Clinical Characteristics, Molecular Background, and Survival of Egyptian Patients With Gaucher Disease Over a 20-Year Follow-up

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Amal El-Beshlawy ◽  
Khaled Abdel-Azim ◽  
Amina Abdel-Salam ◽  
Nadine A. Gebril ◽  
Yasmeen M.M. Selim ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Egyptian Patients

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung-Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 63 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harboured the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (10%). Of the 18 patients harbouring the p.G85E mutation, their median age at diagnosis was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. Conclusion The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung-Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. ConclusionThe GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3075 years. Conclusion The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

scholarly journals Healing below the ankle is possible in patients with diabetes mellitus and a forefoot gangrene

2021 ◽  
Vol 9 ◽  
pp. 205031212110291
Author(s):  
Targ Elgzyri ◽  
Jan Apelqvist ◽  
Eero Lindholm ◽  
Hedvig Örneholm ◽  
Magdalena Annersten Gershater
Keyword(s):  
Diabetic Foot ◽  
Clinical Characteristics ◽  
Foot Ulcer ◽  
Major Amputation ◽  
Severe Form ◽  
Foot Ulcers ◽  
Vascular Intervention ◽  
Co Morbidity ◽  
Patients With Diabetes

Background: Forefoot gangrene in patients with diabetes is a severe form of foot ulcers with risk of progress and major amputation. No large cohort studies have examined clinical characteristics and outcome of forefoot gangrene in patients with diabetes. The aim was to examine clinical characteristics and outcome of forefoot gangrene in patients with diabetes admitted to a diabetic foot centre. Methods: Patients with diabetes and foot ulcer consecutively presenting were included if they had forefoot gangrene (Wagner grade 4) at initial visit or developed forefoot gangrene during follow-up at diabetic foot centre. Patients were prospectively followed up until final outcome, either healing or death. The median follow-up period until healing was 41 (3–234) weeks. Results: Four hundred and seventy-six patients were included. The median age was 73 (35–95) years and 63% were males. Of the patients, 82% had cardiovascular disease and 16% had diabetic nephropathy. Vascular intervention was performed in 64%. Fifty-one patients (17% of surviving patients) healed after auto-amputation, 150 after minor amputation (48% of surviving patients), 103 had major amputation (33% of surviving patients) and 162 patients deceased unhealed. Ten patients were lost at follow-up. The median time to healing for all surviving patients was 41 (3–234) weeks; for auto-amputated, 48 (10–228) weeks; for minor amputated, 48 (6–234) weeks; and for major amputation, 32 (3–116) weeks. Conclusion: Healing without major amputation is possible in a large proportion of patients with diabetes and forefoot gangrene, despite these patients being elderly and with extensive co-morbidity.

scholarly journals SAT0267 ROLE OF AGGRESSIVE IMMUNOSUPPRESSION ON SUBGLOTTIC STENOSIS IN GRANULOMATOSIS WITH POLYANGIITIS: RETROSPECTIVE ANALYSIS OF A MONOCENTRIC COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1076.1-1077
Author(s):  
L. Moroni ◽  
L. Giudice ◽  
G. A. Ramirez ◽  
S. Sartorelli ◽  
A. Cariddi ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Clinical Characteristics ◽  
Granulomatosis With Polyangiitis ◽  
Balloon Catheter ◽  
Subglottic Stenosis ◽  
Damage Accrual ◽  
The Mean ◽  
The One

Background:Subglottic stenosis (SGS) is defined as airway narrowing below the vocal cords and is a common and potentially life-threatening manifestation of Granulomatosis with Polyangiitis (GPA), with an estimated prevalence of 16-23% (1). Balloon catheter dilation is effective in GPA-related SGS, but relapses are frequent. Little is known about the role of immunosuppression in this setting.Objectives:to analyse the clinical characteristics of a monocentric GPA cohort, describe phenotype differences among patients with and without SGS and investigate the role of surgical and medical treatments on relapse risk and general outcome.Methods:Biopsy-proven patients with SGS were identified by review of medical charts among a cohort of patients with GPA, classified according to the algorithm of the European Medicine Agency (2). The clinical characteristics of patients with SGS were retrospectively collected over a median follow-up time of 15.9 years and compared to those of patients without SGS.Results:Fourteen patients with SGS-GPA were identified, with a female to male ratio of 1:1 and a prevalence of 29.2% among the cohort. The mean ± SD age at GPA onset was 30.8 ± 14.4 years, with a mean time from GPA diagnosis to SGS onset of 4.7 ± 4.2 years. ANCA were positive in 78.6% (54.0% anti-PR3, 18.1% anti-MPO and 27.9% IFI only). The mean Birmingham Vasculitis Activity Score (BVAS) at onset was 10.0 ± 5.6. The main clinical manifestations associated with SGS were crusty rhinitis (100%), sinusitis (78%), pulmonary disease (72.7%), otitis/mastoiditis (50%), glomerulonephritis (42.9%), orbital pseudotumor (28.6%). Six patients (42.9%) received medical treatment only, other six (42.9%) had one to three balloon dilations and two (14.2%) underwent four or more procedures. Eight patients had no SGS relapse (maximum one dilation) and they all received immunosuppression with rituximab (RTX), cyclophosphamide (CYC) or azathioprine (AZA). All patients who received no immunosuppression, methotrexate (MTX) or mycophenolate (MMF) had at least one relapse. Patients treated with MTX or MMF had a mean relapse-free survival of 13.1 months, which was comparable to the one of patients not receiving medical treatment (40.2 months; p=NS) and shorter than the one of patients receiving CYC or RTX (153.2 months; p=0.032). CYC use also inversely correlated with the number of surgical procedures (r=-0.691, p=0.006). Compared to patients without SGS (31 consecutive patients with at least 4 years of follow-up), patients with SGS-GPA had an earlier disease onset (mean age 30.8 vs 50.4 years; p<0.001), but with lower BVAS (mean 10.0 vs 15.3; p=0.013) and showed a higher prevalence of crusty rhinitis (100% vs 67.7%; p=0.019). No difference was observed in damage accrual over time between the two groups.Conclusion:Subglottic stenosis is highly prevalent in patients with GPA and may define a milder disease subset occurring more frequently in younger patients. MTX and MMF might be insufficient to prevent SGS relapses requiring balloon dilation. Aggressive immunosuppression (CYC or RTX) might have a non-redundant role in this setting and reduce the risk of relapses.References:[1]Quinn KA, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology 2019; 58 (12), 2203-2211.[2]Watts R, et al. Development and validation of a consensus methodology for the classification of the ANCA associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 2007; 66: 222-7.Disclosure of Interests:Luca Moroni: None declared, Laura Giudice: None declared, Giuseppe Alvise Ramirez: None declared, Silvia Sartorelli: None declared, adriana cariddi: None declared, Angelo Carretta: None declared, Enrica Bozzolo: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

scholarly journals POS0826 SKIN LIMITED IGA VASCULITIS IN ADULTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 666.1-666
Author(s):  
A. Hočevar ◽  
J. Ostrovrsnik ◽  
K. Perdan-Pirkmajer ◽  
M. Tomsic ◽  
Z. Rotar
Keyword(s):  
Clinical Characteristics ◽  
Systemic Disease ◽  
Elevated Serum ◽  
Skin Lesions ◽  
Current Smoker ◽  
P Value ◽  
Symptom Duration ◽  
Iga Vasculitis ◽  
Reactive Protein

Background:IgA vasculitis (IgAV) could be limited to skin or evolve into a systemic disease, affecting characteristically joints, gastrointestinal tract and/or kidneys.Objectives:We aimed to look for differences between adult IgAV patients with disease limited to skin compared to systemic IgAV.Methods:Medical records of histologically proven adult IgAV cases, diagnosed between January 2010 and December 2020 at our secondary/tertiary rheumatology centre were analyzed.Results:During the 132-month observation period we identified 328 new IgAV cases (59.5% males, median (IQR) age 64.3 (45.1; 76.1) years). Ninety-four (40.2%) patients had skin limited disease, and the rest systemic IgAV.Clinical differences between skin limited and systemic adult IgAV are presented in table 1. Adults with IgAV limited to skin were significantly older, had less commonly skin lesions above the waistline and a lower level of C reactive protein compared to patients with a systemic disease. There were no differences in the frequency of skin necroses between the compared IgAV subgroups. The frequency of potential vasculitis triggers (prior infections, new medications, malignancy) was similar between the compared subgroups.Table 1.Clinical characteristics of IgA vasculitis patients with skin limited and systemic diseaseClinical characteristicsSkin limited IgAV (94)Systemic IgAV (234)P valueMale gender (%)54.361.50.263Age (years)*68.0 (55.0-80.5)61.5 (41.7-75.8)0.007Current smoker (%)13.821.80.123Antecedent infection (%)28.733.80.434New medication23.423.51.0History of cancer12.810.70.569Symptom duration (days)*7 (5-21)8 (5-14)0.756Purpura above waistline36.255.60.002Skin necroses (%)52.145.70.329ESR /mm/h) *32 (18-52)34 (17-53)0.873CRP (g/l) *13.5 (1-32)30 (11-68)<0.001Elevated serum IgA (%)50.649.10.892Legend: * median and IQR;Follow up data were available for 250 (76.2%) patients. During the follow up of median (IQR) 12.5 (6.8 – 22.4) months 35 patients relapsed (13/70 (18.6%) with skin limited IgAV and 22/180 (12.2%) with systemic IgAV, p= 0.224).Conclusion:Skin limited IgAV was associated with older age and less extensive skin puprura in adults. However, relapses of purpura were as common as in systemic IgAV.Disclosure of Interests:None declared

scholarly journals Clinical outcomes of Japanese atrial fibrillation patients with combined valvular heart disease: the Fushimi AF Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Doi ◽  
K Ishigami ◽  
Y Aono ◽  
S Ikeda ◽  
Y Hamatani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Incidence Rate ◽  
Clinical Outcomes ◽  
Valvular Heart Disease ◽  
Cardiac Death ◽  
Clinical Characteristics ◽  
Valve Disease ◽  
The Impact

Abstract Background We previously reported that valvular heart disease (VHD) was not at the significant risk of stroke/systemic embolism (SE), but was associated with an increased risk of hospitalization for heart failure (HF) in Japanese atrial fibrillation patients. However, the impact of combined VHD on clinical outcomes has been little known. Purpose The aim of this study is to investigate the prevalence of combined VHD and its clinical characteristics and impact on outcomes such as stroke/SE, all-cause death, cardiac death and hospitalization for HF. Method The Fushimi AF Registry is a community-based prospective survey of AF patients in one of the wards of our city which is a typical urban district of Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. In the entire cohort, echocardiography data were available for 3,574 patients. 68 AF patients with prosthetic heart valves were excluded and we compared clinical characteristics and outcomes between 488 single VHD (103 Aortic valve disease (AVD), 315 mitral valve disease (MVD), 70 tricuspid valve disease (TVD)) and 158 combined VHD (46 AVD and MVD, 11 AVD and TVD, 66 MVD and TVD, 35 AVD and MVD and TVD). Result Compared with single VHD, patients with combined VHD were older (combined vs. single VHD: 78.5 vs. 76.0 years, respectively; p&lt;0.01), more likely to have persistent/permanent type AF (73.4% vs. 63.9%, p=0.02) and prescription of warfarin (63.1% vs. 53.8%, p=0.04). Combined VHD was less likely to have diabetes mellitus (13.9% vs. 23.6%, p=0.01) and dyslipidemia (26.6% vs. 40.4%, p&lt;0.01). Sex, body weight, hypertension, pre-existing HF were comparable between the two groups. During the median follow-up of 1,474 days, the incidence rate of stroke/SE was not significantly different between the two groups (1.58 vs. 1.89 per 100 person-years, respectively, log rank p=0.10). The incidence rate of all-cause death (7.35 vs. 5.33, p=0.65), cardiac death (1.20 vs. 0.99, p=0.91) and hospitalization for HF (5.55 vs. 4.43, p=0.53) were also not significantly different. We previously reported AVD had significant impacts on cardiac adverse outcomes in AF patients, and we further analyzed event rates between combined VHD including AVD (AVD and MVD/TVD) and without AVD (MVD and TVD). Combined VHD with AVD group had higher incidence rate of all-cause death (10.7 vs. 5.79, p=0.03) than that without AVD group. However, the incidence rate of stroke/SE (1.98 vs. 1.56, p=0.59), cardiac death (0.98 vs. 1.14, p=0.68), hospitalization for HF (8.03 vs. 5.38, p=0.17) were not significantly different between the two groups. Conclusion As compared with single VHD, the risk of stroke/SE, all-cause death, cardiac death and hospitalization for HF in combined VHD was not significantly different. Among patients with combined VHD, those having AVD had higher incidence rate of all-cause death than those without AVD. Figure 1 Funding Acknowledgement Type of funding source: None

Clinical characteristics and risk factors of arrhythmia during follow‐up of patients with idiopathic ventricular fibrillation

2020 ◽  
Vol 31 (10) ◽  
pp. 2677-2686
Author(s):  
Niels K. Stampe ◽  
Camilla B. Jespersen ◽  
Charlotte Glinge ◽  
Henning Bundgaard ◽  
Jacob Tfelt‐Hansen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ventricular Fibrillation ◽  
Clinical Characteristics ◽  
Idiopathic Ventricular Fibrillation

Abstract 18973: Left Ventricular Function Improvement After Recent MI in Patients Using a Wearable Cardioverter Defibrillator

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Chingping Wan ◽  
Steven J Szymkiewicz
Keyword(s):  
Heart Failure ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Clinical Characteristics ◽  
Treated Group ◽  
Left Ventricular ◽  
Icd Implantation ◽  
Cardioverter Defibrillator ◽  
Wearable Cardioverter Defibrillator

Introduction: The wearable cardioverter defibrillator (WCD) has been used to protect AMI patients with reduced LVEF (≤35%) until ICD evaluation is recommended. The rate of EF improvement (e.g. EF>35%) over the initial 8-12 weeks after AMI has not been reported. METHODS: The manufacturer-maintained registry was searched for AMI patients who received a WCD shock for VT/VF between 05/2008 and 02/2013. The treated group was matched (1: ~4) with event-free WCD patients by ICD-9 code (410.*), gender, age and prescription date. Chart notes were reviewed for clinical characteristics. Follow-up was assessed through the registry and Social Security Death Master File. RESULTS: There were 992 (age=63±12, female=20.2%) AMI patients included in the final analysis, 206 treated by WCD and 786 event-free patients. Median follow-up was 334 days. Mean length of WCD use was 67±506 (median=38) days. Subgroup clinical characteristics are presented in Table 1. In the event-free group, 289 (38.9%) patients showed EF improvement to >35%. Nine (4.5%) in the treated group continued wearing the WCD until EF recovery, while 125 (60.7%) received ICD. Absence of recorded heart failure and/or diabetes were associated with LVEF recovery (p<.0001). CONCLUSION: In our study, almost 40% of AMI patients with initial EF ≤35% had EF improvement in two months. The EF recovery group had lower rates of heart failure and diabetes. WCD allows time for left ventricular function recovery in low EF post MI patients, optimizing ICD implantation decisions.

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