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    1706 results match your criteria Glycogen Storage Disease Type II Pompe Disease

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    Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation.
    Mol Genet Metab 2017 Dec 23. 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

    Aberrant proliferation and differentiation of glycogen storage disease type Ib mesenchymal stem cells.
    FEBS Lett 2017 Dec 14. Epub 2017 Dec 14.
    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 G6PT-/- hMSCs were established. G6PT-/- hMSCs 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

    Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy.
    Mol Genet Metab 2017 Oct 13. 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

    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.
    Objective: 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. Method: 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

    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

    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

    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 May 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 CD4+ T 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 × 1011 vector genomes [vg]/kg). Read More

    Airway smooth muscle dysfunction in Pompe (Gaa-/- ) mice.
    Am J Physiol Lung Cell Mol Physiol 2017 Jun 23;312(6):L873-L881. Epub 2017 Mar 23.
    Division of Pulmonary Medicine, Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts;
    Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase (GAA), an enzyme responsible for hydrolyzing lysosomal glycogen. Deficiency of GAA leads to systemic glycogen accumulation in the lysosomes of skeletal muscle, motor neurons, and smooth muscle. Skeletal muscle and motor neuron pathology are known to contribute to respiratory insufficiency in Pompe disease, but the role of airway pathology has not been evaluated. Read More

    Alglucosidase alfa therapy for Pompe disease in pregnancy - Case report.
    J Neurol Sci 2017 Apr 26;375:167-169. Epub 2017 Jan 26.
    Department of Neurology, COPERNICUS Podmiot Leczniczy Sp. z o.o. Szpital św. Wojciecha, Al. Jana Pawła II 50, 80-462 Gdańsk, Poland; Department of Neurological and Psychiatric Nursing, Medical University of Gdańsk, ul. Dębinki 7, 80-952 Gdańsk, Poland.

    Cardiac response to enzyme replacement therapy in infantile Pompe disease with severe hypertrophic cardiomyopathy.
    Echocardiography 2017 Apr 7;34(4):621-624. Epub 2017 Mar 7.
    Department of Pediatrics (Cardiology), Louisiana State University Health Sciences Center, New Orleans, LA, USA.
    Classic infantile-onset Pompe disease (IOPD), characterized by predominantly cardiac involvement, used to be considered uniformly lethal within months. The availability of enzyme replacement therapy (ERT) has transformed the course of the disease. Decrease in ventricular hypertrophy and improvement in ventricular function have been suggested as proof for efficacy. Read More

    Cardiac manifestations of inherited metabolic disease in children.
    Pediatr Int 2017 May;59(5):525-529
    Department of Congenital Heart Disease, Evelina Children's Hospital, London, UK.
    Inborn errors of metabolism (IEM) are responsible for around 5% of all cases of cardiomyopathy (CM) and for 15% of non-idiopathic cases. Storage disorders such as Pompe disease (glycogen storage disease type II) typically cause hypertrophic CM, whereas the accumulation of toxic metabolites, as seen in the organic acidurias, is associated with dilated cardiomyopathy (DCM). Mixed pathology is also possible, particularly in late presentations. Read More

    Human-Induced Pluripotent Stem Cell-Based Modeling of Cardiac Storage Disorders.
    Curr Cardiol Rep 2017 Mar;19(3):26
    Department of Medicine, Division of Cardiology, University of California San Diego, 9500 Gilman Drive, Biomedical Research Facility, Room 1217 AA, La Jolla, CA, 92093, USA.
    Purpose Of Review: The aim of this study is to review the published human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models of cardiac storage disorders and to evaluate the limitations and future applications of this technology.

    Recent Findings: Several cardiac storage disorders (CSDs) have been modeled using patient-specific hiPSC-CMs, including Anderson-Fabry disease, Danon disease, and Pompe disease. These models have shown that patient-specific hiPSC-CMs faithfully recapitulate key phenotypic features of CSDs and respond predictably to pharmacologic manipulation. Read More

    Diagnostic needs for rare diseases and shared prediagnostic phenomena: Results of a German-wide expert Delphi survey.
    PLoS One 2017 24;12(2):e0172532. Epub 2017 Feb 24.
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Hannover, Germany.
    Background: Worldwide approximately 7,000 rare diseases have been identified. Accordingly, 4 million individuals live with a rare disease in Germany. The mean time to diagnosis is about 6 years and patients receive several incorrect diagnoses during this time. Read More

    Liquid Chromatography-Tandem Mass Spectrometry Assay of Leukocyte Acid α-Glucosidase for Post-Newborn Screening Evaluation of Pompe Disease.
    Clin Chem 2017 Apr 14;63(4):842-851. Epub 2017 Feb 14.
    Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY;
    Background: Pompe disease (PD) is the first lysosomal storage disorder to be added to the Recommended Uniform Screening Panel for newborn screening. This condition has a broad phenotypic spectrum, ranging from an infantile form (IOPD), with severe morbidity and mortality in infancy, to a late-onset form (LOPD) with variable onset and progressive weakness and respiratory failure. Because the prognosis and treatment options are different for IOPD and LOPD, it is important to accurately determine an individual's phenotype. Read More

    The emerging phenotype of late-onset Pompe disease: A systematic literature review.
    Mol Genet Metab 2017 Mar 11;120(3):163-172. Epub 2016 Dec 11.
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. Electronic address:
    Background: Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal glycogen-hydrolyzing enzyme acid α-glucosidase (GAA). The adult-onset form, late-onset Pompe disease (LOPD), has been characterized by glycogen accumulation primarily in skeletal, cardiac, and smooth muscles, causing weakness of the proximal limb girdle and respiratory muscles. However, increased scientific study of LOPD continues to enhance understanding of an evolving phenotype. Read More

    A Conversation with Kurt and Rochelle Hirschhorn.
    Annu Rev Genomics Hum Genet 2017 Aug 26;18:31-44. Epub 2017 Jan 26.
    Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142; email:
    In this interview, Kurt and Rochelle Hirschhorn talk with their son, Joel, about their research and collaborations, the early years of medical genetics, the development of genetic counseling, the challenges of being a woman in science, and new challenges and directions for the study of human genetics. Read More

    Modulation of mTOR signaling as a strategy for the treatment of Pompe disease.
    EMBO Mol Med 2017 Mar;9(3):353-370
    Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
    Mechanistic target of rapamycin (mTOR) coordinates biosynthetic and catabolic processes in response to multiple extracellular and intracellular signals including growth factors and nutrients. This serine/threonine kinase has long been known as a critical regulator of muscle mass. The recent finding that the decision regarding its activation/inactivation takes place at the lysosome undeniably brings mTOR into the field of lysosomal storage diseases. Read More

    Autophagy dysregulation in Danon disease.
    Cell Death Dis 2017 Jan 19;8(1):e2565. Epub 2017 Jan 19.
    Venetian Institute of Molecular Medicine, Padova, Italy.
    The autophagy-lysosome system is critical for muscle homeostasis and defects in lysosomal function result in a number of inherited muscle diseases, generally referred to as autophagic vacuolar myopathies (AVMs). Among them, Danon Disease (DD) and glycogen storage disease type II (GSDII) are due to primary lysosomal protein defects. DD is characterized by mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. Read More

    Disruption of the gaa Gene in Zebrafish Fails to Generate the Phenotype of Classical Pompe Disease.
    DNA Cell Biol 2017 Jan;36(1):10-17
    1 Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University , Shanghai, China .
    The underlying pathogenic lesions of glycogen storage disease type II (GSD II) and the diversity of this disease among different species are still under exploration. Thus, we created an acid alpha-glucosidase (gaa) gene-mutated zebrafish model of GSD II and examined the sequential pathogenic changes. gaa mRNA and protein expression, enzymatic activity, and lysosomal glycogen accumulation were assessed, and the phenotypic changes were compared between wild-type (WT) and gaa-mutated zebrafish. Read More

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