All authors received honoraria and support to travel to the consensus paper working group meeting at which the consensus recommendations presented in this manuscript were discussed. Dr Nouriya Al-Sanna’a, Dr Fawziah Al-Sharif, Dr Saeed Bohlega, Dr Mohamed Hamdan, Dr Nawal Makhseed, Dr Yalda Nilipour, Dr Nuri Shembesh, Dr Rawda Sunbul, Dr Seyed Hassan Tonekaboni, Dr Shahriar Nafissi, Dr Laila Selim and Dr Fatimah Alqarni have nothing to declare. Dr Edward Cupler reports receiving honoraria and consulting fees from Genzyme and Novartis and research support from Merck Serono. Dr Waseem Fathalla reports receiving consultancy fees from Genzyme, Shire and Biomarin. Dr Fatma Al Jasmi reports receiving honoraria for lectures, board membership, consultancy fees and grants from Genzyme, Shire, BioMarine, Orphan Europe and Sobi. Dr Mohammed Al Jumah reports receiving consultancy fees from Genzyme, Merck Serono, Novartis, Biogen and Bayer.
All authors contributed extensively to the work presented in this manuscript. EJC was the chairperson of the Pompe Middle East and North Africa Working Group and led the overall development of the manuscript, in addition to providing expert opinion on treatment strategies for management of Pompe disease. NAS reviewed the pathophysiology. SB addressed the epidemiology and genetic basis of Pompe disease and led the consensus discussion on diagnosis of Pompe disease. WF and FA covered the clinical presentation of infantile-onset and late-onset Pompe disease, respectively. MAH reviewed the cardiac issues related to Pompe disease and ERT. MAJ led the consensus discussion on treatment of late-onset Pompe disease and provided updates on the diagnostic approaches along with RS. YN provided expert opinion on muscle pathology in Pompe disease. SHT led the consensus discussion on treatment of infantile onset Pompe disease and also addressed enzyme replacement therapy in infantile and late-onset Pompe disease. FAJ, NM, FAS, SN, NS, and LS presented their experience in management of Pompe disease in their country and outlined the local challenges to optimal management. All authors read and approved the final manuscript.
Pompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms.
An expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities.
These guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring.
These guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.
Muller-Felber W, Horvath R, Gempel K, Podskarbi T, Shin Y, Pongratz D, et al. Late onset Pompe disease: clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patients. Neuromuscul Disord. 2007;17:698–706. PubMed
Chien YH, Lee NC, Huang HJ, Thurberg BL, Tsai FJ, Hwu WL. Later-onset Pompe disease: early detection and early treatment initiation enabled by newborn screening. J Pediatr. 2011;158:1023–7. e1021. PubMed
Mechtler TP, Stary S, Metz TF, De Jesus VR, Greber-Platzer S, Pollak A, et al. Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria. Lancet. 2012;379:335–41. PubMed
Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL, et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68:99–109. PubMed
Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, et al. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve. 2012;45:319–33. PubMed
Llerena Jr JC, Horovitz DM, Marie SK, Porta G, Giugliani R, Rojas MV, et al. The Brazilian consensus on the management of Pompe disease. J Pediatr. 2009;155:S47–56. PubMed
Bembi B, Cerini E, Danesino C, Donati MA, Gasperini S, Morandi L, et al. Management and treatment of glycogenosis type II. Neurology. 2008;71:S12–36. PubMed
Pompe JC. Over idiopathische hypertrophie van het hart. Ned Tijdschr Geneeskd. 1932;76:304–12.
Cori GT. Glycogen structure and enzyme deficiencies in glycogen storage disease. Harvey Lect. 1954;48:145–71.
de Duve C, Pressman BC, Gianetto R, Wattiaux R, Appelmans F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955;60:604–17. PubMedCentral
Baudhuin P, Hers HG, Loeb H. An electron microscopic and biochemical study of type Ii Glycogenosis. Lab Invest. 1964;13:1139–52. PubMed
Brady RO, Pentchev PG, Gal AE, Hibbert SR, Dekaban AS. Replacement therapy for inherited enzyme deficiency. Use of purified glucocerebrosidase in Gaucher’s disease. N Engl J Med. 1974;291:989–93. PubMed
Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med. 1991;324:1464–70. PubMed
Amalfitano A, Bengur AR, Morse RP, Majure JM, Case LE, Veerling DL, et al. Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med. 2001;3:132–8. PubMed
Van den Hout JM, Reuser AJ, de Klerk JB, Arts WF, Smeitink JA, Van der Ploeg AT. Enzyme therapy for pompe disease with recombinant human alpha-glucosidase from rabbit milk. J Inherit Metab Dis. 2001;24:266–74. PubMed
Van den Hout JM, Kamphoven JH, Winkel LP, Arts WF, De Klerk JB, Loonen MC, et al. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics. 2004;113:e448–57. PubMed
Owens J. 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007;6:99–101. PubMed
van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, et al. A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med. 2010;362:1396–406. PubMed
Strothotte S, Strigl-Pill N, Grunert B, Kornblum C, Eger K, Wessig C, et al. Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial. J Neurol. 2010;257:91–7. PubMed
Leslie N, Tinkle BT. Glycogen Storage Disease Type II (Pompe Disease). In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, editors. Gene reviews. Seattle (WA): University of Washington, Seattle; 1993.
Pinto R, Caseiro C, Lemos M, Lopes L, Fontes A, Ribeiro H, et al. Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet. 2004;12:87–92. PubMed
Hirschhorn R, Reuser AJ. Glycogen Storage Disease Type II: Acid Alpha-Glucosidase (Acid Maltase) Deficiency. In: Wonsiewicz MNS, Boyle P, editors. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001. p. 3389–420.
Ausems MG, Verbiest J, Hermans MP, Kroos MA, Beemer FA, Wokke JH, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet. 1999;7:713–6. PubMed
Hamamy H. Consanguineous marriages: preconception consultation in primary health care settings. J Community Genet. 2012;3:185–92. PubMed
Honig J, Martiniuk F, D'Eustachio P, Zamfirescu C, Desnick R, Hirschhorn K, et al. Confirmation of the regional localization of the genes for human acid alpha-glucosidase (GAA) and adenosine deaminase (ADA) by somatic cell hybridization. Ann Hum Genet. 1984;48:49–56. PubMed
Kuo WL, Hirschhorn R, Huie ML, Hirschhorn K. Localization and ordering of acid alpha-glucosidase (GAA) and thymidine kinase (TK1) by fluorescence in situ hybridization. Hum Genet. 1996;97:404–6. PubMed
McCready ME, Carson NL, Chakraborty P, Clarke JT, Callahan JW, Skomorowski MA, et al. Development of a clinical assay for detection of GAA mutations and characterization of the GAA mutation spectrum in a Canadian cohort of individuals with glycogen storage disease, type II. Mol Genet Metab. 2007;92:325–35. PubMed
Wokke JH, Escolar DM, Pestronk A, Jaffe KM, Carter GT, van den Berg LH, et al. Clinical features of late-onset Pompe disease: a prospective cohort study. Muscle Nerve. 2008;38:1236–45. PubMed
Hagemans ML, Winkel LP, Van Doorn PA, Hop WJ, Loonen MC, Reuser AJ, et al. Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain. 2005;128:671–7. PubMed
Schuller A, Wenninger S, Strigl-Pill N, Schoser B. Toward deconstructing the phenotype of late-onset Pompe disease. Am J Med Genet C: Semin Med Genet. 2012;160:80–8.
Spada M, Porta F, Vercelli L, Pagliardini V, Chiado-Piat L, Boffi P, et al. Screening for later-onset Pompe’s disease in patients with paucisymptomatic hyperCKemia. Mol Genet Metab. 2013;109:171–3. PubMed
Dubrovsky A, Corderi J, Lin M, Kishnani PS, Jones HN. Expanding the phenotype of late-onset Pompe disease: tongue weakness: a new clinical observation. Muscle Nerve. 2011;44:897–901. PubMed
Hobson-Webb LD, Jones HN, Kishnani PS. Oropharyngeal dysphagia may occur in late-onset Pompe disease, implicating bulbar muscle involvement. Neuromuscul Disord. 2013;23:319–23. PubMed
Soliman OI, van der Beek NA, van Doorn PA, Vletter WB, Nemes A, Van Dalen BM, et al. Cardiac involvement in adults with Pompe disease. J Intern Med. 2008;264:333–9. PubMed
Laforet P, Petiot P, Nicolino M, Orlikowski D, Caillaud C, Pellegrini N, et al. Dilative arteriopathy and basilar artery dolichoectasia complicating late-onset Pompe disease. Neurology. 2008;70:2063–6. PubMed
Sacconi S, Bocquet JD, Chanalet S, Tanant V, Salviati L, Desnuelle C. Abnormalities of cerebral arteries are frequent in patients with late-onset Pompe disease. J Neurol. 2010;257:1730–3. PubMed
Musumeci O, Catalano N, Barca E, Ravaglia S, Fiumara A, Gangemi G, et al. Auditory system involvement in late onset Pompe disease: a study of 20 Italian patients. Mol Genet Metab. 2012;107:480–4. PubMed
Hanisch F, Rahne T, Plontke SK. Prevalence of hearing loss in patients with late-onset Pompe disease: Audiological and otological consequences. Int J Audiol. 2013;52:816–23. PubMed
van den Berg LE, Zandbergen AA, van Capelle CI, de Vries JM, Hop WC, van den Hout JM, et al. Low bone mass in Pompe disease: muscular strength as a predictor of bone mineral density. Bone. 2010;47:643–9. PubMed
Montagnese F, Barca E, Musumeci O, Mondello S, Migliorato A, Ciranni A, et al. Clinical and molecular aspects of 30 patients with late-onset Pompe disease (LOPD): unusual features and response to treatment. J Neurol. 2015;262:968–78. PubMed
Gutierrez-Rivas E, Bautista J, Vilchez JJ, Muelas N, Diaz-Manera J, Illa I, et al. Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort. Neuromuscul Disord. 2015;25:548–53. PubMed
Preisler N, Lukacs Z, Vinge L, Madsen KL, Husu E, Hansen RS, et al. Late-onset Pompe disease is prevalent in unclassified limb-girdle muscular dystrophies. Mol Genet Metab. 2013;110:287–9. PubMed
Ausems MG, Lochman P, van Diggelen OP, Ploos van Amstel HK, Reuser AJ, Wokke JH. A diagnostic protocol for adult-onset glycogen storage disease type II. Neurology. 1999;52:851–3. PubMed
American Thoracic Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002;166:518–624.
Prigent H, Orlikowski D, Laforet P, Letilly N, Falaize L, Pellegrini N, et al. Supine volume drop and diaphragmatic function in adults with Pompe disease. Eur Respir J. 2012;39:1545–6. PubMed
Shah DU, Darras BT, Markowitz JA, Jones Jr HR, Kang PB. The spectrum of myotonic and myopathic disorders in a pediatric electromyography laboratory over 12 years. Pediatr Neurol. 2012;47:97–100. PubMed
Winchester B, Bali D, Bodamer OA, Caillaud C, Christensen E, Cooper A, et al. Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report from an international consensus meeting. Mol Genet Metab. 2008;93:275–81. PubMed
Umapathysivam K, Hopwood JJ, Meikle PJ. Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease. Clin Chem. 2001;47:1378–83. PubMed
Kroos M, Hoogeveen-Westerveld M, Michelakakis H, Pomponio R, Van der Ploeg A, Halley D, et al. Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants. Hum Mutat. 2012;33:1161–5. PubMed
Baethmann M, Straub V, Reuser A. Pompe disease. Uni-Med Science: Bremen; 2008.
Winkel LP, Hagemans ML, van Doorn PA, Loonen MC, Hop WJ, Reuser AJ, et al. The natural course of non-classic Pompe’s disease; a review of 225 published cases. J Neurol. 2005;252:875–84. PubMed
Carlier RY, Laforet P, Wary C, Mompoint D, Laloui K, Pellegrini N, et al. Whole-body muscle MRI in 20 patients suffering from late onset Pompe disease: Involvement patterns. Neuromuscul Disord. 2011;21:791–9. PubMed
Gaeta M, Barca E, Ruggeri P, Minutoli F, Rodolico C, Mazziotti S, et al. Late-onset Pompe disease (LOPD): Correlations between respiratory muscles CT and MRI features and pulmonary function. Mol Genet Metab. 2013;110:290–6. PubMed
Toscano A, Schoser B. Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review. J Neurol. 2013;260:951–9. PubMed
Nicolino M, Byrne B, Wraith JE, Leslie N, Mandel H, Freyer DR, et al. Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med. 2009;11:210–9. PubMed
Deegan PB, Cox TM, Waldek S, Lachmann R, Ramaswami U, Jessop E: Guidelines for the Investigation and Management of Late Onset Acid Maltase Deficiency (Type II Glycogen Storage Disease / Pompe Disease). [ http://www.specialisedservices.nhs.uk/library/23/Guidelines_for_Late_Onset_Pompe_Disease.pdf]
Corporation G. Lumizyme prescibing information. Cambridge: MA, USA; 2010.
Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45. London, UK: Her Majesty’s Stationary Office; 1976.
Beenakker EA, van der Hoeven JH, Fock JM, Maurits NM. Reference values of maximum isometric muscle force obtained in 270 children aged 4–16 years by hand-held dynamometry. Neuromuscul Disord. 2001;11:441–6. PubMed
American Thoracic Society. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166:111–7.
Hagemans ML, Janssens AC, Winkel LP, Sieradzan KA, Reuser AJ, Van Doorn PA, et al. Late-onset Pompe disease primarily affects quality of life in physical health domains. Neurology. 2004;63:1688–92. PubMed
Gungor D, Schober AK, Kruijshaar ME, Plug I, Karabul N, Deschauer M, et al. Pain in adult patients with Pompe disease: a cross-sectional survey. Mol Genet Metab. 2013;109:371–6. PubMed
Patel TT, Banugaria SG, Case LE, Wenninger S, Schoser B, Kishnani PS. The impact of antibodies in late-onset Pompe disease: a case series and literature review. Mol Genet Metab. 2012;106:301–9. PubMed
Montazeri A, Goshtasebi A, Vahdaninia M, Gandek B. The Short Form Health Survey (SF-36): translation and validation study of the Iranian version. Qual Life Res. 2005;14:875–82. PubMed
Mehraban D, Naderi G, Salehi M. Development of SF-36 questionnaire in the measurement of quality of life in patients on renal replacement therapy in Iran. Saudi J Kidney Dis Transpl. 2003;14:15–7. PubMed
Arad M, Maron BJ, Gorham JM, Johnson Jr WH, Saul JP, Perez-Atayde AR, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med. 2005;352:362–72. PubMed
Bernstein DL, Bialer MG, Mehta L, Desnick RJ. Pompe disease: dramatic improvement in gastrointestinal function following enzyme replacement therapy. A report of three later-onset patients. Mol Genet Metab. 2010;101:130–3. PubMed
Jones HN, Crisp KD, Asrani P, Sloane R, Kishnani PS. Quantitative assessment of lingual strength in late-onset Pompe disease. Muscle Nerve. 2015;51:731–5. PubMed
Ravaglia S, Danesino C, Moglia A, Costa A, Cena H, Maccarini L, et al. Changes in nutritional status and body composition during enzyme replacement therapy in adult-onset type II glycogenosis. Eur J Neurol. 2010;17:957–62. PubMed
Mobarhan S, Pintozzi RL, Damle P, Friedman H. Treatment of acid maltase deficiency with a diet high in branched-chain amino acids. JPEN J Parenter Enteral Nutr. 1990;14:210–2. PubMed
Bodamer OA, Halliday D, Leonard JV. The effects of l-alanine supplementation in late-onset glycogen storage disease type II. Neurology. 2000;55:710–2. PubMed
Hagemans ML, Winkel LP, Hop WC, Reuser AJ, Van Doorn PA, Van der Ploeg AT. Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology. 2005;64:2139–41. PubMed
Slonim AE, Bulone L, Goldberg T, Minikes J, Slonim E, Galanko J, et al. Modification of the natural history of adult-onset acid maltase deficiency by nutrition and exercise therapy. Muscle Nerve. 2007;35:70–7. PubMed
Terzis G, Dimopoulos F, Papadimas GK, Papadopoulos C, Spengos K, Fatouros I, et al. Effect of aerobic and resistance exercise training on late-onset Pompe disease patients receiving enzyme replacement therapy. Mol Genet Metab. 2011;104:279–83. PubMed
Terzis G, Krase A, Papadimas G, Papadopoulos C, Kavouras SA, Manta P. Effects of exercise training during infusion on late-onset Pompe disease patients receiving enzyme replacement therapy. Mol Genet Metab. 2012;107:669–73. PubMed
Papadimas GK, Terzis G, Methenitis S, Spengos K, Papadopoulos C, Vassilopoulou S, et al. Body composition analysis in late-onset Pompe disease. Mol Genet Metab. 2011;102:41–3. PubMed
Refai D, Lev R, Cross DT, Shimony JS, Leonard JR. Thrombotic complications of a basilar artery aneurysm in a young adult with Pompe disease. Surg Neurol. 2008;70:518–20. PubMed
El-Gharbawy AH, Bhat G, Murillo JE, Thurberg BL, Kampmann C, Mengel KE, et al. Expanding the clinical spectrum of late-onset Pompe disease: dilated arteriopathy involving the thoracic aorta, a novel vascular phenotype uncovered. Mol Genet Metab. 2011;103:362–6. PubMed
Cilliers HJ, Yeo ST, Salmon NP. Anaesthetic management of an obstetric patient with Pompe disease. Int J Obstet Anesth. 2008;17:170–3. PubMed
EMA. Myozyme: EPAR - Product Information. [ http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000636/WC500032125.pdf]
de Vries JM, Brugma JD, Ozkan L, Steegers EA, Reuser AJ, van Doorn PA, et al. First experience with enzyme replacement therapy during pregnancy and lactation in Pompe disease. Mol Genet Metab. 2011;104:552–5. PubMed
ClinicalTrials.gov. Safety and Efficacy Evaluation of Repeat neoGAA Dosing in Late Onset Pompe Disease Patients. [ http://clinicaltrials.gov/show/NCT01898364]
Maga JA, Zhou J, Kambampati R, Peng S, Wang X, Bohnsack RN, et al. Glycosylation-independent lysosomal targeting of acid alpha-glucosidase enhances muscle glycogen clearance in pompe mice. J Biol Chem. 2013;288:1428–38. PubMed
BioMarin. Pompe Clinical Trials. [ https://www.bmrn.com/pipeline/clinical-trials/pompe.php]
Lun Y, Feng J, Xu S, Soska R, Frascella M, Garcia A, et al. Exploring the Use of a Co-formulated Pharmacological Chaperone AT2220 with Recombinant Acid Alpha-Glucosidase for Pompe Disease. In: Proceedings of the LDN World 2013; Orlando, USA. 2013.
Kishnani P, Tarnopolsky M, Byrne B, Sivakumar K, Roberts M, Finanger E, et al. Phase 2a Study to Investigate Drug-Drug Interactions between Escalating Doses of AT2220 (Duvoglustat Hydrochloride) and Acid Alfa-Glucosidase in Subjects with Pompe Disease. In: Proceedings of the LDN WORLD 2013; Orlando, USA. 2013.
Amicus Therapeutics: Amicus Therapeutics Begins Phase 2 Clinical Trial of AT2220 in Pompe Disease. [ http://ir.amicustherapeutics.com/releasedetail.cfm?ReleaseID=313541]
Amicus Therapeutics: Amicus Therapeutics Suspends Enrollment for Phase 2 Clinical Trial of AT2220 for Pompe Disease. [ http://ir.amicustherapeutics.com/releasedetail.cfm?ReleaseID=368188]
Smith BK, Collins SW, Conlon TJ, Mah CS, Lawson LA, Martin AD, et al. Phase I/II trial of adeno-associated virus-mediated alpha-glucosidase gene therapy to the diaphragm for chronic respiratory failure in Pompe disease: initial safety and ventilatory outcomes. Hum Gene Ther. 2013;24:630–40. PubMedPubMedCentral
AANEM. Diagnostic criteria for late-onset (childhood and adult) Pompe disease. Muscle Nerve. 2009;40:149–60.
- Diagnosis and treatment of late-onset Pompe disease in the Middle East and North Africa region: consensus recommendations from an expert group
Fatma Al Jasmi
Mohammed Al Jumah
Edward J. Cupler
Mohamed A. Hamdan
Seyed Hassan Tonekaboni
The MENA Pompe Working Group
- BioMed Central