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    1735 results match your criteria Glycogen Storage Disease Type II Pompe Disease

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    Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease.
    Chin Med J (Engl) 2018 Feb;131(4):448-453
    Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853; School of Medicine, Nankai University, Tianjin 300071, China.
    Background: Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations. Read More

    Insulin-resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria?
    J Inherit Metab Dis 2018 Feb 12. Epub 2018 Feb 12.
    Department of Translational Medical Science, Section of Pediatrics, Federico II University, Via Sergio Pansini, 5, 80131, Naples, Italy.
    Background: Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Read More

    High Sustained Antibody Titers in Patients with Classic Infantile Pompe Disease Following Immunomodulation at Start of Enzyme Replacement Therapy.
    J Pediatr 2018 Feb 7. Epub 2018 Feb 7.
    Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Pediatrics, Division of Metabolic Diseases and Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address:
    Objective: To evaluate whether immunomodulation at start of enzyme replacement therapy induces immune tolerance to recombinant human acid alpha-glucosidase (rhGAA) in patients with classic infantile Pompe disease.

    Study Design: Three patients (1 cross reactive immunologic material negative, 2 cross reactive immunologic material positive) were treated with 4 weekly doses of rituximab, weekly methotrexate, and monthly intravenous immunoglobulin and enzyme replacement therapy at 40 mg/kg/week. Antibody titers were measured using enzyme-linked immunosorbent assay. Read More

    Infantile-onset Pompe disease with neonatal debut: A case report and literature review.
    Medicine (Baltimore) 2017 Dec;96(51):e9186
    Department of Neonatology-Pediatrics.
    Rationale: Infantile-onset Pompe disease, also known as glycogen storage disease type II, is a progressive and fatal disorder without treatment. Enzyme replacement therapy with recombinant human acid alpha-glucosidase (GAA) enhances survival; however, the best outcomes have been achieved with early treatment.

    Patient Concerns: We report a case of a newborn with infantile-onset Pompe disease diagnosed in the first days of life who did not undergo universal neonatal screening. Read More

    Quantification of intramuscular fat in patients with late-onset Pompe disease by conventional magnetic resonance imaging for the long-term follow-up of enzyme replacement therapy.
    PLoS One 2018 9;13(1):e0190784. Epub 2018 Jan 9.
    Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
    Objective: The objective of this study was to evaluate a quantitative method based on conventional T1-weighted magnetic resonance (MR) imaging to assess fatty muscular degeneration in patients with late-onset Pompe disease and to compare it with semi-quantitative visual evaluation (the Mercuri score). In addition, a long-term retrospective data analysis was performed to evaluate treatment response to enzyme replacement therapy with alglucosidase alfa.

    Methods: MR images of the lumbar spine were acquired in 41 patients diagnosed with late-onset Pompe disease from 2006 through 2015. Read More

    Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation.
    Mol Genet Metab 2018 Feb 23;123(2):92-96. Epub 2017 Dec 23.
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. Electronic address:
    Patients with Pompe disease have realized significant medical benefits due to enzyme replacement therapy (ERT) infusions with alglucosidase alfa. However, regular infusions are time-consuming. Utilizing recommended infusion rates, infusion duration is 3h 45min for a patient receiving the standard dose of 20mg/kg, not including additional time needed for preparation of ERT, assessment of vital signs, intravenous access, and post-infusion monitoring. Read More

    Four unreported types of glycans containing mannose-6-phosphate are heterogeneously attached at three sites (including newly found Asn 233) to recombinant human acid alpha-glucosidase that is the only approved treatment for Pompe disease.
    Biochem Biophys Res Commun 2018 01 20;495(4):2418-2424. Epub 2017 Dec 20.
    Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06944, South Korea. Electronic address:
    Myozyme is a recombinant human acid alpha-glucosidase (rhGAA) that is currently the only drug approved for treating Pompe disease, and its low efficacy means that a high dose is required. Mannose-6-phosphate (M6P) glycosylation on rhGAA is a key factor influencing lysosomal enzyme targeting and the efficacy of enzyme replacement therapy (ERT); however, its complex structure and relatively small quantity still remain to be characterized. This study investigated M6P glycosylation on rhGAA using liquid chromatography (LC)-electrospray ionization (ESI)-high-energy collisional dissociation (HCD) tandem mass spectrometry (MS/MS). Read More

    Aberrant proliferation and differentiation of glycogen storage disease type Ib mesenchymal stem cells.
    FEBS Lett 2018 Jan 3;592(2):162-171. Epub 2018 Jan 3.
    Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong, Korea.
    Glycogen storage disease type Ib (GSD-Ib) is caused by mutations of the glucose-6-phosphate transporter (G6PT) and characterized by disrupted glucose homeostasis, neutropenia, and neutrophil dysfunction. To investigate the role of G6PT in human adipose-derived mesenchymal stem cells (hMSCs), the G6PT gene was mutated by CRISPR/Cas9 technology and single cell-derived G6PThMSCs were established. G6PThMSCs have significantly increased cell proliferation but impaired adipogenesis and osteogenesis. Read More

    Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase.
    Sci Transl Med 2017 Nov;9(418)
    INTEGRARE, Genethon, Inserm, Univ Evry, Université Paris-Saclay, 91002 Evry, France.
    Glycogen storage disease type II or Pompe disease is a severe neuromuscular disorder caused by mutations in the lysosomal enzyme, acid α-glucosidase (GAA), which result in pathological accumulation of glycogen throughout the body. Enzyme replacement therapy is available for Pompe disease; however, it has limited efficacy, has high immunogenicity, and fails to correct pathological glycogen accumulation in nervous tissue and skeletal muscle. Using bioinformatics analysis and protein engineering, we developed transgenes encoding GAA that could be expressed and secreted by hepatocytes. Read More

    Exercising with blocked muscle glycogenolysis: Adaptation in the McArdle mouse.
    Mol Genet Metab 2018 Jan 21;123(1):21-27. Epub 2017 Nov 21.
    Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address:
    Background: McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. Read More

    The Role of Genetic Counseling in Pompe Disease After Patients Are Identified Through Newborn Screening.
    Pediatrics 2017 Jul;140(Suppl 1):S46-S50
    Department of Medical Genetics and Genomic Medicine, Saint Peter's University Hospital, New Brunswick, New Jersey
    An important part of the coordinated care by experienced health care teams for all Pompe disease patients, whether diagnosed through newborn screening (NBS), clinical diagnosis, or prenatal diagnosis, is genetic counseling. Genetic counseling helps families better understand medical recommendations and options presented by the patient's health care team so they can make informed decisions. In addition to providing important information about the inheritance and genetic risks, genetic counseling also provides information about Pompe disease and available treatments and resources and should be offered to families with an affected child and all adults diagnosed with Pompe disease. Read More

    Management of Confirmed Newborn-Screened Patients With Pompe Disease Across the Disease Spectrum.
    Pediatrics 2017 Jul;140(Suppl 1):S24-S45
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
    After a Pompe disease diagnosis is confirmed in infants identified through newborn screening (NBS), when and if to start treatment with enzyme replacement therapy (ERT) with alglucosidase alfa must be determined. In classic infantile-onset Pompe disease, ERT should start as soon as possible. Once started, regular, routine follow-up is necessary to monitor for treatment effects, disease progression, and adverse effects. Read More

    The Initial Evaluation of Patients After Positive Newborn Screening: Recommended Algorithms Leading to a Confirmed Diagnosis of Pompe Disease.
    Pediatrics 2017 Jul;140(Suppl 1):S14-S23
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
    Newborn screening (NBS) for Pompe disease is done through analysis of acid α-glucosidase (GAA) activity in dried blood spots. When GAA levels are below established cutoff values, then second-tier testing is required to confirm or refute a diagnosis of Pompe disease. This article in the "Newborn Screening, Diagnosis, and Treatment for Pompe Disease" guidance supplement provides recommendations for confirmatory testing after a positive NBS result indicative of Pompe disease is obtained. Read More

    Newborn Screening for Pompe Disease.
    Pediatrics 2017 Jul;140(Suppl 1):S4-S13
    Medical Genetics Service, Hospital de Clinicas de Porto Alegre (HCPA) and Department of Genetics, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
    Started in 1963 by Robert Guthrie, newborn screening (NBS) is considered to be one of the great public health achievements. Its original goal was to screen newborns for conditions that could benefit from presymptomatic treatment, thereby reducing associated morbidity and mortality. With advances in technology, the number of disorders included in NBS programs increased. Read More

    Enzyme replacement therapy for infantile-onset Pompe disease.
    Cochrane Database Syst Rev 2017 11 20;11:CD011539. Epub 2017 Nov 20.
    Department of Pharmacy, West China Second University Hospital, Sichuan University, No. 20, Section 4, Renmin South Road, Chengdu, China, 610041.
    Background: Infantile-onset Pompe disease is a rare and progressive autosomal-recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Current treatment involves enzyme replacement therapy (with recombinant human alglucosidase alfa) and symptomatic therapies (e.g. Read More

    Sensitivity of whole exome sequencing in detecting infantile- and late-onset Pompe disease.
    Mol Genet Metab 2017 Dec 17;122(4):189-197. Epub 2017 Oct 17.
    Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. Electronic address:
    Pompe disease is a metabolic myopathy with a wide spectrum of clinical presentation. The gold-standard diagnostic test is acid alpha-glucosidase assay on skin fibroblasts, muscle or blood. Identification of two GAA pathogenic variants in-trans is confirmatory. Read More

    Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study.
    Neurology 2017 Dec 8;89(23):2365-2373. Epub 2017 Nov 8.
    From the Erasmus MC University Medical Center (E.K., S.C.A.W., J.M.d.V., E.B., P.A.v.D., N.A.M.E.v.d.B.), Center for Lysosomal and Metabolic Diseases, Department of Neurology; Erasmus MC University Medical Center-Sophia Children's Hospital (M.E.K., J.C.v.d.M., A.T.v.d.P.), Center for Lysosomal and Metabolic Diseases, Department of Pediatrics; Erasmus MC University Medical Center (M.M.F.), Center for Lysosomal and Metabolic Diseases, Department of Rehabilitation Medicine and Physical Therapy; and Erasmus MC University Medical Center (D.R.), Department of Biostatistics, Rotterdam, the Netherlands.
    Objective: To determine the effect of enzyme replacement therapy (ERT) after 5 years and to identify predictors for a favorable response because few data are available on the long-term efficacy of ERT in Pompe disease.

    Methods: We included 102 adult patients with Pompe disease in a nationwide, prospective cohort study. We assessed muscle strength (manual muscle testing with Medical Research Council [MRC] grading, handheld dynamometry [HHD]), muscle function (6-minute walk test, Quick Motor Function Test), daily life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale), and pulmonary function (forced vital capacity [FVC] in upright and supine positions, maximum inspiratory and expiratory pressures) at 3- to 6-month intervals before and after the start of ERT. Read More

    N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease.
    J Med Chem 2017 Dec 22;60(23):9462-9469. Epub 2017 Nov 22.
    Department of Chemical Sciences, Università degli Studi di Napoli Federico II , via Cintia, 80126 Napoli, Italy.
    The highly stereocontrolled de novo synthesis of l-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. l-NBDNJ is able to enhance lysosomal α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human α-glucosidase. In addition, differently from its d-enantiomer, l-NBDNJ does not act as a glycosidase inhibitor. Read More

    Muscle ultrasound: A useful tool in newborn screening for infantile onset pompe disease.
    Medicine (Baltimore) 2017 Nov;96(44):e8415
    aDepartment of Radiology bDepartment of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
    Our study aimed to evaluate the utility of muscle ultrasound in newborn screening of infantile-onset Pompe disease (IOPD) and to establish a system of severity grading. We retrospectively selected 35 patients with initial low acid alpha-glucosidase (GAA) activity and collected data including muscle ultrasound features, GAA gene mutation, activity/performance, and pathological and laboratory findings. The echogenicity of 6 muscles (the bilateral vastus intermedius, rectus femoris, and sartorius muscles) was compared to that of epimysium on ultrasound and rated either 1 (normal), 2 (mildly increased), or 3 (obviously increased). Read More

    Clinical characteristics and muscle glycogen concentrations in warmblood horses with polysaccharide storage myopathy.
    Am J Vet Res 2017 Nov;78(11):1305-1312
    OBJECTIVE To characterize clinical findings for polysaccharide storage myopathy (PSSM) in warmblood horses with type 1 PSSM (PSSM1; caused by mutation of the glycogen synthase 1 gene) and type 2 PSSM (PSSM2; unknown etiology). SAMPLE Database with 3,615 clinical muscle biopsy submissions. PROCEDURES Reported clinical signs and serum creatine kinase (CK) and aspartate aminotransferase (AST) activities were retrospectively analyzed for horses with PSSM1 (16 warmblood and 430 nonwarmblood), horses with PSSM2 (188 warmblood and 646 nonwarmblood), and warmblood horses without PSSM (278). Read More

    Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy.
    Mol Genet Metab 2018 Feb 13;123(2):85-91. Epub 2017 Oct 13.
    Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA. Electronic address:
    Background: Recombinant human acid α-glucosidase (rhGAA) enzyme replacement therapy (ERT) has prolonged survival in infantile Pompe disease (IPD), but has unmasked central nervous system (CNS) changes.

    Methods: Brain imaging, consisting of computed tomography (CT) and/or magnetic resonance imaging (MRI), was performed on 23 patients with IPD (17 CRIM-positive, 6 CRIM-negative) aged 2-38months. Most patients had baseline neuroimaging performed prior to the initiation of ERT. Read More

    [Clinical characteristics and GAA gene mutation in children with glycogen storage disease type II: an analysis of 3 cases].
    Zhongguo Dang Dai Er Ke Za Zhi 2017 Oct;19(10):1092-1097
    Department of Pediatrics, Third Xiangya Hospital of Central South University, Changsha 410013, China.
    Glycogen storage disease type II (GSD II) is an autosomal recessive disorder caused by a deficiency of the lysosomal glycogen-hydrolyzing enzyme acid α-glucosidase (GAA) and can affect multiple systems including the heart and skeletal muscle. The aim of this study was to investigate three children with GSD II confirmed by GAA gene analysis and to report their clinical characteristics and gene mutations. One case was classified as infantile-onset GSD II, and two cases as late-onset GSD II. Read More

    Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant.
    Mol Genet Metab 2017 Nov 19;122(3):99-107. Epub 2017 Sep 19.
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. Electronic address:
    Objective: Newborn screening (NBS) has led to early diagnosis and early initiation of treatment for infantile onset Pompe Disease (IOPD). However, guidelines for management of late onset Pompe disease (LOPD) via NBS, especially with the IVS c.-32-13T>G are not clear. Read More

    [First cases of Pompe's disease in Kazakhstan].
    Zh Nevrol Psikhiatr Im S S Korsakova 2017;117(8):85-87
    Scientific-Practical Center Smagul Kaishibayev Institute of Neurology, Almaty, Kazakhstan.
    The article presents the clinical observations of two newly diagnosed patients with Pompe disease in the Republic of Kazakhstan, confirmed by genetic research. Read More

    Three cases of multi-generational Pompe disease: Are current practices missing diagnostic and treatment opportunities?
    Am J Med Genet A 2017 Oct 1;173(10):2628-2634. Epub 2017 Aug 1.
    Duke University Medical Center, Durham, North Carolina.
    Pompe disease (Glycogen storage disease type II, GSDII, or acid maltase deficiency) is an autosomal recessive metabolic myopathy with a broad clinical spectrum, ranging from infantile to late-onset presentations. In 2015, Pompe disease was added as a core condition to the Recommended Uniform Screening Panel for state newborn screening (NBS). The clinical importance of Pompe disease is evolving with the use of NBS, increasing awareness of the disease, and higher than previously reported disease prevalence; however, current practices miss additional diagnostic and potential treatment opportunities in close relatives of the family proband. Read More

    Improvement of bone mineral density after enzyme replacement therapy in Chinese late-onset Pompe disease patients.
    BMC Res Notes 2017 Jul 28;10(1):351. Epub 2017 Jul 28.
    Department of Radiology, Princess Margaret Hospital, Kowloon, Hong Kong SAR.
    Objective: Late-onset Pompe disease (LOPD) is a lysosomal storage disease resulted from deficiency of the enzyme acid α-glucosidase. Patients usually develop a limb-girdle pattern of myopathy and respiratory impairment, and enzyme replacement therapy (ERT) is the only specific treatment available. Recently, LOPD has been associated with low bone mineral density (BMD), but the effect of ERT on BMD is inconclusive. Read More

    First clinical and genetic description of a family diagnosed with late-onset Pompe disease from Costa Rica.
    Neuromuscul Disord 2017 Oct 20;27(10):951-955. Epub 2017 Jun 20.
    University Hospital of Nice, Cote d'Azur University, France.
    Glycogen storage disease type II, also known as Pompe disease, is an autosomal recessive disorder caused by deficiency of enzymatic activity of acid alpha-glucosidase. The wide phenotypical variation of this disease relates to the amount of residual enzymatic activity depending on the combination of mutations on each allele. We confirmed Pompe disease in a patient that presented with progressive weakness, recurrent episodes of respiratory failure associated with pneumonia, a predominantly demyelinating mixed sensorimotor polyneuropathy and paraspinal complex repetitive discharges. Read More

    Unusual Presentation of Atypical Infantile Pompe Disease in the Newborn Period with Left Ventricular Hypertrophy.
    J Clin Diagn Res 2017 May 1;11(5):SD01-SD02. Epub 2017 May 1.
    Senior Resident, Department of Paediatrics, VMMC and Safdarjung Hospital, New Delhi, India.
    Pompe disease, also known as glycogen storage disease Type II, is a lysosomal storage disorder caused by α-glucosidase deficiency. In general, the clinical spectrum varies with respect to the age of onset, residual enzyme activity and organ involvement. Infantile onset disease has two subtypes: classical and non-classical (atypical). Read More

    Next generation deep sequencing corrects diagnostic pitfalls of traditional molecular approach in a patient with prenatal onset of Pompe disease.
    Am J Med Genet A 2017 Sep 28;173(9):2500-2504. Epub 2017 Jun 28.
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
    Pompe disease is a rare inherited metabolic disorder of glycogen metabolism caused by mutations in the GAA gene, encoding the acid α-1,4 glucosidase. Successful diagnosis of Pompe disease is achieved by clinical and biochemical evaluation followed by confirmation with DNA testing. Here, we report a male infant with a prenatal onset of cardiac symptoms and enzyme testing consistent with Pompe disease, but DNA testing by Sanger sequencing revealed no pathogenic variants. Read More

    Restrictive Arteriopathy in Late-Onset Pompe Disease: Case Report and Review of the Literature.
    J Stroke Cerebrovasc Dis 2017 Aug 21;26(8):e172-e175. Epub 2017 Jun 21.
    Neurovascular Imaging Research Core, University of California, Los Angeles, California.
    Late-onset Pompe disease (LOPD) is an adult type of classical Pompe disease and presents without cardiomyopathy. Neuroimaging in LOPD is typically limited to posterior circulation and involves dilative arteriopathy, especially dolichoectasia and intracranial aneurysms. We report an interesting case of an established diagnosis of asymptomatic LOPD in a young man with a restrictive-variant pattern in posterior vasculature. Read More

    Glycogen Reduction in Myotubes of Late-Onset Pompe Disease Patients Using Antisense Technology.
    Mol Ther 2017 Sep 16;25(9):2117-2128. Epub 2017 Jun 16.
    International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano, 34149 Trieste, Italy. Electronic address:
    Glycogen storage disease type II (GSDII) is a lysosomal disorder caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme, leading to the accumulation of glycogen within the lysosomes. The disease has been classified in infantile and late-onset forms. Most late-onset patients share a splicing mutation c. Read More

    [Clinical and gene mutation analysis of three children with late-onset glycogen storage disease type Ⅱ with hypertrophic cardiomyopathy].
    Zhonghua Er Ke Za Zhi 2017 Jun;55(6):423-427
    Department of Pediatric Endocrinology and Genetics, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
    To investigate the clinical and laboratory features of three children with late-onset type Ⅱ glycogen storage disease(GSD) who presented with hypertrophic cardiomyopathy and to analyze the effect of five mutations identified on the acid-α-glucosidase (GAA) activity and stability.Three cases of children with muscle weakness were included in this study.GAA activity was analyzed in Dried Blood Spot of the patients. Read More

    Critical Airway Stenosis in an Adolescent Male With Pompe Disease and Thoracic Lordosis: A Case Report.
    A A Case Rep 2017 Oct;9(7):199-203
    From the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
    An adolescent male with late-onset Pompe disease (glycogen storage disease type II) presented with a history of restrictive airway disease and a near-cardiorespiratory arrest during anesthesia for a liver biopsy initially thought to be due to bronchospasm. During a subsequent posterior spinal fusion procedure, he suffered cardiorespiratory arrest resulting in the procedure being aborted. Bronchoscopy performed shortly after resuscitation revealed an undiagnosed narrowing of the distal trachea and bronchi. Read More

    Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe disease: A longitudinal follow-up.
    Mol Genet Metab 2017 Jun 1;121(2):127-137. Epub 2017 May 1.
    Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. Electronic address:
    This study examines the long-term cognitive and academic outcomes of 11 individuals with infantile onset Pompe disease (IOPD) (median age=11years, 1month, range=5years, 6months through 17years of age) treated with enzyme replacement therapy from an early age. All participants (7 males, 4 females) were administered individual intelligence tests (Wechsler or Leiter scales or both), a measure of their academic skill levels (Woodcock-Johnson Tests of Achievement), and a screening measure of visual-motor integration ability (Beery-Buktenica). Consistent with our earlier findings, median IQ scores for the entire group on the Wechsler (median=84) and Leiter (median=92) scales continue to fall at the lower end of the average range compared to same-aged peers. Read More

    European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience.
    Eur J Neurol 2017 06 6;24(6):768-e31. Epub 2017 May 6.
    Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany.
    Background And Purpose: Pompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in adult patients were developed and reported here.

    Methods: Three consensus meetings were organized through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. Read More

    Glycogen Synthesis in Glycogenin 1-Deficient Patients: A Role for Glycogenin 2 in Muscle.
    J Clin Endocrinol Metab 2017 Aug;102(8):2690-2700
    Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
    Context: Glycogen storage disease (GSD) type XV is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1-deficient patients, suggesting an alternative for glycogen buildup. A likely candidate is glycogenin 2, an isoform expressed in the liver and heart but not in healthy skeletal muscle. Read More

    Chest Wall Kinematics Using Triangular Cosserat Point Elements in Healthy and Neuromuscular Subjects.
    Ann Biomed Eng 2017 08 27;45(8):1963-1973. Epub 2017 Apr 27.
    Faculty of Mechanical Engineering, Technion Israel Institute of Technology, 32000, Haifa, Israel.
    Optoelectronic plethysmography (OEP) is a noninvasive method for assessing lung volume variations and the contributions of different anatomical compartments of the chest wall (CW) through measurements of the motion of markers attached to the CW surface. The present study proposes a new method for analyzing the local CW kinematics from OEP measurements based on the kinematics of triangular Cosserat point elements (TCPEs). 52 reflective markers were placed on the anterior CW to create a mesh of 78 triangles according to an anatomical model. Read More

    Mass Spectrometry but Not Fluorimetry Distinguishes Affected and Pseudodeficiency Patients in Newborn Screening for Pompe Disease.
    Clin Chem 2017 Jul 27;63(7):1271-1277. Epub 2017 Apr 27.
    Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA.
    Background: Deficiency of the lysosomal enzyme acid α-glucosidase (GAA) causes Pompe disease. Newborn screening for Pompe disease is ongoing, and improved methods for distinguishing affected patients from those with pseudodeficiency, especially in the Asian population, would substantially reduce the number of patient referrals for clinical follow-up.

    Methods: We measured the enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS) using a tandem mass spectrometry (MS/MS) assay. Read More

    E7 (1057ΔTA) mutation of the acidic α-glucosidase gene causes Pompe's disease in Droughtmaster cattle.
    Aust Vet J 2017 May;95(5):138-142
    The University of Queensland, Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, Rockhampton, QLD, Australia.
    Objective: To determine whether known loss-of-function alleles of the acidic α-glucosidase gene (GAA) are present in the Droughtmaster breed and, if so, whether the clinical signs and pathology of generalised glycogenosis (Pompe's disease) previously reported in other affected cattle are also seen in homozygous Droughtmasters.

    Design: Existing genomic and other diagnostic tests developed for generalised glycogenosis in cattle were used to test for the presence of the three known loss-of-function alleles of GAA in a herd of Droughtmaster cattle. Two calves with clinical signs of generalised glycogenosis were submitted for necropsy. Read More

    Investigation on acute effects of enzyme replacement therapy and influence of clinical severity on physiological variables related to exercise tolerance in patients with late onset Pompe disease.
    Neuromuscul Disord 2017 Jun 10;27(6):542-549. Epub 2017 Mar 10.
    Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
    Exercise intolerance is one of the clinical hallmarks of late-onset Pompe disease (LOPD). We studied the acute effects of ERT on the physiological variables associated with exercise tolerance in patients chronically ERT treated. Moreover, we assessed the influence of clinical severity on the investigated variables. Read More

    Targeted population screening of late onset Pompe disease in unspecified myopathy patients for Korean population.
    Neuromuscul Disord 2017 Jun 10;27(6):550-556. Epub 2017 Mar 10.
    Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:
    We performed targeted population screening of late onset Pompe disease (LOPD) in unspecified myopathy patients, because early diagnosis is difficult due to its heterogeneous clinical features. We prospectively enrolled 90 unrelated myopathic patients who had one or more signs out of five LOPD-like clinical findings (proximal weakness, axial weakness, lingual weakness, respiratory difficulty, idiopathic hyperCKemia). Acid alpha glucosidase activity was evaluated with dried blood spot and mixed leukocyte simultaneously. Read More

    Clinical and Molecular Characterization of Infantile-Onset Pompe Disease in Mainland Chinese Patients: Identification of Two Common Mutations.
    Genet Test Mol Biomarkers 2017 Jun 10;21(6):391-396. Epub 2017 Apr 10.
    1 Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine , Shanghai, China .
    Aims: We sought to understand the clinical course and molecular defects of infantile-onset Pompe disease (IOPD) among mainland Chinese patients.

    Materials And Methods: Twenty-five Chinese patients with IOPD were enrolled and clinical data were retrospectively reviewed. The entire coding region of the GAA gene was amplified by polymerase chain reaction and analyzed by direct sequencing. Read More

    Cutting Edge: Increased Autoimmunity Risk in Glycogen Storage Disease Type 1b Is Associated with a Reduced Engagement of Glycolysis in T Cells and an Impaired Regulatory T Cell Function.
    J Immunol 2017 05 7;198(10):3803-3808. Epub 2017 Apr 7.
    Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy;
    Glycogen storage disease type 1b (GSD-1b) is an autosomal-recessive disease caused by mutation of glucose-6-phosphate transporter and characterized by altered glycogen/glucose homeostasis. A higher frequency of autoimmune diseases has been observed in GSD-1b patients, but the molecular determinants leading to this phenomenon remain unknown. To address this question, we investigated the effect of glucose-6-phosphate transporter mutation on immune cell homeostasis and CD4T cell functions. Read More

    Respiratory manifestations in late-onset Pompe disease: a case series conducted in Brazil.
    J Bras Pneumol 2017 Jan-Feb;43(1):54-59
    . Centro de Genética Médica, Instituto Nacional de Saúde da Mulher, Criança e Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro (RJ) Brasil.
    Objective:: To describe respiratory function in a series of patients with late-onset Pompe disease after the definitive diagnosis and before enzyme replacement therapy.

    Methods:: This was a cross-sectional study involving patients with a definitive molecular diagnosis of late-onset Pompe disease. The data analyzed included age at symptom onset; age at definitive diagnosis; type of initial symptoms; time from symptom onset to diagnosis; FVC in the sitting and supine positions; six-minute walk distance; and locomotor ability. Read More

    Production of recombinant human acid α-glucosidase with high-mannose glycans in gnt1 rice for the treatment of Pompe disease.
    J Biotechnol 2017 May 29;249:42-50. Epub 2017 Mar 29.
    Department of Molecular Biology, Chonbuk National University, 664-14 Dukjindong, Jeonju, Jeollabuk-do 561-756, Republic of Korea; Department of Bioactive Material Science, Chonbuk National University, 664-14 Dukjindong, Jeonju, Jeollabuk-do 561-756, Republic of Korea; Research Center of Bioactive Materials, Chonbuk National University, 664-14 Dukjindong, Jeonju, Jeollabuk-do 561-756, Republic of Korea. Electronic address:
    Lysosomal storage diseases are a group of inherited metabolic disorders. Patients are treated with enzyme replacement therapy (ERT), in which the replacement enzymes are required to carry terminal mannose or mannose 6-phosphate residues to allow efficient uptake into target cells and tissues. N-acetylglucosaminyltransferase-I (GnTI) mediates N-glycosylation in the cis cisternae of the Golgi apparatus by adding N-acetylglucosamine to the exposed terminal mannose residue of core N-glycan structures for further processing. Read More

    Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction.
    Mol Ther Methods Clin Dev 2017 Mar 11;4:126-136. Epub 2017 Jan 11.
    Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
    Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10vector genomes [vg]/kg). Read More

    Duvoglustat HCl Increases Systemic and Tissue Exposure of Active Acid α-Glucosidase in Pompe Patients Co-administered with Alglucosidase α.
    Mol Ther 2017 May 22;25(5):1199-1208. Epub 2017 Mar 22.
    University of Florida, Gainesville, FL 32611, USA.
    Duvoglustat HCl (AT2220, 1-deoxynojirimycin) is an investigational pharmacological chaperone for the treatment of acid α-glucosidase (GAA) deficiency, which leads to the lysosomal storage disorder Pompe disease, which is characterized by progressive accumulation of lysosomal glycogen primarily in heart and skeletal muscles. The current standard of care is enzyme replacement therapy with recombinant human GAA (alglucosidase alfa [AA], Genzyme). Based on preclinical data, oral co-administration of duvoglustat HCl with AA increases exposure of active levels in plasma and skeletal muscles, leading to greater substrate reduction in muscle. Read More

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