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
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
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
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
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
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
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
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
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
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
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
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
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
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 × 10(11) vector genomes [vg]/kg). Read More
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
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.
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
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
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
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
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
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
Pompe disease is a glycogen storage disease caused by acid alfa-glucosidase deficiency. Here, we report clinical properties, genetic features of our late-onset Pompe patients. Seven patients were followed during the last 10 years in our institute. Read More
The effects of enzyme replacement therapy (ERT) in infantile Pompe disease are variable, necessitating the identification of biomarkers to assess the severity of disease and response to ERT. The aims of this study were to investigate whether quantification of muscle pathology in infantile Pompe disease prior to and during ERT is feasible at the light microscope, and to develop a score that summarizes the degree of muscle pathology in a comprehensive manner from PAS-stained resin sections alone. We, therefore, determined glycogen load, extent of muscle fibre disruption, and amount of autophagic vacuoles in resin-embedded muscle biopsy specimens from 11 infantile Pompe patients and 2 with early childhood phenotype by quantitative methods, correlated the findings with ultrastructural analyses, compared PAS-stained resin sections with conventional PAS-stained cryosections, and related the quantified degree of muscle damage from infantile patients to the effects of ERT. Read More
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Introduction: Late-onset Pompe disease (LOPD) is a rare disorder characterized by progressive proximal muscle weakness and early respiratory insufficiency, for which enzyme replacement therapy (ERT) is available.
Methods: Having diagnosed a case of LOPD presenting with bent spine syndrome, we conducted a brief survey in the French centers involved in management of Pompe disease, from which we collected data on 3 other cases.
Results: The patients (3 women and 1 man) had a mean age of 64 years (range 51-77 years) and a delay in diagnosis of approximately 10 years (range 8-42 years). Read More
Pompe disease is a rare neuromuscular disorder caused by an acid α-glucosidase (GAA) deficiency resulting in glycogen accumulation in muscle, leading to myopathy and respiratory weakness. Reveglucosidase alfa (BMN 701) is an insulin-like growth factor 2-tagged recombinant human acid GAA (rhGAA) that enhances rhGAA cellular uptake via a glycosylation-independent insulin-like growth factor 2 binding region of the cation-independent mannose-6-phosphate receptor (CI-MPR). The studies presented here evaluated the effects of Reveglucosidase alfa treatment on glycogen clearance in muscle relative to rhGAA, as well as changes in respiratory function and glycogen clearance in respiratory-related tissue in a Pompe mouse model (GAA(tm1Rabn)/J). Read More
Neuromuscular disorders such as Pompe disease (glycogen storage disease, type II), result in early and potentially irreversible cellular damage with a very limited opportunity for intervention in the newborn period. Pompe disease is due to deficiency in acid α-glucosidase (GAA) leading to lysosomal accumulation of glycogen in all cell types, abnormal myofibrillogenesis, respiratory insufficiency, neurological deficits, and reduced contractile function in striated muscle. Previous studies have shown that fetal delivery of recombinant adeno-associated virus (rAAV) encoding GAA to the peritoneal cavity of Gaa(-/-) mice resulted in high-level transduction of the diaphragm. Read More
Objective: To evaluate the effect of enzyme replacement therapy (ERT) on glycogen storage disease typeⅡ(GSDⅡ). Method: The clinical data of three juvenile onset and two infant onset GSDⅡpatients were collected from First Affiliated Hospital of Sun Yat-sen University in October 2015 to July 2016.Patient 1 was female, the age of onset was 15 months. Read More
Introduction: The clinical and histological presentations of the adult form of Pompe disease may be atypical. In such cases, identifying histological signs that point to the diagnosis would be crucial to avoid a delay in care. The aim of our study was to investigate the presence of rimmed vacuoles and acid phosphatase positivity in muscle biopsies of patients with late-onset Pompe disease. Read More
Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Read More
Objectives: Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far. Read More
The current study characterizes a cohort of limb-girdle muscular dystrophy (LGMD) in the United States using whole-exome sequencing. Fifty-five families affected by LGMD were recruited using an institutionally approved protocol. Exome sequencing was performed on probands and selected parental samples. Read More
Biochem Biophys Res Commun 2016 Oct 28;479(4):721-727. Epub 2016 Sep 28.
Mechanisms in Cell Biology and Diseases Research Group, School of Pharmacy and Medical Science, Division of Health Sciences, University of South Australia, Adelaide 5001, Australia. Electronic address:
Pompe disease is caused by a deficiency in the lysosomal enzyme α-glucosidase, and this leads to glycogen accumulation in the autolysosomes of patient cells. Glycogen storage material is exocytosed at a basal rate in cultured Pompe cells, with one study showing up to 80% is released under specific culture conditions. Critically, exocytosis induction may reduce glycogen storage in Pompe patients, providing the basis for a therapeutic strategy whereby stored glycogen is redirected to an extracellular location and subsequently degraded by circulating amylases. Read More
Introduction: The aim of this study was to evaluate the muscle MRI pattern of 9 patients (median age: 6.5 ± 2.74 years) affected by classic infantile-onset Pompe disease who were treated with enzyme replacement therapy. Read More
Introduction: Pompe disease is characterized by absence or deficiency of acid α-glucosidase, and several causative mutations are known. In this study we report clinical and laboratory data in Iranian patients with late-onset Pompe disease (LOPD), focusing on population-specific mutations.
Methods: Clinical and laboratory data of 14 patients from 10 families with the diagnosis of LOPD were recorded. Read More
A 72-year-old, seemingly healthy, Japanese man suddenly lost consciousness. At the emergency room, the patient's Glasgow coma scale score was 10 and a thoracic breathing pattern was observed. An arterial blood gas analysis indicated acute hypercarbic respiratory failure. Read More
Pregnancy and delivery are challenging in women affected by Pompe disease with respiratory involvement. We describe a 28-year-old woman, who continued to receive enzyme replacement therapy during pregnancy and had an uneventful vaginal birth. Before pregnancy the patient's vital capacity was 52% in sitting position and 51% in supine position. Read More
Pompe disease is an inherited disorder due to a mutation in the gene that encodes acid α-glucosidase (GAA). Children with infantile-onset Pompe disease develop progressive hypotonic weakness and cardiopulmonary insufficiency that may eventually require mechanical ventilation (MV). Our team conducted a first in human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory neural dysfunction in infantile-onset Pompe. Read More
Background: Diaphragm weakness is the main reason for respiratory dysfunction in patients with Pompe disease, a progressive metabolic myopathy affecting respiratory and limb-girdle muscles. Since respiratory failure is the major cause of death among adult patients, early identification of respiratory muscle involvement is necessary to initiate treatment in time and possibly prevent irreversible damage. In this paper we investigate the suitability of dynamic MR imaging in combination with state-of-the-art image analysis methods to assess respiratory muscle weakness. Read More
Aim: Glycogen storage disease type II (GSD II or Pompe disease; OMIM; 232 300) is a rare autosomal recessive lysosomal storage disorder resulting from deficiency of α-glucosidase and accumulation of glycogen in muscle. Clinical symptoms include weakness of skeletal and respiratory muscles and, in infants, cardiomyopathy. Patients with GSD II receive infusions of recombinant α-glucosidase (enzyme replacement therapy; ERT), which slow the progression of the disease. Read More
A number of studies have assessed the efficacy of alglucosidase alfa as an enzyme replacement therapy (ERT) on motor and respiratory endpoints in patients with late-onset Pompe disease (LOPD). A previous review evaluated the clinical efficacy and safety of alglucosidase alfa; however, it is difficult to draw inferences from individual studies due to small patient populations, particularly in evaluating the benefit on survival. To evaluate the current evidence on the long-term efficacy of alglucosidase alfa with regard to survival, motor, and respiratory function in patients with LOPD in relation to the natural progression of the disease, a new systematic literature review was performed identifying studies that assessed either mortality, percent predicted forced vital capacity (% FVC), or the 6-min walk test (6MWT) among treated and untreated LOPD patients. Read More
Pompe disease (glycogen storage disease type II (GSD-II)) is a myopathy caused by a genetic deficiency of acid α-glucosidase (GAA) leading to lysosomal glycogen accumulation causing muscle weakness, respiratory insufficiency and death. We previously demonstrated in GSD-II mice that a single injection of a helper-dependent adenovirus (HD-Ad) expressing GAA resulted in at least 300 days of liver secretion of GAA, correction of the glycogen storage in cardiac and skeletal muscles and improved muscle strength. Recent reports suggest that gene therapy modeling for lysososomal storage diseases in mice fails to predict outcomes in larger animal models. Read More
Deficiency of glycogen branching enzyme in glycogen storage disease type IV (GSD IV) results in accumulation of less-branched and poorly soluble polysaccharides (polyglucosan bodies) in multiple tissues. Standard enzymatic method, when used to quantify glycogen content in GSD IV tissues, causes significant loss of the polysaccharides during preparation of tissue lysates. We report a modified method including an extra boiling step to dissolve the insoluble glycogen, ultimately preserving the glycogen content in tissue homogenates from GSD IV mice. Read More
McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated. In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Read More