scholarly journals Glucosylsphingosine (lyso-Gb1) as a Biomarker for Monitoring Treated and Untreated Children with Gaucher Disease

2019 ◽  
Vol 20 (12) ◽  
pp. 3033 ◽  
Author(s):  
Noa Hurvitz ◽  
Tama Dinur ◽  
Michal Becker-Cohen ◽  
Claudia Cozma ◽  
Marina Hovakimyan ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Medical Center ◽  
Progressive Increase ◽  
Clinic Visit ◽  
Enzyme Replacement ◽  
Type 3 ◽  
Blood Spot

The role of glucosylsphingosine (lyso-Gb1), a downstream metabolic product of glucosylceramide, for monitoring treated and untreated children with Gaucher disease (GD) has not yet been studied. We reviewed the clinical charts of 81 children (<18 years), 35 with mild type 1 GD (GD1), 34 with severe GD1 and 12 with type 3 GD (GD3), followed at Shaare Zedek Medical Center between 2014–2018. Disease severity for GD1 was based on genotypes. Forty children (87%) with severe GD1 and GD3 received enzyme replacement therapy (ERT) compared to two children (6%) with mild GD1. Lyso-Gb1 measurements were conducted on dried blood spot samples taken at each clinic visit. Lyso-Gb1 levels were significantly lower in children with mild compared to severe GD1 (p = 0.009). In untreated children, lyso-Gb1 levels were inversely correlated with platelet counts. During follow-up, lyso-Gb1 increased in almost 50% of untreated children, more commonly in younger children. In treated children, lyso-Gb1 levels were inversely correlated with hemoglobin levels. The increase of lyso-Gb1 while receiving ERT, seen in eight children, was partly associated with compliance and weight gain. Lyso-Gb1 seems to be a useful biomarker for monitoring children with GD and should be included in the routine follow-up. Progressive increase in lyso-Gb1 levels in untreated children suggests ERT initiation.

Maintenance Efficacy of Low Dose Imiglucerase for Gaucher Disease

2020 ◽  
Author(s):  
Zhengqing Qiu ◽  
Baohui Zhang ◽  
Yuhang Song ◽  
Hongbing Zhang ◽  
Yuting Wu
Keyword(s):  
Gaucher Disease ◽  
Low Dose ◽  
Standard Dose ◽  
Mineral Density ◽  
Recommended Treatment ◽  
Type 3 ◽  
Term Maintenance

Abstract Background Imiglucerase is the recommended treatment for Gaucher disease (GD), a hereditary metabolic disease. In high risk adults and all children, the minimum recommended dose for long-term maintenance is 30 U/kg/2 weeks. However, the extremely high cost of this enzyme largely hinders its clinical use. The minimal maintenance dose of imiglucerase has thus been a subject of debate. We aimed to analyze the long-term maintenance outcomes of imiglucerase at dosage < 20 U/kg/2 weeks after standard dose. Methods Seventeen patients with GD type 1 or GD type 3 were enrolled for analysis. We evaluated maintenance efficacy of imiglucerase on hemoglobin, platelet, visceral volumes and bone conditions during the 7-year follow-up. Results Parameters on hemoglobin, platelet, liver, and spleen volumes of all patients were stabilized or improved. Seven out of 14 patients showed bone mineral density improvement. Three out of 16 patients showed worse bone pain; 6 out of 15 patients showed worse Erlenmeyer flask; 6 out of 15 patients showed worse bone infarction; 1 out of 16 patients showed worse marrow infiltration and 3 out of 15 patients showed worse osteonecrosis. Conclusions Imiglucerase less than 20 U/kg/2 weeks is enough to maintain blood and visceral parameters, but is not sufficient to stabilize skeletal conditions.

scholarly journals Eye Movement Biomarkers Allow for the Definition of Phenotypes in Gaucher Disease

2020 ◽  
Author(s):  
Aimee Donald ◽  
Chong Yew Tan ◽  
Anupam Chakrapani ◽  
Derralyn Hughes ◽  
Reena Sharma ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gaucher Disease ◽  
Saccadic Eye Movements ◽  
Disease Classification ◽  
Clinical Feature ◽  
Enzyme Replacement ◽  
Clinical Endpoints ◽  
Definition Of ◽  
Type 3

Abstract Background Neurological forms of Gaucher disease, the inherited disorder of b-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with Enzyme Replacement Therapy (ERT), however, molecules which cross the blood-brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of ‘type 3’ Gaucher disease. MethodsWe undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups. ResultsWe confirmed the saccadic abnormality in patients with type 3 Gaucher disease andidentified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared aGBA1 variant. ConclusionsThis striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.

scholarly journals Gaucher's Disease- A case report

2014 ◽  
Vol 3 (2) ◽  
pp. 45-48
Author(s):  
ASM Ruhul Quddush ◽  
Md Kamruzzaman ◽  
Md Badruzzaman ◽  
Mirja Hamidul Haque ◽  
Nazma Parvin Ansari ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Abdominal Distension ◽  
Disease Type ◽  
X Ray ◽  
Enzyme Replacement ◽  
Gaucher Disease Type 1 ◽  
Form Type ◽  
Type 3

A 3 years old immunized girl of consanguineous parents presented abdominal distension with hepatosplenomegaly. She was moderately anemic, moderately wasted and stunted. Neurological examination was normal. Musculoskeletal system examination revealed no abnormality. Diagnosis was supported by typical bone involvement in X-ray film (thin cortex in limb bone) and gaucher cell in the bone marrow and also in the splenic aspiration. There are three subtypes Type1: Non neuropathic form, Type 2: Acute neuropathic form, Type 3: Chronic neuropathic form. However some cases do not fit precisely into one of these categories. All forms of Gaucher disease are autosomal recessively inherited. So, this patient more or less correlates with Gaucher disease type 1. Treatment option for type 1 and 3 include medicine and enzyme replacement therapy, which is usually very effective. CBMJ 2014 July: Vol. 03 No. 02 P: 45-48

scholarly journals PP044 Adherence To Enzyme Replacement Therapy In Gaucher Disease

2017 ◽  
Vol 33 (S1) ◽  
pp. 91-92
Author(s):  
Amanda Quevedo ◽  
Alicia Dornelles ◽  
Livia Paskulin ◽  
Taciane Alegra ◽  
Barbara Krug ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gaucher Disease ◽  
High Rate ◽  
Reference Center ◽  
Enzyme Replacement ◽  
Brazilian Government ◽  
Type 3 ◽  
Very High

INTRODUCTION:Gaucher disease (GD) is a genetic autosomic disorder for which treatment has been funded by the Brazilian government since the 1990s. In our state most patients are treated with enzyme replacement therapy (ERT) and followed by our Reference Center under the recommendation of the Ministry of Health Brazilian guidelines. There is a lack in the literature about adherence of patients to treatment. The objective was to describe adherence to the treatment in a cohort of all GD patients in the southern state of Brazil.METHODS:This was a cohort study of all GD patients treated with velaglucerase α, taliglucerase α and imiglucerase from January 2010 to January 2015. Adherence was measured as recommended by the Brazilian guidelines as to perform more than 50 percent of the anticipated infusions per year.RESULTS:Our study included thirty-seven patients of both genders. Doses of ERT varied from 15 to 45IU/kg for type 1 patients and from 30 to 60 IU/kg for type 3 patients. A mean of 83 percent of anticipated infusions were performed and from all patients only one did not adhere to the treatment during the 5 years of our study. The majority of the patients performed at least 50 percent of all anticipated infusions.CONCLUSIONS:We noted a very high rate of adherence to treatment with a very few adverse effects. Our data might be showing that the very high rate of adherence in these chronic disease patients may be attributed to the value of treatment by patients and their family, and also due to the existence of a multidisciplinary team at the reference center. These data might be useful for public health policy making in other countries.

scholarly journals Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Aimee Donald ◽  
Chong Y. Tan ◽  
Anupam Chakrapani ◽  
Derralyn A. Hughes ◽  
Reena Sharma ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gaucher Disease ◽  
Saccadic Eye Movements ◽  
Disease Classification ◽  
Clinical Feature ◽  
Enzyme Replacement ◽  
Clinical Endpoints ◽  
Definition Of ◽  
Type 3

Abstract Background Neurological forms of Gaucher disease, the inherited disorder of β-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with enzyme replacement therapy, however, molecules which cross the blood–brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of ‘type 3’ Gaucher disease. Methods We undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video-oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups. Results We confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared a GBA1 variant. Conclusions This striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.

scholarly journals Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease

2020 ◽  
Author(s):  
Aimee Donald ◽  
Chong Yew Tan ◽  
Anupam Chakrapani ◽  
Derralyn Hughes ◽  
Reena Sharma ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gaucher Disease ◽  
Saccadic Eye Movements ◽  
Disease Classification ◽  
Clinical Feature ◽  
Enzyme Replacement ◽  
Clinical Endpoints ◽  
Definition Of ◽  
Type 3

Abstract Background Neurological forms of Gaucher disease, the inherited disorder of β-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with Enzyme Replacement Therapy (ERT), however, molecules which cross the blood-brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of ‘type 3’ Gaucher disease. Methods We undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups. Results We confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared a GBA1 variant. Conclusions This striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.

Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

2020 ◽  
Vol 16 (8) ◽  
pp. 807-819 ◽  
Author(s):  
Madalena Sousa ◽  
Jácome Bruges-Armas
Keyword(s):  
Diabetes Mellitus ◽  
Complex Disease ◽  
Clinical Manifestations ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Diabetes Genetics ◽  
Individualize Treatment

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

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