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Gaucher disease type 2

Monika Dyczko, Anna Grzywa-Celińska, Wojciech Barud, Rafał Celiński, Wojciech Dworzański, Katarzyna Szmygin-Milanowska, Jerzy Mosiewicz
: Gaucher's disease if one of the most frequent, among extremely rare, lysosomal storage diseases. It is the autosomal recessive inherited metabolic disorder, which can present in three main clinical forms. Type 1 - the most benign, in a not-neuropathic form, and types 2 and 3, both in neuropathic form, which manifest serious neurological symptoms. AIM: The aim of the study was to draw attention to the late diagnosing of Gaucher's disease in the Polish population and to popularize the knowledge about this ultra-rare disease...
July 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Ganqiang Liu, Brendon Boot, Joseph J Locascio, Iris E Jansen, Sophie Winder-Rhodes, Shirley Eberly, Alexis Elbaz, Alexis Brice, Bernard Ravina, Jacobus J van Hilten, Florence Cormier-Dequaire, Jean-Christophe Corvol, Roger A Barker, Peter Heutink, Johan Marinus, Caroline H Williams-Gray, Clemens R Scherzer
OBJECTIVE: We hypothesized that mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes will be associated with aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, while mutations associated with non-neuropathic GD will confer intermediate progression rates. METHODS: 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median 4.1) from seven cohorts were analyzed...
September 22, 2016: Annals of Neurology
Victoria Mallett, Jay P Ross, Roy N Alcalay, Amirthagowri Ambalavanan, Ellen Sidransky, Patrick A Dion, Guy A Rouleau, Ziv Gan-Or
The lysosomal enzyme glucocerebrosidase (GCase), encoded by GBA, has an important role in Parkinson disease (PD). GBA mutation carriers have an increased risk for PD, earlier age at onset, faster progression, and various nonmotor symptoms including cognitive decline, REM sleep behavior disorder, hyposmia, and autonomic dysfunction.(1) Furthermore, GCase enzymatic activity is reduced in the peripheral blood(2) and brain(3) of noncarrier, sporadic PD patients. Biallelic GBA mutations, which have been classified as "severe" or "mild," may cause Gaucher disease (GD), a lysosomal storage disorder...
October 2016: Neurology. Genetics
M S Larroudé, G Aguilar, I Rossi, G Drelichman, N Fernandez Escobar, N Basack, M Slago, A Schenone, A Fynn, M F Cuello, R Fernandez, A Ruiz, P Reichel, N Guelbert, H Robledo, N Watman, M Bolesina, G Elena, S E Veber, G Pujal, G Galvan, J J Chain, A Arizo, J Bietti, M Aznar, M Dragosky, M Marquez, L Feldman, K Muller, S Zirone, G Buchovsky, V Lanza, I Fernandez, R Jaureguiberry, M A Barbieri, A Maro, G Zarate, G Fernandez, M Rapetti, A Degano, G Kantor, A Albina, M Alvarez Bollea, H Arrocena, V Bacciedoni, F Del Rio
The purpose of this study was to evaluate the frequency of osteoporosis (OP) in patients with Gaucher disease (GD) in Argentina. GD patients from 28 centers were consecutively included from April 2012 to 2014. Bone mineral density (BMD) was determined by dual X-ray absorptiometry in the lumbar spine and the femoral neck or the total proximal femur for patients ≥20 yr of age, and by whole-body scan in the lumbar spine in patients <20 yr of age. In children, mineral density was calculated using the chronological age and Z height...
August 26, 2016: Journal of Clinical Densitometry
Alison Van Rossum, Megan Holsopple
BACKGROUND: Gaucher disease is a rare lysosomal storage disease resulting from a deficiency or reduced activity in the acid β-glucocosidase enzyme. Only 1 treatment option was available for 15 years, but several new treatment options have come to market since 2003. OBJECTIVE: The article will detail the pathophysiology and review current therapies in the literature for all 3 major clinical types of Gaucher disease, with a focus on considerations for selecting therapy in type 1 disease...
July 2016: Hospital Pharmacy
Ekaterina A Ivanova, Mohamed A Elmonem, Inge Bongaerts, Tomas Luyten, Ludwig Missiaen, Lambertus P van den Heuvel, Elena N Levtchenko, Geert Bultynck
Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder caused by loss-of-function mutations in the CTNS gene coding for the lysosomal cystine transporter, cystinosin. Recent studies have demonstrated that, apart from cystine accumulation in the lysosomes, cystinosin-deficient cells, especially renal proximal tubular epithelial cells are characterized by abnormal vesicle trafficking and endocytosis, possible lysosomal dysfunction and perturbed intracellular signalling cascades. It is therefore possible that Ca(2+) signalling is disturbed in cystinosis, as it has been demonstrated for other disorders associated with lysosomal dysfunction, such as Gaucher, Niemann-Pick type C and Alzheimer's diseases...
October 2016: Cell Calcium
Mia Horowitz, Deborah Elstein, Ari Zimran, Ozlem Goker-Alpan
In Gaucher disease (GD), mutant lysosomal acid β-glucocerebrosidase fails to properly hydrolyze its substrate, glucosylceramide, which accumulates in the lysosomes. Due to its phenotypic heterogeneity, GD has been classified into type 1, non-neuronopathic, and types 2 and 3, the neuronopathic forms, based on the primary involvement of the central nervous system. Neuroinflammation and necroptotic death may appear in the neuronopathic forms of GD, whereas type 1 GD patients may develop Parkinson disease (PD), a prototype of protein misfolding disorders of the nervous system...
November 2016: Human Mutation
Vagishwari Murugesan, Wei-Lien Chuang, Jun Liu, Andrew Lischuk, Katherine Kacena, Haiqun Lin, Gregory M Pastores, Ruhua Yang, Joan Keutzer, Kate Zhang, Pramod K Mistry
Gaucher disease (GD) leads to accumulation of glucosylceramide (GL1) and its deacylated lysolipid, glucosylsphingosine (lyso-GL1) which is implicated in mediating immune dysregulation and skeletal disease. The aim of our study was to assess plasma Lyso-GL1 as a biomarker of GD and its response to therapy. Plasma lyso-GL1 in 169 patients with GD type 1 (GD1) was measured by LC-MS/MS. Significant predictors of were assessed by Pearson's correlation coefficient, Wilcoxon Mann Whitney test and multiple linear regression...
July 21, 2016: American Journal of Hematology
Guillermo Drelichman, Nicolás Fernández Escobar, Nora Basack, Luis Aversa, María Silvia Larroude, Gabriela Aguilar, Marina Szlago, Andrea Schenone, Alcyra Fynn, María Fernanda Cuello, Marcela Aznar, Ramiro Fernández, Alba Ruiz, Paola Reichel, Norberto Guelbert, Hugo Robledo, Nora Watman, Moira Bolesina, Graciela Elena, S Ernesto Veber, Graciela Pujal, Graciela Galván, Juan José Chain, Adriana Arizo, Julieta Bietti, Daniel Bar, Marta Dragosky, Marisa Marquez, Leonardo Feldman, Katja Muller, Sandra Zirone, Greogorio Buchovsky, Victoria Lanza, Alba Sanabria, Ignacio Fernández, Rossana Jaureguiberry, Marcelo Contte, Angie Barbieri María, Alejandra Maro, Graciela Zárate, Gabriel Fernández, María Cristina Rapetti, Hugo Donato, Adriana Degano, Gustavo Kantor, Roberto Albina, María Á Lvarez Bollea, María Brun, Viviana Bacciedoni, Francis Del Río, Bárbara Soberón, Nazario Boido, Maya Schweri, Sandra Borchichi, Victoria Welsh, Marcela Corrales, Alejandra Cedola, Analía Carvani, Blanca Diez, Lucía Richard, Ccecilia Baduel, Gabriela Nuñez, Rubén Colimodio, Lucía Barazzutti, Hugo Medici, Susana Meschengieser, Germán Damiani, María Nucifora, Beatriz Girardi, Sergio Gómez, Maura Papucci, David Verón, Luis Quiroga, Gustavo Carro, Patricia De Ambrosio, José Ferro, Marcelo Pujol, Cristina Cabral Castella, Liliana Franco, Gisela Nisnovich, María Veloso, Isabel Pacheco, Mario Savarino, Andrés Marino, José Luis Saavedra
Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0...
October 2016: American Journal of Hematology
Elma Aflaki, Daniel K Borger, Nima Moaven, Barbara K Stubblefield, Steven A Rogers, Samarjit Patnaik, Frank J Schoenen, Wendy Westbroek, Wei Zheng, Patricia Sullivan, Hideji Fujiwara, Rohini Sidhu, Zayd M Khaliq, Grisel J Lopez, David S Goldstein, Daniel S Ory, Juan Marugan, Ellen Sidransky
UNLABELLED: Among the known genetic risk factors for Parkinson disease, mutations in GBA1, the gene responsible for the lysosomal disorder Gaucher disease, are the most common. This genetic link has directed attention to the role of the lysosome in the pathogenesis of parkinsonism. To study how glucocerebrosidase impacts parkinsonism and to evaluate new therapeutics, we generated induced human pluripotent stem cells from four patients with Type 1 (non-neuronopathic) Gaucher disease, two with and two without parkinsonism, and one patient with Type 2 (acute neuronopathic) Gaucher disease, and differentiated them into macrophages and dopaminergic neurons...
July 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Huma Arshad Cheema, Hassan Suleman Malik, Arit Parkash, Zafar Fayyaz
OBJECTIVE: To determine the frequency, presentation and outcome of various inherited metabolic diseases in children presenting in a tertiary care hospital, Lahore, Pakistan. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Gastroenterology, Hepatology and Nutrition Department of The Children Hospital and Institute of Child Health, Lahore, from January 2011 to October 2014. METHODOLOGY: All children aged < 14 years with high suspicion of a metabolic disorder were inducted...
June 2016: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Emilia M Gatto, Jose Luis Etcheverry, Ana Sanguinetti, Martin Cesarini, Nicolas Fernandez Escobar, Guillermo Drelichman
Heterozygous mutations in the glucocerebrosidase (GBA) gene have been reported as a common risk factor for the development of Parkinson's disease (PD) in Gaucher disease (GD) patients and in heterozygous GBA mutation positive carriers. In this study, we analyzed the occurrence of prodromal markers of PD in an Argentinean cohort with type 1 GD. After signed informed consent, we evaluated 26 patients with type 1 GD under enzymatic replacement therapy from a cohort of the Hospital Ricardo Gutierrez GD Study Group in Buenos Aires City, Argentina...
2016: European Neurology
Kourtnee Hoitsema, Dominick Amato, Aneal Khan, Sandra Sirrs, Francis Y M Choy
Gaucher disease is an autosomal recessive lysosomal storage disorder resulting from deficient glucocerebrosidase activity. More than 350 mutations that cause Gaucher disease have been described to date. Novel mutations can potentially provide insight into the glucocerebrosidase structure-function relationship and biochemical basis of the disease. Here, we report the identification of two novel mutations in two unrelated patients with type I (non-neuronopathic) Gaucher disease: 1) a splice site mutation IVS9 + 1G > A; and (2) a complex allele (cis) G355R/R359X...
September 2016: Meta Gene
Y Chen Zion, E Pappadopulos, M Wajnrajch, H Rosenbaum
BACKGROUND: Gaucher disease (GD) is a rare lysosomal storage disease caused by deficiency in the enzyme beta-glucocerebrosidase. Along with visceral, hematologic, and bone manifestations, patients may experience chronic fatigue resulting in functional disability and reduced quality of life. Management of the disease includes therapeutic intervention, supportive therapies, and regular monitoring of all clinically relevant disease signs and symptoms. However, current practice guidelines do not include measurement of fatigue or therapeutic goals for fatigue...
2016: Orphanet Journal of Rare Diseases
Nadia Sawicka-Gutaj, Maciej Machaczka, Izabela Kulińska-Niedziela, Jadwiga Bernardczyk-Meller, Paweł Gutaj, Jerzy Sowiński, Marek Ruchała
Background Gaucher disease (GD) is an autosomal recessive lipid storage disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase. The presence of central nervous system disease is a hallmark of the neuronopathic forms of GD (types 2 and 3). Intraocular lesions (e.g. corneal clouding, retinal lesions, and vitreous opacities) have been infrequently reported in GD type 3 (GD3). Moreover, there are virtually no published data on the occurrence and natural course of intraocular lesions in GD3 patients treated with enzyme replacement therapy (ERT)...
August 2016: Upsala Journal of Medical Sciences
Giuliano Mariani, Marzio Perri, Fabrizio Minichilli, Simona Ortori, Silvia Linari, Fiorina Giona, Maja Di Rocco, Maria Domenica Cappellini, Federica Guidoccio, Paola Anna Erba
OBJECTIVE: MRI and (99m)Tc-sestamibi scintigraphy are used to estimate bone marrow infiltration in patients with Gaucher disease (GD), but comparison of data obtained at different institutions is difficult because different scores are employed for semiquantitative assessment. We developed normalized scores for comparing data both within a single method (MRI) and between different methods (MRI versus scintigraphy). MATERIALS AND METHODS: We evaluated 51 patients with type 1 GD (26 women, 25 men; mean age ± SD, 36...
June 2016: AJR. American Journal of Roentgenology
A A Mhanni, M Kozenko, J N Hartley, M Deneau, W El-Matary, C Rockman-Greenberg
Gaucher disease (OMIM #230800) is caused by β-glucosidase deficiency and primarily involves the mononuclear phagocyte system (also called Reticuloendothelial System or Macrophage System). The disease is classified into three main phenotypes based on the presence or absence of neurological manifestations: non-neuronopathic (type 1), acute neuronopathic (type 2) and chronic neuronopathic (type 3). Typical manifestations include hepatosplenomegaly, skeletal deformities, hematological abnormalities, interstitial lung fibrosis and neurodegeneration in neuronopathic cases...
March 2016: Molecular Genetics and Metabolism Reports
Bouwien E Smid, Maria J Ferraz, Marri Verhoek, Mina Mirzaian, Patrick Wisse, Herman S Overkleeft, Carla E Hollak, Johannes M Aerts
BACKGROUND: We retrospectively compared biochemical responses in type 1 Gaucher disease patients to treatment with glycosphingolipid synthesis inhibitors miglustat and eliglustat and ERT. METHODS: Seventeen GD1 patients were included (n = 6 eliglustat, (two switched from ERT), n = 9 miglustat (seven switchers), n = 4 ERT (median dose 60U/kg/m). Plasma protein markers reflecting disease burden (chitotriosidase, CCL18) and lipids reflecting substrate accumulation (glucosylsphingosine, glucosylceramide) were determined...
2016: Orphanet Journal of Rare Diseases
Tiago Koppe, Divair Doneda, Marina Siebert, Livia Paskulin, Matheus Camargo, Kristiane Michelin Tirelli, Filippo Vairo, Liane Daudt, Ida Vanessa D Schwartz
The clinical utility of serum ferritin as a biomarker of disease severity and prognosis in Gaucher disease (GD) is still debated. Here, we aimed to evaluate ferritin and its relation to clinicolaboratory parameters of GD patients seen at the Reference Center for Gaucher Disease of Rio Grande do Sul, Brazil, so as to gather evidence on the utility of ferritin as a biomarker of this condition. A retrospective chart review was performed collecting pre-and posttreatment data from GD patients. Eighteen patients with ferritin levels available before and after treatment were included in the study...
March 2016: Genetics and Molecular Biology
Friederike Zunke, Lisa Andresen, Sophia Wesseler, Johann Groth, Philipp Arnold, Michelle Rothaug, Joseph R Mazzulli, Dimitri Krainc, Judith Blanz, Paul Saftig, Michael Schwake
The lysosomal integral membrane protein type-2 (LIMP-2) plays a pivotal role in the delivery of β-glucocerebrosidase (GC) to lysosomes. Mutations in GC result in Gaucher's disease (GD) and are the major genetic risk factor for the development of Parkinson's disease (PD). Variants in the LIMP-2 gene cause action myoclonus-renal failure syndrome and also have been linked to PD. Given the importance of GC and LIMP-2 in disease pathogenesis, we studied their interaction sites in more detail. Our previous data demonstrated that the crystal structure of LIMP-2 displays a hydrophobic three-helix bundle composed of helices 4, 5, and 7, of which helix 5 and 7 are important for ligand binding...
April 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
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