Dataset Information

Characteristics of Pompe disease in China: a report from the Pompe registry.

ABSTRACT: BACKGROUND:Pompe disease is a rare, progressive, autosomal recessive lysosomal storage disorder caused by mutations in the acid ?-glucosidase gene. This is the first report of Chinese patients from the global Pompe Registry. Chinese patients enrolled in the Registry ( ClinicalTrials.gov , NCT00231400) between Jan 2013 and 2 Sep 2016 with late onset Pompe disease (LOPD; presentation after 12?months of age or presentation at ?12?months without cardiomyopathy) were included. Data analyses were descriptive. RESULTS:Of the 59 Chinese patients included, 86.4% had never received enzyme replacement therapy (ERT). The age at symptom onset and diagnosis was 14.9 (12.35) and 22.1 (10.08) years, which is younger than previous reports of LOPD patients from the rest of the world (28.4 [18.86] and 34.9 [20.03], respectively). The most common diagnosis methods were enzyme assay (79.7%) and/or DNA analysis (61.0%). Of the 36 patients diagnosed using DNA analysis, 31 had standardized variant data and among these patients the most common mutations were c.2238G?>?C (n?=?18, 58.1%) and c.2662G?>?T (n?=?5, 16.1%). Chinese LOPD patients appeared to have worse lung function versus patients from the rest of the world, indicated by lower forced vital capacity (37.2 [14.00]% vs. 63.5 [26.71]%) and maximal expiratory and inspiratory pressure (27.9 [13.54] vs. 51.0 [38.66] cm H2O, and 29.4 [12.04] vs. 70.5 [52.78] cm H2O). CONCLUSIONS:Compared with patients from the rest of the world, Chinese patients with LOPD appeared to have younger age at symptom onset and diagnosis, lower lung function, and the majority had not received ERT. The most common mutations were c.2238G?>?C and c.2662G?>?T.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6448270 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Characteristics of Pompe disease in China: a report from the Pompe registry.

Zhao Yuying Y Wang Zhaoxia Z Lu Jiahong J Gu Xuefan X Huang Yonglan Y Qiu Zhengqing Z Wei Yanping Y Yan Chuanzhu C

Orphanet journal of rare diseases 20190403 1

<h4>Background</h4>Pompe disease is a rare, progressive, autosomal recessive lysosomal storage disorder caused by mutations in the acid α-glucosidase gene. This is the first report of Chinese patients from the global Pompe Registry. Chinese patients enrolled in the Registry ( ClinicalTrials.gov , NCT00231400) between Jan 2013 and 2 Sep 2016 with late onset Pompe disease (LOPD; presentation after 12 months of age or presentation at ≤12 months without cardiomyopathy) were included. Data analyses w ...[more]

PMID: 30943998

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Project description:BackgroundPompe disease (PD) is a rare, progressive, and autosomal recessive lysosomal storage disorder caused by mutations in the acid α-glucosidase gene. The clinical course and molecular mechanism of this disease in China have not been well defined.MethodsIn this single-center cohort study, we investigated a total of 15 Chinese patients with Pompe disease to better understand the clinical manifestations, echocardiographic imaging and genetic characteristics in this population.ResultsThe median age of 15 patients at symptom onset was 5.07 months (1-24 months). The median age at diagnosis was 19.53 months (range: 3 to 109 months, n = 15). Average diagnostic delay was 13.46 months. None of the patients had received enzyme replacement therapy (ERT). Fifteen patients died at a median age of 24.80 months due to cardiorespiratory failure (range 3-120 months). Myasthenia symptoms and severe hypertrophic cardiomyopathy were universally present (15/15 = 100%). Global longitudinal strain (GLS) by echocardiography was significantly lower in these patients. After adjusting for gender, body surface area (BSA), left ventricular ejection fraction (LVEF), E/e'ratio, maximum left ventricular wall thickness (MLVWT), left ventricular posterior wall (LVPW), left ventricular outflow tract (LVOT)gradient, GLS was independently correlated with survival time (hazard ratio (HR) = 0.702, 95% confidence Interval (CI): 0.532-0.925, P = 0.012). In our cohort, we identified 4 novel GAA mutation: c.2102T > C (p.L701P), c.2006C > T (p.P669l), c.766T > A (p.Y256N), c.2405G > T (p.G802V). 12 patients were compound heterozygotes, and 4 homozygotes.ConclusionsOur study provides a comprehensive examination of PD clinical course and mutations of the GAA gene for patients in China. We showed clinical utility of echocardiography in quantifying heart involvement in patients with suspected PD. GLS can provide prognostic information for mortality prediction. We reported four novel mutations in the GAA gene for the first time. Our findings may improve early recognition of PD characteristics in Chinese patients.

Project description:BackgroundThe past decade has witnessed an ever-increasing momentum of transcatheter aortic valve replacement (TAVR) and a subsequent paradigm shift in the contemporary management of severe aortic stenosis (AS). We conducted a multi-centric TAVR registry based on Chinese patients (the China Aortic valve tRanscatheter Replacement registrY [CARRY]) to delineate the clinical characteristics and outcomes of Chinese patients who underwent TAVR and compare the results between different valve types in different Chinese regions.MethodsCARRY is an all-comer registry of aortic valve disease patients undergoing TAVR across China and was designed as an observational study that retrospectively included all TAVR patients at each participating site. Seven hospitals in China participated in the CARRY, and 1204 patients from April 2012 to November 2020 were included. Categorical variables were compared using the chi-squared test, and continuous variables were analyzed using a t test or analysis of variance (ANOVA) test. The Kaplan-Meier curve was used to estimate the risk of adverse events during follow-up.ResultsThe mean age of the patients was 73.8 ± 6.5 years and 57.2% were male. The median Society of Thoracic Surgeon-Predicted Risk of Mortality score was 6.0 (3.7-8.9). Regarding the aortic valve, the proportion of bicuspid aortic valve (BAV) was 48.5%. During the hospital stay, the stroke rate was 0.7%, and the incidence of high-degree atrioventricular block indicating permanent pacemaker implantation was 11.0%. The in-hospital all-cause mortality rate was 2.2%. After 1 year, the overall mortality rate was 4.5%. Compared to patients with tricuspid aortic valve (TAV), those with BAV had similar in-hospital complication rates, but a lower incidence of in-hospital mortality (1.4% vs. 3.3%) and 1 year mortality (2.3% vs. 5.8%).ConclusionsTAVR candidates in China were younger, higher proportion of BAV, and had lower rates of post-procedural complications and mortality than other international all-comer registries. Given the use of early generation valves in the majority of the population, patients with BAV had similar rates of complications, but lower mortality than those with TAV. These findings further propel the extension of TAVR in low-risk patients.Trial registrationhttps://www.chictr.org.cn/ (No. ChiCTR2000038526).

Project description:BACKGROUND:Pompe disease is a lysosomal storage disorder caused by the deficiency of acid alpha-glucosidase (EC. 3.2.1.20) due to mutations in human GAA gene. The objective of the present study was to examine clinical and molecular characteristics of infantile-onset Pompe disease (IOPD) in Thailand. METHODS:Twelve patients with infantile-onset Pompe disease (IOPD) including 10 Thai and two other Asian ethnicities were enrolled. To examine the molecular characteristics of Pompe patients, GAA gene was analyzed by PCR amplification and direct Sanger-sequencing of 20 exons coding region. The novel mutations were transiently transfected in COS-7 cells for functional verification. The severity of the mutation was rated by study of the GAA enzyme activity detected in transfected cells and culture media, as well as the quantity and quality of the proper sized GAA protein demonstrated by western blot analysis. The GAA three dimensional structures were visualized by PyMol software tool. RESULTS:All patients had hypertrophic cardiomyopathy, generalized muscle weakness, and undetectable or?<?1% of GAA normal activity. Three patients received enzyme replacement therapy with variable outcome depending on the age of the start of enzyme replacement therapy (ERT). Seventeen pathogenic mutations including four novel variants: c.876C?>?G (p.Tyr292X), c.1226insG (p.Asp409GlyfsX95), c.1538G?>?A (p.Asp513Gly), c.1895?T?>?G (p.Leu632Arg), and a previously reported rare allele of unknown significance: c.781G?>?A (p.Ala261Thr) were identified. The rating system ranked p.Tyr292X, p. Asp513Gly and p. Leu632Arg as class "B" and p. Ala261Thr as class "D" or "E". These novel mutations were located in the N-terminal beta-sheet domain and the catalytic domain. CONCLUSIONS:The present study provides useful information on the mutations of GAA gene in the underrepresented population of Asia which are more diverse than previously described and showing the hotspots in exons 14 and 5, accounting for 62% of mutant alleles. Almost all mutations identified are in class A/B. These data can benefit rapid molecular diagnosis of IOPD and severity rating of the mutations can serve as a partial substitute for cross reactive immunological material (CRIM) study.

Dataset Information

Characteristics of Pompe disease in China: a report from the Pompe registry.

Publications

Characteristics of Pompe disease in China: a report from the Pompe registry.

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