Pulmonary manifestations in Niemann-Pick type C disease with mutations in NPC2 gene: case report and review of literature

Sheth, Jayesh; Joseph, Jijo John; Shah, Krati; Muranjan, Mamta; Mistri, Mehul; Sheth, Frenny

doi:10.1186/s12881-017-0367-x

Cited by 22 publications

(13 citation statements)

References 22 publications

(22 reference statements)

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“…Similarly, Guillemot et al reported a high rate of ILD in Niemann‐Pick disease. Few case reports describe PAP in Niemann‐Pick disease . As compatible with the literature, our patients showed typical respiratory manifestations such as chronic airway aspirations, recurrent pneumonia, ILD, and PAP.…”

Section: Discussionsupporting

confidence: 88%

“…ILD may be observed in lysosomal storage disorders (LSD) and lysinuric protein intolerance . Immune defects, such as neutropenia or lymphocyte function impairment, may occur in hereditary orotic aciduria and glycogenosis type 1 and 2 and increase susceptibility to lower respiratory tract infections (LTRI) .…”

Section: Introductionmentioning

confidence: 99%

“…ILD may be observed in lysosomal storage disorders (LSD) and lysinuric protein intolerance. [8][9][10] Immune defects, such as neutropenia or lymphocyte function impairment, may occur in hereditary orotic aciduria and glycogenosis type 1 and 2 and increase susceptibility to lower respiratory tract infections (LTRI). 4,5 Several IMD, glycogenosis and LSDs, such as mucopolysaccharidoses (MPS), may lead to alveolar hypoventilation by causing respiratory muscle weakness, disruption of respiratory mechanics and/or chest or spine deformities.…”

Section: Introductionmentioning

confidence: 99%

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Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

İlarslan

Günay

Çobanoğlu

et al. 2019

Pediatric Pulmonology

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Objectives We aimed to call attention to respiratory system manifestations which occur in the course of many inherited metabolic diseases (IMD), and present as the leading cause of death. Materials and Methods We retrospectively reviewed the diagnosis, treatment, and outcome of patients evaluated at our hospital between June 2012 and June 2018 with a diagnosis of IMD and accompanying respiratory manifestations. Results A total of 50 children (29 [58%] male, 21 [42%] female) with IMD and respiratory manifestations were defined. Disorders of intracellular metabolism (n = 33, 66%) formed the majority, followed by intoxication type metabolic disorders (n = 9, 18%) and energy metabolism disorders (n = 8, 16%). The most frequent respiratory symptoms were snoring (20, 40%), tachypnea (16, 32%) and wheezing (14, 28%). Physical examination findings were signs of respiratory distress (n = 28, 56%), crackles (n = 24, 48%), thoracic deformity (n = 23, 46%), decreased breath sounds (n = 17, 34%), rhonchus (n = 17, 34%), wheezing (n = 17, 34%) and stridor (n = 10, 20%). Major respiratory manifestations were chronic airway aspiration (n = 23, 46%), upper airway obstruction (n = 23, 46%), and recurrent pneumonia (n = 18, 36%). Twenty‐three 23 patients (46%) experienced endotracheal intubation, 9 patients (18%) required whole‐house mechanical ventilation and tonsilloadenoidectomy was performed in 7 patients (14%). Overall survival rate was 70% (n = 35) in a median follow‐up period of 2.36 (0.05‐5.86) years. Conclusions Respiratory system manifestations of IMD strongly relate with increased morbidity and mortality. Therefore, prompt diagnosis and correct intervention of respiratory complications with a multidisciplinary team including pediatric metabolic diseases specialists, pulmonologists, otorhinolaryngologists, physiotherapists, and anesthesiologists are crucial to prevent progression and irreversible damage.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

İlarslan

Günay

Çobanoğlu

et al. 2019

Pediatric Pulmonology

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“…Lipoproteinosis causes severe lung pathology in several other LSDs, such as Gaucher disease and Niemann-Pick disease types B, C1, and C2 (19,46,(51)(52)(53). Corresponding mouse models have been instrumental in characterizing disease progression (10,12,26).…”

Section: Introductionmentioning

confidence: 99%

Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency

Islam

Sikora

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Mice homozygous ( Asah1) for an orthologous patient mutation in Asah1 recapitulate human FD. In this study, we show significant impairment in lung function, including low compliance and increased airway resistance in a mouse model of ACDase deficiency. Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation and increased red blood cell production. Inflammatory cells were recruited to both perivascular and peribronchial areas of the lung. We observed large vacuolated foamy histiocytes that were full of storage material. An increase in vascular permeability led to protein leakage, edema, and impacted surfactant homeostasis in the lungs of Asah1 mice. Bronchial alveolar lavage fluid (BALF) extraction and analysis revealed accumulation of a highly turbid lipoprotein-like substance that was composed in part of surfactants, phospholipids, and ceramides. The phospholipid composition of BALF from Asah1 mice was severely altered, with an increase in both phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found at significantly higher levels in both BALF and lung tissue from Asah1 mice when compared with levels from wild-type animals. We demonstrate that a deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic lung injury caused by significant inflammation, and increased vascular permeability, leading to impaired lung function.

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“…Type a is dueto mutations in SPMD1 (11p15.4)and type b is due to mutations in SMPD2 (6q21). Type cis due to mutations in one of two genes, NPC1 (18q11.2, 95%) or NPC2 (14q24.3, 5%) [ 48 , 49 ]. There are varying degrees of hepatosplenomegaly, and neurological and pulmonary disease, this last predominantly in NPC2 mutations.…”

Section: Aetiologymentioning

confidence: 99%

Pulmonary alveolar proteinosis in children

Bush

Pabary

2020

Breathe

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Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. There is outlining of the secondary pulmonary lobules on the background of ground-glass shadowing and pathologically, filling of the alveolar spaces with normal or abnormal surfactant. PAP is rare and the common causes in children are very different from those seen in adults; autoimmune PAP is rare and macrophage blockade not described in children. There are many genetic causes of PAP, the best known of which are mutations in the genes encoding surfactant protein (SP)-B, SP-C, thyroid transcription factor 1, ATP-binding cassette protein 3, and the granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor α- and β- chains. PAP may also be a manifestation of rheumatological and metabolic disease, congenital immunodeficiency, and haematological malignancy. Precise diagnosis of the underlying cause is essential in planning treatment, as well as for genetic counselling. The evidence base for treatment is poor. Some forms of PAP respond well to whole-lung lavage, and autoimmune PAP, which is much commoner in adults, responds to inhaled or subcutaneous GM-CSF. Emerging therapies based on studies in murine models of PAP include stem-cell transplantation for GM-CSF receptor mutations.Educational aimsTo understand when to suspect that a child has pulmonary alveolar proteinosis (PAP) and how to confirm that this is the cause of the presentation.To show that PAP is an umbrella term for conditions characterised by alveolar filling by normal or abnormal surfactant, and that this term is the start, not the end, of the diagnostic journey.To review the developmental differences in the spectrum of conditions that may cause PAP, and specifically to understand the differences between causes in adults and children.To discuss when to treat PAP with whole-lung lavage and/or granulocyte–macrophage colony-stimulating factor, and review potential promising new therapies.

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Pulmonary manifestations in Niemann-Pick type C disease with mutations in NPC2 gene: case report and review of literature

Cited by 22 publications

References 22 publications

Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency

Pulmonary alveolar proteinosis in children

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