497 results match your criteria Acid Maltase Deficiency Myopathy

Novel autophagic vacuolar myopathies: Phenotype and genotype features.

Neuropathol Appl Neurobiol 2021 Jan 4. Epub 2021 Jan 4.

Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Autophagic vacuolar myopathies (AVMs) are an emerging group of heterogeneous myopathies sharing histopathological features on muscle pathology, in which autophagic vacuoles are the pathognomonic morphologic hallmarks. Glycogen storage disease type II (GSDII) caused by lysosomal acid α-glucosidase (GAA) deficiency is the best-characterised AVM.

Aims: This study aimed to investigate the mutational profiling of seven neuromuscular outpatients sharing clinical, myopathological and biochemical findings with AVMs. Read More

View Article and Full-Text PDF
January 2021

Respiratory failure and sleep-disordered breathing in late-onset Pompe disease: a narrative review.

J Thorac Dis 2020 Oct;12(Suppl 2):S235-S247

Lane Fox Respiratory Service, St. Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Late-onset Pompe disease (LOPD) is a rare autosomal recessive glycogen storage disease that results in accumulation of glycogen in muscle cells causing muscular weakness. It causes a progressive proximal myopathy, accompanied by respiratory muscle weakness, which can lead to ventilatory failure. In untreated LOPD, the most common cause of death is respiratory failure. Read More

View Article and Full-Text PDF
October 2020

[Pompe disease treated with enzyme replacement therapy in pregnancy].

Ideggyogy Sz 2020 Sep;73(9-10):339-344

Semmelweis Egyetem, Genomikai Medicina és Ritka Betegségek Intézete Budapest.

Pompe disease is a rare lysosomal storage disease inherited in a recessive manner resulting muscular dystrophy. Due to the lack of the enzyme alpha glucosidase, glycogen accumulates in the cells. In the infantile form of Pompe disease hypotonia and severe cardio-respiratory failure are common leading to death within 2 years if left untreated, while the late-onset form is characterized with limb-girdle and axial muscle weakness accompanied with respiratory dysfunction. Read More

View Article and Full-Text PDF
September 2020

Pompe Disease: New Developments in an Old Lysosomal Storage Disorder.

Biomolecules 2020 09 18;10(9). Epub 2020 Sep 18.

Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.

Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to severe cardiac and skeletal muscle myopathy due to progressive accumulation of glycogen. The discovery that acid alpha-glucosidase resides in the lysosome gave rise to the concept of lysosomal storage diseases, and Pompe disease became the first among many monogenic diseases caused by loss of lysosomal enzyme activities. The only disease-specific treatment available for Pompe disease patients is enzyme replacement therapy (ERT) which aims to halt the natural course of the illness. Read More

View Article and Full-Text PDF
September 2020

Distal muscle weakness is a common and early feature in long-term enzyme-treated classic infantile Pompe patients.

Orphanet J Rare Dis 2020 09 14;15(1):247. Epub 2020 Sep 14.

Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center, P.O. Box 2060, Rotterdam, 3000, CB, The Netherlands.

Background: Enzyme replacement therapy (ERT; alglucosidase alfa) has improved the prospects for patients with classic infantile Pompe disease considerably. However, over time we noticed that many of these children exhibit distal muscle weakness at an early age, which is in contrast to the primarily proximal and axial muscle weakness in patients with late-onset Pompe disease. This was reason to study the prevalence and severity of distal muscle weakness, and the sequence of muscle involvement over time in patients that had learned to walk under ERT. Read More

View Article and Full-Text PDF
September 2020

CRISPR-Cas9 generated Pompe knock-in murine model exhibits early-onset hypertrophic cardiomyopathy and skeletal muscle weakness.

Sci Rep 2020 06 25;10(1):10321. Epub 2020 Jun 25.

Department of Pediatrics, University of California-Irvine School of Medicine, Irvine, CA, 92697, USA.

Infantile-onset Pompe Disease (IOPD), caused by mutations in lysosomal acid alpha-glucosidase (Gaa), manifests rapidly progressive fatal cardiac and skeletal myopathy incompletely attenuated by synthetic GAA intravenous infusions. The currently available murine model does not fully simulate human IOPD, displaying skeletal myopathy with late-onset hypertrophic cardiomyopathy. Bearing a Cre-LoxP induced exonic disruption of the murine Gaa gene, this model is also not amenable to genome-editing based therapeutic approaches. Read More

View Article and Full-Text PDF

Myopathies with finger flexor weakness: Not only inclusion-body myositis.

Muscle Nerve 2020 10 1;62(4):445-454. Epub 2020 Jun 1.

Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota, 55905, USA.

Muscle disorders are characterized by differential involvement of various muscle groups. Among these, weakness predominantly affecting finger flexors is an uncommon pattern, most frequently found in sporadic inclusion-body myositis. This finding is particularly significant when the full range of histopathological findings of inclusion-body myositis is not found on muscle biopsy. Read More

View Article and Full-Text PDF
October 2020

Guidance for the care of neuromuscular patients during the COVID-19 pandemic outbreak from the French Rare Health Care for Neuromuscular Diseases Network.

Rev Neurol (Paris) 2020 Jun 20;176(6):507-515. Epub 2020 Apr 20.

Reference Center of Neuromuscular disorders and ALS, Timone University Hospital, AP-HM, 13385 Marseille, France; Medical Genetics, Aix-Marseille Université, Inserm UMR_1251, 13005 Marseille, France. Electronic address:

In France, the epidemic phase of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in February 2020 and resulted in the implementation of emergency measures and a degradation in the organization of neuromuscular reference centers. In this special context, the French Rare Health Care for Neuromuscular Diseases Network (FILNEMUS) has established guidance in an attempt to homogenize the management of neuromuscular (NM) patients within the French territory. Hospitalization should be reserved for emergencies, the conduct of treatments that cannot be postponed, check-ups for which the diagnostic delay may result in a loss of survival chance, and cardiorespiratory assessments for which the delay could be detrimental to the patient. Read More

View Article and Full-Text PDF

Dietary lipids in glycogen storage disease type III: A systematic literature study, case studies, and future recommendations.

J Inherit Metab Dis 2020 07 26;43(4):770-777. Epub 2020 Feb 26.

Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

A potential role of dietary lipids in the management of hepatic glycogen storage diseases (GSDs) has been proposed, but no consensus on management guidelines exists. The aim of this study was to describe current experiences with dietary lipid manipulations in hepatic GSD patients. An international study was set up to identify published and unpublished cases describing hepatic GSD patients with a dietary lipid manipulation. Read More

View Article and Full-Text PDF

Identification of two novel variants in GAA underlying infantile-onset Pompe disease in two Pakistani families.

J Pediatr Endocrinol Metab 2020 Apr;33(4):553-556

Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan.

Background Pompe disease (PD) is an autosomal recessive metabolic myopathy with an average incidence of one in 40,000 live births. It has a variable age of onset and can be diagnosed within the first 3 months. Heart involvement and muscle weakness are its primary manifestations. Read More

View Article and Full-Text PDF

Exercise therapy for muscle and lower motor neuron diseases.

Acta Myol 2019 Dec 1;38(4):215-232. Epub 2019 Dec 1.

Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.

Muscle and lower motor neuron diseases share a common denominator of perturbed muscle function, most often related to wasting and weakness of muscles. This leads to a number of challenges, such as restricted mobility and respiratory difficulties. Currently there is no cure for these diseases. Read More

View Article and Full-Text PDF
December 2019

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease.

Orphanet J Rare Dis 2020 01 13;15(1):11. Epub 2020 Jan 13.

Sanofi Genzyme, Cambridge, MA, USA.

Background: Limb-girdle muscular dystrophy (LGMD) is a group of neuromuscular disorders of heterogeneous genetic etiology with more than 30 directly related genes. LGMD is characterized by progressive muscle weakness involving the shoulder and pelvic girdles. An important differential diagnosis among patients presenting with proximal muscle weakness (PMW) is late-onset Pompe disease (LOPD), a rare neuromuscular glycogen storage disorder, which often presents with early respiratory insufficiency in addition to PMW. Read More

View Article and Full-Text PDF
January 2020

Glycogen storage in a zebrafish Pompe disease model is reduced by 3-BrPA treatment.

Biochim Biophys Acta Mol Basis Dis 2020 05 7;1866(5):165662. Epub 2020 Jan 7.

Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, 20133, Italy. Electronic address:

Pompe disease (PD) is an autosomal recessive muscular disorder caused by deficiency of the glycogen hydrolytic enzyme acid α-glucosidase (GAA). The enzyme replacement therapy, currently the only available therapy for PD patients, is efficacious in improving cardiomyopathy in the infantile form, but not equally effective in the late onset cases with involvement of skeletal muscle. Correction of the skeletal muscle phenotype has indeed been challenging, probably due to concomitant dysfunctional autophagy. Read More

View Article and Full-Text PDF

Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: a clinical study and review of the literature.

Genet Med 2020 05 6;22(5):898-907. Epub 2020 Jan 6.

Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.

Purpose: Enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) at standard dose of 20 mg/kg every other week is insufficient to halt the long-term progression of myopathy in Pompe disease.

Methods: We conducted a retrospective study on infantile-onset Pompe disease (IPD) and late-onset Pompe disease (LOPD) patients with onset before age 5 years, ≥12 months of treatment with standard dose ERT, and rhGAA immunogenic tolerance prior to dose escalation. Long-term follow-up of up to 18 years was obtained. Read More

View Article and Full-Text PDF

Adapted physical activity and therapeutic exercise in late-onset Pompe disease (LOPD): a two-step rehabilitative approach.

Neurol Sci 2020 Apr 7;41(4):859-868. Epub 2019 Dec 7.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Aerobic exercise, training to sustain motor ability, and respiratory rehabilitation may improve general functioning and quality of life (QoL) in neuromuscular disorders. Patients with late-onset Pompe disease (LOPD) typically show progressive muscle weakness, respiratory dysfunction and minor cardiac involvement. Characteristics and modalities of motor and respiratory rehabilitation in LOPD are not well defined and specific guidelines are lacking. Read More

View Article and Full-Text PDF

Clinical features of Pompe disease with motor neuronopathy.

Neuromuscul Disord 2019 11 25;29(11):903-906. Epub 2019 Sep 25.

Department of Medical Genetics, National Taiwan University Hospital, Room 19005, 19F, Children's Hospital Building, 8 Chung-Shan South Road, Taipei 10041, Taiwan; Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

Pathological studies on rodent models and patients with Pompe disease have demonstrated the accumulation of glycogen in spinal motor neurons; however, this finding has rarely been evaluated clinically in patients with Pompe disease. In this study, we analyzed seven patients (age, 7-11 years) with Pompe disease who received long-term enzyme replacement therapy. In addition to traditional myopathy-related clinical and electrophysiological features, these patients often developed bilateral foot drop, distal predominant weakness of four limbs, and hypo- or areflexia with preserved sensory function. Read More

View Article and Full-Text PDF
November 2019

Evaluation of antihypertensive drugs in combination with enzyme replacement therapy in mice with Pompe disease.

Mol Genet Metab 2020 02 17;129(2):73-79. Epub 2019 Oct 17.

Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States of America; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, United States of America. Electronic address:

Pompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA) leading to progressive myopathy. Enzyme replacement therapy (ERT) with recombinant human (rh) GAA has limitations, including inefficient uptake of rhGAA in skeletal muscle linked to low cation-independent mannose-6-phosphate receptor (CI-MPR) expression.

Purpose: To test the hypothesis that antihypertensive agents causing muscle hypertrophy by increasing insulin-like growth factor 1 expression can increase CI-MPR-mediated uptake of recombinant enzyme with therapeutic effects in skeletal muscle. Read More

View Article and Full-Text PDF
February 2020

Large variation in effects during 10 years of enzyme therapy in adults with Pompe disease.

Neurology 2019 11 16;93(19):e1756-e1767. Epub 2019 Oct 16.

From the Departments of Neurology (L.H., E.B., P.A.v.D., N.A.M.E.v.d.B.) and Pediatrics (M.E.K., A.T.v.d.P.), Center for Lysosomal and Metabolic Diseases Erasmus MC, and Department of Biostatistics (D.R.), University Medical Center Rotterdam, Netherlands; Institute of Myology (J.-Y.H., B.P., N.T., A.C.), Pitié-Salpêtrière Hospital, Paris; Department of Neurology (P.L.), Nord/Est/Ile de France Neuromuscular Center, Raymond Poincaré Teaching Hospital, AP-HP, Garches; and INSERM U1179 (P.L.), END-ICAP, Université Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.

Objective: To determine the effects of 10 years of enzyme replacement therapy (ERT) in adult patients with Pompe disease, focusing on individual variability in treatment response.

Methods: In this prospective, multicenter cohort study, we studied 30 patients from the Netherlands and France who had started ERT during the only randomized placebo-controlled clinical trial with ERT in late-onset Pompe disease (NCT00158600) or its extension (NCT00455195) in 2005 to 2008. Main outcomes were walking ability (6-minute walk test [6MWT]), muscle strength (manual muscle testing using Medical Research Council [MRC] grading), and pulmonary function (forced vital capacity [FVC] in the upright and supine positions), assessed at 3- to 6-month intervals before and after the start of ERT. Read More

View Article and Full-Text PDF
November 2019

The nature of respiratory muscle weakness in patients with late-onset Pompe disease.

Neuromuscul Disord 2019 08 22;29(8):618-627. Epub 2019 Jun 22.

Respiratory Physiology Laboratory, Institute for Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. Electronic address:

Late-onset Pompe disease (LOPD) causes myopathy of skeletal and respiratory muscles, and phrenic nerve pathology putatively contributes to diaphragm weakness. The aim of this study was to investigate neural contributions to diaphragm dysfunction, usefulness of diaphragm ultrasound, and involvement of expiratory abdominal muscles in LOPD. Thirteen patients with LOPD (7 male, 51±17 years) and 13 age- and gender-matched controls underwent respiratory muscle strength testing, ultrasound evaluation of diaphragm excursion and thickness, cortical and cervical magnetic stimulation (MS) of the diaphragm with simultaneous recording of surface electromyogram and twitch transdiaphragmatic pressure (twPdi; n = 6), and MS of the abdominal muscles with recording of twitch gastric pressure (twPgas; n = 6). Read More

View Article and Full-Text PDF

Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study.

J Clin Pathol 2019 Dec 15;72(12):805-809. Epub 2019 Jul 15.

Metabolic Medicine/Chemical Pathology, Guy's & St Thomas' Hospitals, London, UK

Aims: Adult-onset inherited errors of metabolism can be difficult to diagnose. Some cases of potentially treatable myopathy are caused by autosomal recessive acid α-1,4 glucosidase (acid maltase) deficiency (Pompé disease). This study investigated whether screening of asymptomatic patients with elevated creatine kinase (CK) could improve detection of Pompé disease. Read More

View Article and Full-Text PDF
December 2019

Bright tongue sign in patients with late-onset Pompe disease.

J Neurol 2019 Oct 29;266(10):2518-2523. Epub 2019 Jun 29.

Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA.

Background: Late-onset Pompe disease (LOPD) is an often misdiagnosed inherited myopathy for which treatment exists. We noticed a bright tongue sign on brain MRIs of two patients who were admitted to the ICU for respiratory failure of unclear origin, and who were eventually diagnosed with LOPD. This led us to systematically review brain MRIs of patients with LOPD and various other neuromuscular disorders (NMD). Read More

View Article and Full-Text PDF
October 2019

Spanish Pompe registry: Baseline characteristics of first 49 patients with adult onset of Pompe disease.

Med Clin (Barc) 2020 02 26;154(3):80-85. Epub 2019 Jun 26.

Unidad de Patología Neuromuscular, Departamento de Neurología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER). Electronic address:

Introduction And Objectives: Pompe disease is a rare autosomal recessive disorder produced by a deficiency of acid maltase. This deficit produces an accumulation of glycogen in tissues. Clinically it is mainly characterized by limb girdle and respiratory muscle weakness. Read More

View Article and Full-Text PDF
February 2020

Screening for late-onset Pompe disease in Poland.

Acta Neurol Scand 2019 Oct 18;140(4):239-243. Epub 2019 Jun 18.

Department of Neurology, Medical University of Warsaw, Warsaw, Poland.

Objectives: We aimed to screen for late-onset Pompe disease using the dried blood spot (DBS) test in a cohort of patients with limb-girdle muscle weakness or persistent hyperCKemia.

Materials And Methods: Patients with limb-girdle muscle weakness, persistently elevated CK, rigid spine syndrome, dyspnoea, myalgia or sibling of the patient diagnosed with LOPD were included in the study. Acid α-glucosidase (GAA) activity was measured on DBS by tandem mass spectrometry and followed by genetic testing when required. Read More

View Article and Full-Text PDF
October 2019

Comparison of recent pivotal recommendations for the diagnosis and treatment of late-onset Pompe disease using diagnostic nodes-the Pompe disease burden scale.

J Neurol 2019 Aug 18;266(8):2010-2017. Epub 2019 May 18.

Department of Radiation Oncology, Cantonal Hospital, 9007, St. Gallen, Switzerland.

Pompe disease is a rare autosomal-recessive disorder characterised by limb-girdle myopathy and respiratory weakness in the late-onset form (LOPD). Various mutations in the acid alpha-glucosidase gene lead to toxic lysosomal and extra-lysosomal glycogen accumulation in all organs due to ineffective glycogen clearance by the encoded enzyme. Only one randomized trial demonstrated beneficial effects of respiratory function and meters walked in the 6-min walking test with enzyme replacement therapy (ERT). Read More

View Article and Full-Text PDF

Severe distal muscle involvement and mild sensory neuropathy in a boy with infantile onset Pompe disease treated with enzyme replacement therapy for 6 years.

Neuromuscul Disord 2019 06 14;29(6):477-482. Epub 2019 Mar 14.

Department of Child Neurology, Justus Liebig University Giessen, 35392 Giessen, Germany.

Enzyme replacement therapy in infantile onset Pompe disease has led to a new phenotype with features not known in the pre-enzyme replacement therapy era. We investigated the origin of a rapidly emerging and severe weakness of the foot dorsiflexors in a 7-year-old boy after 6.5 years of enzyme replacement therapy. Read More

View Article and Full-Text PDF

Activated mTOR signaling pathway in myofibers with inherited metabolic defect might be an evidence for mTOR inhibition therapies.

Chin Med J (Engl) 2019 Apr;132(7):805-810

Institute of Neuromuscular and Neurodegenerative Diseases.

Background: Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles. Read More

View Article and Full-Text PDF

Selective screening of late-onset Pompe disease (LOPD) in patients with non-diagnostic muscle biopsies.

J Clin Pathol 2019 Jul 16;72(7):468-472. Epub 2019 Mar 16.

Division of Neurology, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Aims: As of 2016, there were five patients with Pompe in Slovenia (two infantile, one childhood and two adult onset) with a prevalence of 1:400 000; however, the prevalence of late-onset Pompe disease (LOPD) in some other countries means this ratio could be an underestimate. Since an LOPD muscle biopsy could be unspecific or even normal, the purpose of this study is to assess the prevalence of LOPD in patients with non-diagnostic muscle biopsies.

Methods: Six hundred biopsies were recorded at the Neuromuscular Tissue Bank of the University of Ljubljana for the period 2004-2014. Read More

View Article and Full-Text PDF

Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 2: diseases of motor neuron and skeletal muscle.

Neurol Sci 2019 Apr 25;40(4):671-681. Epub 2019 Feb 25.

Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

This is the second part of a two-part document intended to discuss recent therapeutic progresses in genetic neuromuscular disorders. The present review is for diseases of motor neuron and skeletal muscle, some of which reached recently the most innovative therapeutic approaches. Nusinersen, an SMN2 mRNA splicing modifier, was approved as first-ever therapy of spinal muscular atrophy (SMA) by FDA in 2016 and by EMA in 2017. Read More

View Article and Full-Text PDF

Desensitization of two young patients with infantile-onset Pompe disease and severe reactions to alglucosidase alfa.

Neurol Sci 2019 Jul 18;40(7):1453-1455. Epub 2019 Feb 18.

Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Via S. Pansini 5, Naples, Italy.

Pompe disease is a metabolic myopathy, due to deficiency of alpha glucosidase, with a wide clinical spectrum. Enzyme replacement therapy is the only available treatment to improve morbidity and mortality, especially in infantile-onset form. However, some patients experience infusion-associated reactions, which may restrict their access to this treatment. Read More

View Article and Full-Text PDF

PDGF-BB serum levels are decreased in adult onset Pompe patients.

Sci Rep 2019 02 14;9(1):2139. Epub 2019 Feb 14.

Neuromuscular Disorders Unit. Neurology Department Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona, Barcelona, Spain.

Adult onset Pompe disease is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzymatic replacement therapy with human recombinant alfa glucosidase. Motor functional tests and spirometry are commonly used to follow patients up. Read More

View Article and Full-Text PDF
February 2019