Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy.
ABSTRACT Pompe disease, or glycogen storage disease type II, is a rare autosomal recessive disorder caused by mutations in the gene that encodes for alpha-glucosidase. Presentation in infancy is associated with respiratory failure, cardiomyopathy, and severe muscle weakness. Juvenile- or adult-onset cases typically present with proximal muscle weakness and are associated with respiratory insufficiency or exertional dyspnea. Treatment, until recently, was focused on supportive measures, and infants diagnosed with Pompe disease usually died within the first year of life. The recent development of recombinant alpha-glucosidase has dramatically improved the life expectancy and quality of life of infantile-onset disease with improvements in respiratory and motor function observed in juvenile- or adult-onset cases. This review focuses on the presentation, pathogenesis, diagnosis, and treatment recommendations for Pompe disease in this new era of enzyme replacement therapy.
SourceAvailable from: Hernan Amartino[Show abstract] [Hide abstract]
ABSTRACT: Introduction Pompe disease (PD) is a rare autosomal recessive metabolic disorder which is caused by the absence or deficiency of the acid alpha-glucosidase lysosomal enzyme in the tissues of affected individuals. Objective The objective of this consensus is to review the current guidelines and provide recommendations for a correct diagnosis, evaluation, management, and treatment of patients with PD. Methods We organized a consensus with a foreign guest and national professionals experienced in PD in the areas of clinic, pediatric clinic, laboratory diagnosis, neuropathology, neumonology, nutrition, neurology, metabolic diseases, neuromuscular diseases (NMD) and rehabilitation of patients with MND. We conducted a literature review of the existing publications and articles relevant to EP up to date, individually and in small group meetings organized by field of work and specialty. The final terms of the document were agreed upon by the entire working group. Each participant provided their declaration of conflict of interests. Conclusions The Argentine Consensus for Pompe disease was developed, considering aspects of the pathophysiology, clinical manifestations, diagnosis and treatment of this disease. Being a rare condition for which the available data are limited, these recommendations should be considered as expert opinion.04/2014; DOI:10.1016/j.neuarg.2014.01.006
Journal of the American College of Cardiology 11/2013; 8(4). DOI:10.1016/j.jacc.2013.08.1644 · 15.34 Impact Factor
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ABSTRACT: Autophagic vacuolar myopathies (AVMs) are a group of disorders united by shared histopathological features on muscle biopsy that include the aberrant accumulation of autophagic vacuoles. The classic conditions that compose the AVMs include Pompe Disease, Danon Disease and X-linked myopathy with excessive autophagy (XMEA). Other disorders, including acquired myopathies like chloroquine toxicity, also have features of an autophagic myopathy. This review is focused on XMEA, a myopathy with onset of slowly progressive proximal weakness and elevated serum creatine kinase (2× to 20× normal) typically in the first decade of life. However, both late-adult onset and severe, sometimes lethal, neonatal cases also occur. Skeletal muscle pathology is characterized by numerous cytoplasmic autophagic vacuoles, complex muscle fiber splitting with internalization of capillaries, and complement C5b-9 deposition within vacuoles and along the sarcolemma. The autophagic vacuoles have sarcolemmal features. Mutations in the VMA21 gene at Xq28 cause XMEA by reducing the activity of lysosomal hydrolases. The VMA21 protein regulates the assembly of the V-ATPase required to acidify the lysosome. Increased lysosomal pH and poor degradation of cellular debris may secondarily induce autophagy, the net effect being accumulation of autophagolysosomes. The relationship of XMEA to other lysosomal disorders of muscle and potential therapeutic interventions for XMEA are discussed.Acta Neuropathologica 02/2015; 129(3). DOI:10.1007/s00401-015-1393-4 · 9.78 Impact Factor