scholarly journals Pompe disease, a storage cardiomyopathy

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Tiziana Felice
Keyword(s):  
Pompe Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Treatment Options ◽  
Premature Death ◽  
Glycogen Storage Disease Type ◽  
Lysosomal Storage ◽  
Respiratory Compromise ◽  
Enzyme Replacement ◽  
Geographical Regions

Pompe disease also known as glycogen storage disease type II, is a rare and progressive lysosomal storage disorder caused by the deficiency of the enzyme acid α-glucosidase. This results in the accumulation of glycogen in various tissues particularly involving the heart, skeletal muscle and liver. It is inherited in an autosomal recessive manner due to mutations in the GAA gene. There are several known pathogenic variants, some of which are particularly common in certain geographical regions. Pompe disease is a single disease exhibiting a heterogeneous clinical spectrum depending on the extent of enzyme deficiency, the age of onset, the progression of the disease and the degree of organ involvement. It may lead to muscle weakness, hypotonia, respiratory compromise and premature death. Pompe disease is classically divided into two forms, infantile and late-onset disease. The infantile form is further subdivided into classical and non-classical subtypes. Cardiac involvement is particularly seen in the infantile phenotype of the condition, presenting as severe cardiomyopathy associated with conduction abnormalities. Enzyme replacement therapy with recombinant human acid α-glucosidase is the approved treatment option for patients with this metabolic condition. Further research is currently being done to explore more treatment options. One must keep in mind other metabolic and mitochondrial conditions, which may give a similar cardiac and neurological clinical picture.

scholarly journals Rare Diseases in Neurology — Caring for a Patient with Pompe’s Disease

2019 ◽  
Vol 8 (4) ◽  
pp. 170-176
Author(s):  
Anna Roszmann ◽  
◽  
Mikołaj Hamerski ◽  
Marcelina Skrzypek-Czerko ◽  
◽  
...  
Keyword(s):  
Clinical Picture ◽  
Pompe Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease ◽  
Disease Case ◽  
Nurses Role

Introduction. Pompe disease, a severe metabolic myopathy, is caused by mutations in the gene coding for acid alphaglucosidase (GAA), what lead to intralysosomal accumulation of glycogen in all tissues, most notably in skeletal muscles. Pompe disease was the first documented lysosomal storage disease, nowadays we know around 60 similar disorders. Aim. Presentation of the clinical picture of a man with Pompe’s disease. Case Report. A man at the age of 40, diagnosis of the Pompe’s disease was made only at the age of 31. The first symptoms, indicating the patient’s development of the disease, were already present in the early school age. At first, the clinical picture presented by the patient led to the diagnosis of muscular dystrophy. Discussion. Pompe disease presents as a continuum of clinical phenotypes that differ by age of onset, severity, and organ involvement. Pompe disease affects people of all ages with varying degrees of severity. Two main broad types are recognized based on the onset of symptoms and the presence or absence of cardiomyopathy. Infantile onset Pompe disease (IOPD) as one, and the most severe for mod the disease. Other and less destructive is late-onset Pompe disease (LOPD) manifests any time after 12 months of age. The disease can be successfully treated by enzyme replacement therapy with alglucosidase alfa that was approved for human use in 2006. Conclusions. In big importance is nurses role as educators and support for the patients during their hospitalizations for medicine infusions twice a month. It time when the knowledge and significance of proper life style can be discussed and implemented to empower the patients. (JNNN 2019;8(4):170–176) Key Words: Pompe’s disease, treatment, diagnosis, care

scholarly journals Pompe Disease: New Developments in an Old Lysosomal Storage Disorder

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1339
Author(s):  
Naresh K. Meena ◽  
Nina Raben
Keyword(s):  
Pompe Disease ◽  
Specific Treatment ◽  
Lysosomal Storage Diseases ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Monogenic Diseases ◽  
Progressive Accumulation ◽  
Alpha Glucosidase

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. Both the success and limitations of ERT provided novel insights in the pathophysiology of the disease and motivated the scientific community to develop the next generation of therapies that have already progressed to the clinic.

Pompe Disease

2016 ◽  
Author(s):  
Ans T. van der Ploeg ◽  
Pascal Laforêt
Keyword(s):  
Pompe Disease ◽  
Late Onset ◽  
Data Gathering ◽  
Autosomal Recessive Disorder ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Walking Distance ◽  
Patient Registries ◽  
Enzyme Replacement ◽  
Progressive Muscle Weakness

Pompe disease, also named acid maltase deficiency and glycogen storage disease type II (GSDII), is a rare autosomal recessive disorder caused by the deficiency of the glycogen-degrading lysosomal enzyme acid α‎-glucosidase. The clinical spectrum of this disease is broad, varying from a lethal infantile-onset generalized myopathy including cardiomyopathy, to late-onset slowly progressive muscle weakness mimicking limb-girdle muscular dystrophy. Respiratory insufficiency is a frequent complication and the main cause of death. The prognosis of Pompe disease has changed considerably with the use of enzyme replacement therapy using recombinant acid α‎-glucosidase (alglucosidase alfa), which has been widely available since 2006. Improvements in survival and major motor achievements can be observed in patients with infantile forms, and recent studies demonstrate improvement of walking distance and stabilization of pulmonary function in late-onset forms. A longer-term study of the safety and efficacy of ERT, based on data gathering across the complete spectrum of Pompe disease via national or international patient registries, is needed in order to formulate more precise guidelines for treatment.

scholarly journals Liquid Chromatography–Tandem Mass Spectrometry Assay of Leukocyte Acid α-Glucosidase for Post-Newborn Screening Evaluation of Pompe Disease

2017 ◽  
Vol 63 (4) ◽  
pp. 842-851 ◽  
Author(s):  
Na Lin ◽  
Jingyu Huang ◽  
Sara Violante ◽  
Joseph J Orsini ◽  
Michele Caggana ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Pompe Disease ◽  
Late Onset ◽  
Treatment Options ◽  
Internal Standard ◽  
Lysosomal Storage ◽  
Blood Samples ◽  
Liquid Chromatography Tandem Mass ◽  
Progressive Weakness

Abstract 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. To date, no enzyme assay of acid α-glucosidase (GAA) has been described that can differentiate IOPD vs LOPD using blood samples. METHODS We incubated 10 μL leukocyte lysate and 25 μL GAA substrate and internal standard (IS) assay cocktail for 1 h. The reaction was purified by a liquid–liquid extraction. The extracts were evaporated and reconstituted in 200 μL methanol and analyzed by LC-MS/MS for GAA activity. RESULTS A 700-fold higher analytical range was observed with the LC-MS/MS assay compared to the fluorometric method. When GAA-null and GAA-containing fibroblast lysates were mixed, GAA activity could be measured accurately even in the range of 0%–1% of normal. The leukocyte GAA activity in IOPD (n = 4) and LOPD (n = 19) was 0.44–1.75 nmol · h−1 · mg−1 and 2.0–6.5 nmol · h−1 · mg−1, respectively, with no overlap. The GAA activity of pseudodeficiency patients ranged from 3.0–28.1 nmol · h−1 · mg−1, showing substantial but incomplete separation from the LOPD group. CONCLUSIONS This assay allows determination of low residual GAA activity in leukocytes. IOPD, LOPD, and pseudodeficiency patients can be partially differentiated by measuring GAA using blood samples.

scholarly journals Recomendações para o Diagnóstico da Forma Tardia da Doença de Pompe

2014 ◽  
Vol 27 (4) ◽  
pp. 525 ◽  
Author(s):  
Luís Brito-Avô ◽  
José Delgado Alves ◽  
João Matos Costa ◽  
Ana Valverde ◽  
Lélita Santos ◽  
...  
Keyword(s):  
Muscle Biopsy ◽  
Pompe Disease ◽  
Storage Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Neuromuscular Diseases ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Diagnostic Challenge

<strong>Introduction:</strong> Pompe disease is a progressive and debilitating autossomal recessive myopathy due to mutations in lysossomal acid-α-glucosidase. Its late-onset form has a heterogeneous presentation mimicking other neuromuscular diseases, leading to diagnostic challenge.<br /><strong>Objective:</strong> To develop consensus based recommendations for the diagnosis of late-onset Pompe Disease.<br /><strong>Material and Methods:</strong> Bibliographic review and analysis of an opinion questionnaire applied to a group of specialists with expertise in the diagnosis of several myopathies and lysossomal storage disorders. Discussed in consensus meeting.<br /><strong>Recommendations:</strong> Patients with a progressive limb-girdle weakness, fatigue, cramps and muscle pain should be evaluated with CK levels, electromyography, dynamic spirometry and muscle biopsy in inconclusive cases. Suspected cases and those in which muscle biopsy could not allow other diagnosis should be screened for lysossomal acid-α-glucosidase deficiency with DBS (dried blood spot). The diagnosis should be confirmed by determination of lysossomal acid-α-glucosidase activity in a second sample and lysossomal acid-α-glucosidase gene sequencing.<br /><strong>Keywords:</strong> Age of Onset; Consensus; Glycogen Storage Disease Type II.

112 Blood spot testing for late onset pompe disease

2018 ◽  
Vol 89 (6) ◽  
pp. A44.2-A44
Author(s):  
Julia Dobbins ◽  
Tim Pyragius ◽  
Kristian Brion ◽  
Sharon Chin ◽  
Melissa Gurner ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pompe Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Dried Blood Spot ◽  
Molecular Testing ◽  
Enzyme Replacement ◽  
Number Of Patients ◽  
Diagnosis Rate ◽  
Blood Spot

IntroductionPompe disease is classified by age of onset and presentation. Late-onset Pompe disease (LOPD) generally presents with progressive limb-girdle and respiratory muscle weakness. Diagnosis is confirmed following dried blood spot (DBS) enzyme assay by a second method, either mutation or glucose tetra-saccharide analysis.MethodsFrom 2000 to 2016, acid α –glucosidase (GAA) activity in DBS was measured using the immuno-capture assay of . Umapathysivam et al. (2001) From 2016 testing used the multiplex tandem mass spectrometry method (6-PLEX LC-MSMS, Perkin Elmer), measuring six lysosomal storage disease enzymes from one DBS. Glucose tetra-saccharides were measured by mass spectrometry and mutation analysis of the GAA gene was performed using either Sanger or Next Generation Sequencing, the latter confirmed by sequencing.ResultsBetween 2000 and 2016, approximately 1500 samples were screened for Pompe disease with 77 positives, a diagnosis rate of 5.1%. Of these, 33 were infantile Pompe disease, with 44 LOPD. Since May 2016, a further 850 patients have been screened for Pompe disease using the MSMS method and of these, 28 patients have screened as positive, with 19 confirmed as having Pompe disease, either by molecular testing or urine tetra-saccharide measurement, a diagnosis rate of 2.2%. Of these 19 patients, 17 are LOPD, with only two infants being diagnosed in this time. Seven adults are still to be confirmed by a second test.ConclusionThe number of patients presenting for testing follows the recent Australian government funding for enzyme replacement therapy for adults with LOPD. The ease of submitting a dried blood spot sample for testing has contributed to an increase in test requests, although this may also reflect an increased recognition of this condition. These patients may have already been diagnosed clinically, but in the absence of a treatment, there was little benefit in a formal diagnosis.

scholarly journals A Newborn with Infantile-Onset Pompe Disease Improving after Administration of Enzyme Replacement Therapy: Case Report

2020 ◽  
Author(s):  
Meltem Bor ◽  
Ozkan Ilhan ◽  
Evren Gumus ◽  
Solmaz Ozkan ◽  
Meryem Karaca
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Motor Development ◽  
Pompe Disease ◽  
Late Onset ◽  
Elevated Serum ◽  
Homozygous Mutation ◽  
Lysosomal Storage ◽  
Normal Value ◽  
Enzyme Replacement

AbstractPompe disease (PD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of acid α-1,4-glucosidase enzyme (GAA). PD has two forms, namely the infantile-onset and the late-onset form. In untreated cases, infantile-onset form usually leads to cardio-respiratory failure and death in the first year of life. Herein, we report a newborn with infantile-onset PD characterized by muscular hypotonia, respiratory distress, hypertrophic cardiomyopathy, hepatomegaly, elevated serum enzyme levels of aspartate aminotransferase of 117 IU/L (three times the normal value), alanine aminotransferase of 66 IU/L (1.8 times the normal value), lactate dehydrogenase of 558 IU/L (1.2 times the normal value), and creatine kinase >5,000 IU/L (16 times the normal value). Dried blood spot testing was performed and revealed decreased GAA enzymatic activity (0.07 nmol/mL/h, normal 0.93–7.33 nmol/mL/h). GAA gene analysis performed for confirming the diagnosis showed homozygous mutation c.896T >C (p.Leu299Pro). Initiation of enzyme replacement therapy (ERT) (ERT; 20 mg/kg, once every week) at 28 days of age resulted in weaning off from respiratory support within 1 week after treatment, normalization of cardiac abnormalities, and normal neuromotor development in the 16th month of age. Early diagnosis and early treatment with ERT, especially in the neonatal period, is of great importance to improve cardiac function and motor development in infantile-onset PD.

scholarly journals Homozygotic intronic GAA mutation in three siblings with late-onset Pompe's disease

2010 ◽  
Vol 68 (2) ◽  
pp. 194-197 ◽  
Author(s):  
Anderson Kuntz Grzesiuk ◽  
Sueli Mieko Oba Shinjo ◽  
Roseli da Silva ◽  
Marcela Machado ◽  
Marcial Francis Galera ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Age Of Onset ◽  
Late Onset ◽  
Activity Measurement ◽  
Respiratory Compromise ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease ◽  
C 32 ◽  
Gaa Gene

Pompe's disease (PD) is a metabolic myopathy caused by the accumulation of lysosomal glycogen, secondary to acid α-glucosidase (GAA) enzyme deficiency. Childhood and late-onset forms are described, differing by the age of onset and symptoms. In this study were analyzed affected siblings with Pompe's disease (PD) and their distinct clinical and pathological presentations. METHOD: Diagnosis was performed by the clinical presentation of limb-girdle dystrophies and respiratory compromise. Confirmatory diagnoses were conducted by muscle biopsy, GAA activity measurement and by GAA gene genotyping. RESULTS: The findings suggested muscular involvement due to GAA deficiency. GAA genotyping showed they are homozygous for the c.-32-3C>A mutation. CONCLUSION: Herein we reported a family where three out of five siblings were diagnosed with late-onset PD, although it is a rare metabolic disease inherited in an autossomal recessive manner. We emphasize the importance of including this presentation within the differential diagnoses of the limb-girdle dystrophies once enzyme replacement therapy is available.

scholarly journals Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex

2020 ◽  
Vol 21 (23) ◽  
pp. 9121
Author(s):  
Nataliya Yuskiv ◽  
Katsumi Higaki ◽  
Sylvia Stockler-Ipsiroglu
Keyword(s):  
Late Onset ◽  
Treatment Options ◽  
Joint Destruction ◽  
Cord Compression ◽  
Health Concern ◽  
Lysosomal Storage ◽  
Dysostosis Multiplex ◽  
Gm1 Gangliosidosis ◽  
Enzyme Replacement ◽  
Morquio A

Morquio B disease (MBD) is an autosomal recessive GLB1-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in GALNS-related Morquio A disease. MBD may present as pure skeletal phenotype (pure MBD) or in combination with the neuronopathic manifestations seen in type 2 (juvenile) or type 3 (late onset) GM1 gangliosidosis (MBD plus). The main skeletal features are progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly and odontoid hypoplasia. The main neuronopathic features are dystonia, ataxia, and intellectual/developmental/speech delay. Spinal cord compression occurs as a complication of spinal dysostosis. Chronic pain is reported, along with mobility issues and challenges with daily living and self-care activities, as the most common health concern. The most commonly reported orthopedic surgeries are hip and knee replacements. Keratan sulphate-derived oligosaccharides are characteristic biomarkers. Residual β-galactosidase activities measured against synthetic substrates do not correlate with the phenotype. W273 L and T500A are the most frequently observed GLB1 variants in MBD, W273L being invariably associated with pure MBD. Cytokines play a role in joint destruction and pain, providing a promising treatment target. In the future, patients may benefit from small molecule therapies, and gene and enzyme replacement therapies, which are currently being developed for GM1 gangliosidosis.

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