in managing GD-related lung disease.https://www.frontiersin.org/articles/10.3389/fped.2025.1604433/fullGaucher diseaseglucocerebrosidasenewborn screeninginterstitial lung diseasecorticosteroid therapyhydroxychloroquine
spellingShingle Vincenza Gragnaniello
Vincenza Gragnaniello
Silvia Carraro
Tiziana Zangardi
Chiara Cazzorla
Daniela Gueraldi
Alberto B. Burlina
Alberto B. Burlina
Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease
Frontiers in Pediatrics
Gaucher disease
glucocerebrosidase
newborn screening
interstitial lung disease
corticosteroid therapy
hydroxychloroquine
title Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease
title_full Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease
title_fullStr Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease
title_full_unstemmed Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease
title_short Case Report: Novel treatment approach for severe interstitial lung disease in type 3 Gaucher disease
title_sort case report novel treatment approach for severe interstitial lung disease in type 3 gaucher disease
topic Gaucher disease
glucocerebrosidase
newborn screening
interstitial lung disease
corticosteroid therapy
hydroxychloroquine
url https://www.frontiersin.org/articles/10.3389/fped.2025.1604433/full
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