Pulmonary involvement in selected lysosomal storage diseases and the impact of enzyme replacement therapy: A state ‐of‐the art review
AbstractLysosomal storage disorders (LSDs) are multisystemic, progressive, and clinically very heterogeneous. Respiratory complications are not regarded as the principal problems of LSDs, but significantly impact morbidity. In this review, we focus on pulmonary complications observed in late ‐onset LSDs, their milder forms that are recognized in adulthood. We also discuss the effects of enzyme replacement therapy (ERT) on the respiratory system in patients with particular LSDs. We searched the PubMed database, retrieving research papers on pulmonary complications of LSDs currently tre ated with ERT (the conditions are abbreviated GD3; NPDB; LOPD; MPS I, II, IVA, VI; and FD) and the effects of such treatment. Although some studies indicated that ERT was helpful in terms of reducing chest computed tomography abnormalities, infection frequency, and organomegaly, the data are not con clusive, and the mechanism of action of ERT in the respiratory system remains unclear for some LSDs including late‐onset Pompe disease and Gaucher disease type III. The optimal timing of treatment for pre‐symptomatic or symptomatic patients, treatment duration, and whether such treatment modulat es inflammation (as has been suggested in patients with Fabry disease), remain to be explored.
Publication date: Available online 24 February 2020Source: Blood Cells, Molecules, and DiseasesAuthor(s): David J. Kuter, Michael Wajnrajch, Betina Hernandez, Rong Wang, Raul Chertkoff, Ari Zimran
To assess magnetic resonance spectroscopy (MRS) bone marrow fat fractions' ability to discern between untreated Gaucher disease patients and healthy controls based on assessment of bone marrow infiltration and evaluate response to enzyme replacement therapy (ERT) on serial imaging.
y Levade Nathalie Andrieu-Abadie The roles of ceramide and its catabolites, i.e., sphingosine and sphingosine 1-phosphate, in the development of malignancies and the response to anticancer regimens have been extensively described. Moreover, an abundant literature points to the effects of glucosylceramide synthase, the mammalian enzyme that converts ceramide to β-glucosylceramide, in protecting tumor cells from chemotherapy. Much less is known about the contribution of β-glucosylceramide and its breakdown products in cancer progression. In this chapter, we first review published and personal clinical...
Gaucher disease (GD), a rare lysosomal storage disorder caused by deficient glucocerebrosidase activity and consequent accumulation of glycosphingolipids in the mononuclear phagocyte system, may progress to disabling and potentially life-threatening complications when left undiagnosed and untreated. Unfortunately, because of non-specific signs and symptoms and lack of awareness, patients with type 1 GD, the most common non-neuropathic variant, frequently experience diagnostic delays. Since splenomegaly and thrombocytopenia are the dominant clinical features in many GD patients leading to first medical contact, the hepatolo...
Publication date: Available online 5 February 2020Source: Molecular Genetics and MetabolismAuthor(s): Shiny Nair, Noffar Bar, Mina L. Xu, Madhav Dhodapkar, Pramod K. MistryAbstractIn Gaucher disease type 1 (GD1), genetic deficiency of lysosomal glucocerebrosidase results in the accumulation of glucosylceramide and glucosylsphingosine (GlcSph), that underlie chronic lipid-mediated metabolic inflammation. An important age-related phenotype is high risk of monoclonal gammopathy (MG), including multiple myeloma. We identified GlcSph, a pathological lyso-sphingolipid exclusively elevated in GD, as a mediator of B cell activatio...
Publication date: February 2020Source: Molecular Genetics and Metabolism, Volume 129, Issue 2Author(s): Ana C. Vásquez Salazar, Alfredo Uribe Ardila
Publication date: February 2020Source: Molecular Genetics and Metabolism, Volume 129, Issue 2Author(s): Chanan Stauffer, Margo S. Breilyn, Manisha Balwani
Publication date: February 2020Source: Molecular Genetics and Metabolism, Volume 129, Issue 2Author(s): Rodrigo T. Starosta, Marina Siebert, Ida Vanessa D. Schwartz, Carlos Thadeu S. Cerski
Publication date: February 2020Source: Molecular Genetics and Metabolism, Volume 129, Issue 2Author(s): Pankaj Sharma, Shruthi Santhanakrishnan, Alta Steward, Barbara Stubblefield, Grisel Lopez, Nahid Tayebi, Ellen Sidransky
Publication date: February 2020Source: Molecular Genetics and Metabolism, Volume 129, Issue 2Author(s): Christine Serratrice, Jérôme Stirnemann, Amina Berrahal, Nadia Belmatoug, Fabrice Camou, Thierry Billette de Villemeur, Florence Dalbies, Bérangère Cador, Agathe Masseau, Anaïs Brassier, Bénédicte Hivert, Laure Swiader, Ivan Bertchansky, Claire de Moreuil, Brigitte Chabrol, Isabelle Durieu, Vanessa Leguy-Seguin, Leonardo Astudillo, Sébastien Humbert, Samia Pichard