We searched Pubmed for articles with the terms “Pompe disease”, “acid alpha-glucosidase deficiency”, “acid maltase deficiency”, “glycogenosis type II”, and “enzyme (replacement) therapy”. We mainly selected publications in English from the past 7 years, but did not exclude commonly referenced and highly regarded older publications. For treatment, we focused on enzyme therapy. Articles on gene therapy were excluded, because they were beyond the scope of this review. For detailed
SeriesPompe's disease
Introduction
Pompe's disease (Online Mendelian Inheritance in Man [OMIM] number 232300) is an inherited metabolic myopathy. It is a generalised glycogenosis characterised by lysosomal glycogen storage caused by deficiency of the lysosomal enzyme acid α-glucosidase. Pompe's disease has an estimated frequency of one in 40 000 in African-American, one in 50 000 in Chinese, one in 40 000 in Dutch, and one in 146 000 in Australian populations.1, 2, 3, 4, 5, 6
Synonyms for the disease are glycogen-storage disease type II and acid-maltase deficiency. This disease has been untreatable, but approval in 2006 of enzyme replacement therapy with recombinant human acid α-glucosidase has shown the potential to substantially alter its prognosis. This review addresses the latest insights into Pompe's disease, with a focus on diagnostic and therapeutic challenges.
Section snippets
Clinical features
Pompe's disease presents as a spectrum of features in which symptoms can manifest at any age (figure 1).7 At the severe end of the spectrum is a subgroup of patients with a clearly defined course. This classic infantile form was first described by Pompe in 1932 and usually presents in patients within the first months of life. The median age of onset ranges from 1·6 to 2·0 months.8, 9, 10 Presenting symptoms are feeding difficulties, failure to thrive, respiratory infections, hypotonia, and very
Enzymatic and molecular diagnosis
All patients have a deficiency of the lysosomal enzyme acid α-glucosidase, and can be diagnosed on the basis of this feature.34 However, the sensitivity and specificity of the enzymatic procedure depends on the choice of tissue specimen, type of substrate, and assay conditions. Of the various tissue specimens that are used for diagnosis, cultured skin fibroblasts have by far the highest acid α-glucosidase activity and do not contain neutral α-glucosidase activities that interfere with the assay
GAA genotype and clinical course
Pompe's disease is inherited in an autosomal recessive manner. No cases of affected carriers have been documented. Thus, both GAA alleles need to harbour a pathogenic mutation before the phenotype develops. Many of the reported mutations were characterised. We usually know precisely how they affect the splicing process, the GAA-mRNA stability, or the biosynthesis of acid α-glucosidase (including the various post-translational modification steps, the intracellular transport, and finally the
Pathophysiology
Accumulation of lysosomal glycogen starts when the acid α-glucosidase activity decreases below critical.2 This threshold amount seems to vary depending on the organ. In knockout mouse models of Pompe's disease with complete enzyme deficiency, storage was seen in almost every tissue and cell type—ie, liver, heart, and skeletal muscle, smooth-muscle cells of the gastrointestinal tract, bladder, blood-vessel walls, kidney, spleen, endothelial cells, and Schwann cells and in the perineurium of
Enzyme replacement therapy
In the 1960s, Pompe's disease was the first lysosomal storage disorder for which attempts at enzyme replacement therapy were undertaken in individual patients with enzyme preparations from Aspergillus niger and human placenta. However, these attempts were without clinical benefit. With experience, we clearly know that inappropriate enzyme source and insufficient dosing were the causes of failure.92, 93 An important step forward was the knowledge that cell-surface receptors helped with uptake of
Conclusion
Several important lessons have been learned from the studies in mice and man, which showed that the acid α-glucosidase activity in blood needs to surpass a specific threshold to elicit a therapeutic response in skeletal muscles. Studies of mice and quail showed that this threshold was achieved at a dose of about 20 mg/kg.101, 103, 104, 105, 109, 110, 126 Further, studies showed that young mice with mild pathological changes in the tissue responded better to therapy than old mice with advanced
Search strategy and selection criteria
References (137)
- et al.
Identification of two subtypes of infantile acid maltase deficiency
J Pediatr
(2000) - et al.
Diagnostic challenges for Pompe disease: an under-recognized cause of floppy baby syndrome
Genet Med
(2006) - et al.
Development of obstruction to ventricular outflow and impairment of inflow in glycogen storage disease of the heart: serial echocardiographic studies from birth to death at 6 months
Am Heart J
(1992) - et al.
Electrocardiographic response to enzyme replacement therapy for Pompe disease
Genet Med
(2006) - et al.
Hearing loss in infantile Pompe's disease and determination of underlying pathology in the knockout mouse
Neurobiol Dis
(2004) - et al.
Pompe disease diagnosis and management guideline
Genet Med
(2006) - et al.
Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease
J Pediatr
(2006) - et al.
Juvenile onset acid maltase deficiency presenting as a rigid spine syndrome
Neuromuscul Disord
(2006) - et al.
Correlation of acid alpha-glucosidase and glycogen content in skin fibroblasts with age of onset in Pompe disease
Clin Chim Acta
(2005) - et al.
A new diagnostic assay for glycogen storage disease type II in mixed leukocytes
Mol Genet Metab
(2006)
The use of acarbose inhibition in the measurement of acid alpha-glucosidase activity in blood lymphocytes for the diagnosis of Pompe disease
Genet Med
Glycogen storage disease type II: enzymatic screening in dried blood spots on filter paper
Clin Chim Acta
Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease
Genet Med
Newborn screening for lysosomal storage disorders
Mol Genet Metab
Rapid diagnosis of late-onset Pompe disease by fluorometric assay of alpha-glucosidase activities in dried blood spots
Mol Genet Metab
High incidence of later-onset fabry disease revealed by newborn screening
Am J Hum Genet
Deletion of exon 18 is a frequent mutation in glycogen storage disease type II
Biochem Biophys Res Comm
The African origin of the common mutation in African American patients with glycogen-storage disease type II [letter]
Am J Hum Genet
Biosynthesis of lysosomal enzymes in fibroblasts. Synthesis as precursors of higher molecular weight
J Biol Chem
Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues
J Biol Chem
Physiological Correction of Pompe Disease by Systemic Delivery of Adeno-associated Virus Serotype 1 Vectors
Mol Ther
Enhanced efficacy of an AAV vector encoding chimeric, highly secreted acid alpha-glucosidase in glycogen storage disease type II
Mol Ther
Chemical chaperones improve transport and enhance stability of mutant alpha- glucosidases in glycogen storage disease type II
Mol Genet Metab
Pharmacological Enhancement of Mutated alpha-Glucosidase Activity in Fibroblasts from Patients with Pompe Disease
Mol Ther
Targeted disruption of the acid alpha-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II
J Biol Chem
Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease
Mol Ther
Characterization of pre- and post-treatment pathology after enzyme replacement therapy for Pompe disease
Lab Invest
Effects of non-contractile inclusions on mechanical performance of skeletal muscle
J Biomech
Uptake and stability of human and bovine acid alpha-glucosidase in cultured fibroblasts and skeletal muscle cells from glycogenosis type II patients
Exp Cell Res
Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling
Europ J Hum Genet
Glycogen Storage Disease Type II (GSDII)
Pompe's disease in Chinese and prenatal diagnosis by determination of alpha-glucosidase activity
J Inherit Metabol Dis
Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease
Am J Med Genet
The frequency of lysosomal storage diseases in The Netherlands
Hum Genet
Prevalence of lysosomal storage disorders
JAMA
The spectrum and diagnosis of acid maltase deficiency
Neurology
The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature
Pediatrics
A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease
J Pediatr
Electrophysiological mechanism of the short PR interval in Pompe disease
Am J Dis Child
Fractures in children with Pompe disease: a potential long-term complication
Pediatr Radiol
Juvenile and adult-onset acid maltase deficiency in France: genotype-phenotype correlation
Neurology
Genotype-phenotype correlation in adult-onset acid maltase deficiency
Ann Neurol
The natural course of non-classic Pompe's disease; a review of 225 published cases
J Neurol
Disease severity in children and adults with Pompe disease related to age and disease duration
Neurology
A rare presentation of childhood pompe disease: cardiac involvement provoked by Epstein-Barr virus infection
Pediatrics
Efficacy of multidisciplinary approach in the treatment of two cases of nonclassical infantile glycogenosis type II
J Inherit Metab Dis
Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients
Brain
Respiratory failure in Pompe disease: treatment with noninvasive ventilation
Neurology
Sleep-disordered breathing and respiratory failure in acid maltase deficiency
Neurology
Respiratory insufficiency and limb muscle weakness in adults with Pompe's disease
Eur Respir J
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