Respiratory impairment in Niemann-Pick B disease: Two case reports and review for the pulmonologist

Capron, Thibaut; Trigui, Y.; Gautier, C; Puech, Basile; Chanez, Pascal; Reynaud‐Gaubert, Martine

doi:10.1016/j.resmer.2019.05.001

Cited by 8 publications

(11 citation statements)

References 30 publications

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“…Histological features of murine NPC1-caused lung disease are shown in Figure 4A–C. Many patients suffer from incurable bacterial or viral bronchopulmonary infections that are exacerbated by NPC1-predamaged pulmonary tissue [101].…”

Section: Pathology Of Npc1 In Humans and Micementioning

confidence: 99%

Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1

Bräuer

Kuhla

Holzmann

et al. 2019

IJMS

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Rare diseases are a heterogeneous group of very different clinical syndromes. Their most common causes are defects in the hereditary material, and they can therefore be passed on to descendants. Rare diseases become manifest in almost all organs and often have a systemic expressivity, i.e., they affect several organs simultaneously. An effective causal therapy is often not available and can only be developed when the underlying causes of the disease are understood. In this review, we focus on Niemann–Pick disease type C1 (NPC1), which is a rare lipid-storage disorder. Lipids, in particular phospholipids, are a major component of the cell membrane and play important roles in cellular functions, such as extracellular receptor signaling, intracellular second messengers and cellular pressure regulation. An excessive storage of fats, as seen in NPC1, can cause permanent damage to cells and tissues in the brain and peripheral nervous system, but also in other parts of the body. Here, we summarize the impact of NPC1 pathology on several organ systems, as revealed in experimental animal models and humans, and give an overview of current available treatment options.

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Section: Pathology Of Npc1 In Humans and Micementioning

confidence: 99%

Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1

Bräuer

Kuhla

Holzmann

et al. 2019

IJMS

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“…In the presence of ILD of unknown cause, bronchoscopy with bronchoalveolar lavage can be very helpful as it confirms the lung involvement and, in the presence of other findings suggestive of NPD (such as enzyme testing, gene sequencing and biomarkers), can avoid a lung biopsy [1,3,7]. In this disease, the bronchoalveolar lavage typically shows increased cell numbers and large multivacuolated histiocytes containing granules stained deep blue with May-Grunwald-Giemsa stain (Niemann-Pick cells) [1,5].…”

Section: Discussionmentioning

confidence: 99%

“…Neurological symptoms appear as psychomotor retardation and even rapid regression of developmental milestones. These children usually do not survive past three years often due to respiratory failure [4,5]. NPD type C can present at any age but usually during childhood and affected individuals can have visceral, neurological and psychiatric manifestations mainly: ataxia, dystonia, supranuclear gaze palsy, dysphagia, progressive cognitive decline and severe liver and lung disease [2,6].…”

Section: Introductionmentioning

confidence: 99%

“…The most common presentations are hepatosplenomegaly, interstitial lung disease (ILD) causing recurrent lung infections, haematological manifestations with thrombocytopenia and leukopenia, slowed bone growth and even decreased bone mineral density [3]. Typical NPD type B do not exhibit neurological manifestations but a subset of these patients may have variable degrees of peripheral neurological symptoms [5]. Respiratory involvement occurs in all three types of NPD but most frequently in type B and tends to be the major cause of mortality and morbidity in these patients [3,4,7].…”

Section: Introductionmentioning

confidence: 99%

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Niemann-Pick Type B: A Rare Cause of Interstitial Lung Disease

Martins¹,

Rocha²,

Guimas³

et al. 2022

Cureus

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Niemann-Pick disease (NPD) is a rare lysosomal storage disease (LSD) with multisystemic involvement. The disease is heterogeneous and classified into three subtypes: type A and B result from deficient acid sphingomyelinase activity and leads to the accumulation of sphingomyelin and type C is a genetically different disease resulting from defective intracellular trafficking of cholesterol with accumulation of glycosphingolipids. Type A is generally a neurodegenerative disease and is fatal in infancy. Type B is a less severe form characterized by pulmonary involvement, hepatosplenomegaly, hyperlipidemia and most patients live into adulthood. In type C, clinical presentation is dominated with neurological involvement. Pulmonary involvement occurs in all three types of Niemann-Pick but most frequently in type B. Clinical manifestations range from a lack of symptoms to respiratory failure, and respiratory symptoms are usually mild with recurrent cough, dyspnoea on exertion and recurrent respiratory infections. Interstitial lung disease (ILD) is the most prominent feature with slow progression, characterized by worsening pulmonary function tests. In recent years, enzyme replacement therapy has shown promising results in clinical trials, such as improvement in organomegaly and pulmonary involvement with the potential to improve patients' lives. We present three cases of NPD with pulmonary involvement, each exhibiting a different pattern of ILD and evaluate therapeutic options.

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“…Pulmonary involvement, mainly ILD, occurs in all three types of ASMD but most frequently in type B. ILD may be diagnosed in newborns to adults in their late 40s, may precede ASMD diagnosis or may develop during follow-up [55,56]. Up to 42% of patients report shortness of breath at ASMD diagnosis [46].…”

Section: Pulmonary Manifestationsmentioning

confidence: 99%

Interstitial lung disease in lysosomal storage disorders

et al. 2021

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Lysosomes are intracellular organelles that are responsible for degrading and recycling macromolecules. Lysosomal storage diseases (LSDs) are a group of inherited diseases caused by mutations affecting genes that encode the function of the lysosomal enzymes. Three LSDs are associated with lung involvement and/or interstitial lung disease (ILD): Gaucher disease (GD); Niemann–Pick disease, also known as acid sphingomyelinase deficiency (ASMD); and Fabry disease (FD). In GD and in ASMD, analysis of bronchoalveolar lavage fluid and lung biopsy can be informative, showing foamy cells. In GD, ILD is rare. Enzyme replacement therapy (ERT) has been available since 1991 and has greatly changed the natural history of GD, with pulmonary failure and death reported before the ERT era. In ASMD, ILD is frequent and is usually associated with spleen enlargement, low platelet cell count and low level of high-density lipoprotein-cholesterol. Results of ERT are promising regarding preliminary results of olipudase alfa in paediatric and adult ASMD populations. The most frequent respiratory manifestation in FD is COPD-like symptoms regardless of smoking habit and dyspnoea due to congestive heart failure. Early diagnosis of these three LSDs is crucial to prevent irreversible organ damage. Early initiation of ERT can, at least in part, prevent organ failure.

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Respiratory impairment in Niemann-Pick B disease: Two case reports and review for the pulmonologist

Cited by 8 publications

References 30 publications

Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1

Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1

Niemann-Pick Type B: A Rare Cause of Interstitial Lung Disease

Interstitial lung disease in lysosomal storage disorders

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