Gaucher disease
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Gaucher disease is the most common of the lysosomal storage diseases. Recognition of Gaucher disease as a reticuloendothelial storage disease was as early as 1907 and, in 1924, the stored material was identified as lipid and characterized as a cerebroside. Thrombocytopenia is a common hematologic manifestation of Gaucher disease. It may be accompanied by leukopenia and anemia, the full picture of hypersplenism, and resolves with splenectomy. Growth and development may be altered drastically in Gaucher disease. The perinatal lethal disease has often been considered a subtype of infants with type 2 Gaucher disease in infants with a rapid fulminant neonatal onset course. Gaucher disease is inherited in an autosomal recessive fashion. Some correlations of phenotype with genotype have emerged from increasing information on the nature of mutation in Gaucher disease. Among the earliest approaches to provide a source of active enzyme in Gaucher disease was the use of bone marrow transplantation.
Osteonecrosis and osteochondritis
Ashley W. Blom, David Warwick, Michael R. Whitehouse in Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Osteonecrosis appears as a distinctive feature in a number of non-traumatic disorders: joint infection, Perthes' disease, caisson disease, Gaucher's disease, systemic lupus erythematosus (SLE), high-dosage corticosteroid administration and alcohol abuse. Various mechanisms leading to capillary thrombosis have been demonstrated in patients with non-traumatic osteonecrosis. Computed tomography (CT) involves considerable radiation exposure and it is not very useful for diagnosing osteonecrosis. Where risk factors for osteonecrosis are recognized, preventive steps can be taken especially in the management of corticosteroid medication and alcohol abuse. 'Spontaneous' osteonecrosis of the knee is similar to osteochondritis dissecans of the medial femoral condyle, but it is distinguished by three important features: it appears in elderly people who are osteoporotic and the lesion invariably appears on the highest part of the medial femoral condyle. Similar 'bone marrow oedema changes' are sometimes seen in areas around typical lesions of osteonecrosis.
Metabolic, Degenerative, and Unclassified Conditions Associated With Interstitial Lung Disease
Lourdes R. Laraya-Cuasay, Walter T. Hughes in Interstitial Lung Diseases in Children, 2019
Lung biopsy specimens show diffuse interstitial fibrosis in the alveolar septae and peribronchial fibrosis. Patients who have pulmonary fibrosis must be carefully monitored for the occurrence of viral, bacterial, or mycoplasmal infections and aggressively treated accordingly. The frequency of the disease and the lack of neurological involvement in the adult form of Gaucher disease is particularly worthy of research efforts to develop enzyme replacement therapy. Certain persons with cystic fibrosis may present with mild pulmonary involvement characterized radiographically by mild interstitial pattern unrelated to the presence of respiratory infection. Interstitial pneumonia with mononuclear cells is common in postmortem studies of lungs from persons with cystic fibrosis (CF). Interstitial pneumonia with mononuclear cells is common in postmortem studies of lungs from persons with CF. The prevalence of allergic rhinitis, atopic dermatitis, and allergic asthma in CF is probably equal to that of the normal population.
Progress and potential of non-inhibitory small molecule chaperones for the treatment of Gaucher disease and its implications for Parkinson disease
Published in Expert Review of Proteomics, 2016
Olive Jung, Samarjit Patnaik, Juan Marugan, Ellen Sidransky, Wendy Westbroek
Gaucher disease, caused by pathological mutations GBA1, encodes the lysosome-resident enzyme glucocerebrosidase, which cleaves glucosylceramide into glucose and ceramide. In Gaucher disease, glucocerebrosidase deficiency leads to lysosomal accumulation of substrate, primarily in cells of the reticulo-endothelial system. Gaucher disease has broad clinical heterogeneity, and mutations in GBA1 are a risk factor for the development of different synucleinopathies. Insights into the cell biology and biochemistry of glucocerebrosidase have led to new therapeutic approaches for Gaucher disease including small chemical chaperones. Such chaperones facilitate proper enzyme folding and translocation to lysosomes, thereby preventing premature breakdown of the enzyme in the proteasome. This review discusses recent progress in developing chemical chaperones as a therapy for Gaucher disease, with implications for the treatment of synucleinopathies. It focuses on the development of non-inhibitory glucocerebrosidase chaperones and their therapeutic advantages over inhibitory chaperones, as well as the challenges involved in identifying and validating chemical chaperones.
A case of traction retinal detachment in a patient with Gaucher disease
Published in Ophthalmic Genetics, 2017
Akira Watanabe, Tamaki Gekka, Kota Arai, Hiroshi Tsuneoka
Background: This is the first report of vitreous surgery for traction retinal detachment in a patient with type III Gaucher disease with multiple vitreous opacities. Materials and methods: A 16-year-old boy who was diagnosed with Gaucher disease at age two and was undergoing enzyme replacement therapy presented with numerous white opacities of varying sizes in the vitreous bodies of both eyes. Visual acuity was 20/40 in the right eye and 20/2000 in the left eye. The retina of the left eye was completely detached, and vitreous surgery was performed. Results: Liquefaction of the vitreous body was advanced, and the central part of the vitreous cavity contained almost no vitreous humor. The macular region was successfully aspirated with a vitreous cutter to form a posterior vitreous detachment. From the optic disk to the nasal side, however, posterior vitreous detachment formation was prevented by strong adhesions between the retina and the vitreous body. The traction retinal detachment of the posterior fundus improved after vitreous body resection alone. Conclusions: Traction retinal detachment may occur as a result of severe vitreous liquefaction in cases of Gaucher disease with numerous vitreous opacities.
Analysis of the pre-retinal opacities in Gaucher Disease using spectral domain optical coherent tomography
Published in Ophthalmic Genetics, 2012
Leo H. N. Sheck, Callum J. Wilson, Andrea L. Vincent
Fundal opacities have been reported in patients with Gaucher disease, a rare autosomal recessive lysosomal storage disease, prior to the advent of optical coherent tomography. This report provides a detailed analysis of the fundal opacities in a 14-year-old girl with genetically proven Gaucher disease using spectral domain optical coherent tomography. It illustrates clearly that these opacities were pre-retinal opacities located at the vitreo-retinal interface associated with localized posterior vitreous detachments, rather than vitreous opacities as previously suggested in the literature.
Related Knowledge Centers
- Central Nervous System
- Mononuclear Phagocyte System
- Sphingolipidoses
- Sphingolipids
- Bone Marrow
- Histiocytes
- Glucosylceramidase