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01-12-2020 | Muscular Dystrophy | Research

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

Authors: Jorge A. Bevilacqua, Maria del Rosario Guecaimburu Ehuletche, Abayuba Perna, Alberto Dubrovsky, Marcondes C. Franca Jr, Steven Vargas, Madhuri Hegde, Kristl G. Claeys, Volker Straub, Nadia Daba, Roberta Faria, Magali Periquet, Susan Sparks, Nathan Thibault, Roberto Araujo

Published in: Orphanet Journal of Rare Diseases | Issue 1/2020

Abstract

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. Patients with PMW, with or without respiratory symptoms, were included in this study of Latin American patients to evaluate the profile of variants for the included genes related to LGMD recessive (R) and LOPD and the frequency of variants in each gene among this patient population.

Results

Over 20 institutions across Latin America (Brazil, Argentina, Peru, Ecuador, Mexico, and Chile) enrolled 2103 individuals during 2016 and 2017. Nine autosomal recessive LGMDs and Pompe disease were investigated in a 10-gene panel (ANO5, CAPN3, DYSF, FKRP, GAA, SGCA, SGCB, SGCD, SGCG, TCAP) based on reported disease frequency in Latin America. Sequencing was performed with Illumina’s NextSeq500 and variants were classified according to ACMG guidelines; pathogenic and likely pathogenic were treated as one category (P) and variants of unknown significance (VUS) are described. Genetic variants were identified in 55.8% of patients, with 16% receiving a definitive molecular diagnosis; 39.8% had VUS. Nine patients were identified with Pompe disease.

Conclusions

The results demonstrate the effectiveness of this targeted genetic panel and the importance of including Pompe disease in the differential diagnosis for patients presenting with PMW.

Zatz M, de Paula F, Starling A, Vainzof M. The 10 autosomal recessive limb-girdle muscular dystrophies. Neuromuscul Disord. 2013;13(7–8):532–44.

Mitsuhashi S, Kang PB. Update on the genetics of limb girdle muscular dystrophy. Semin Pediatr Neurol. 2012;19(4):211–8. https://doi.org/10.1016/j.spen.2012.09.008.CrossRefPubMed

Reddy HM, Cho KA, Lek M, Estrella E, Valkanas E, Jones MD, et al. The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States. J Hum Genet. 2017;62(2):243–52. https://doi.org/10.1038/jhg.2016.116.CrossRefPubMed

Straub V, Murphy A, Udd B. 229th ENMC international workshop: limb girdle muscular dystrophies - nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017. Neuromuscul Disord. 2018;28(8):702–10. https://doi.org/10.1016/j.nmd.2018.05.007.CrossRef

Mahmood OA, Jiang XM. Limb-girdle muscular dystrophies: where next after six decades from the first proposal (review). Mol Med Rep. 2014;9(5):1515–32. https://doi.org/10.3892/mmr.2014.2048.CrossRefPubMedPubMedCentral

Nallamilli BRR, Chakravorty S, Kesari A, Tanner A, Ankala A, Schneider T, et al. Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients. Ann Clin Translational Neurol. 2018;5(12):1574–87. https://doi.org/10.1002/acn3.649.CrossRef

Bushby KM. The limb-girdle muscular dystrophies-multiple genes, multiple mechanisms. Hum Mol Genet. 1999;8(10):1875–82.CrossRef

Nigro V, Savarese M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol. 2014;33(1):1–12.PubMedPubMedCentral

Lorenzoni PJ, Kay CSK, Higashi NS, D'Almeida V, Werneck LC, Scola RH. Late-onset Pompe disease: what is the prevalence of limb-girdle muscular weakness presentation? Arq Neuropsiquiatr. 2018;76(4):247–51. https://doi.org/10.1590/0004-282x20180018.CrossRefPubMed

10.

Bodamer OA, Scott CR, Giugliani R. Newborn screening for Pompe disease. Pediatrics. 2017;140(Suppl 1):S4–S13. https://doi.org/10.1542/peds.2016-0280C.CrossRefPubMed

11.

Leslie N, Bailey L. Pompe Disease. 2007 Aug 31 [Updated 2017 May 11]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1261.

12.

Kronn DF, Day-Salvatore D, Hwu WL, Jones SA, Nakamura K, Okuyama T, et al. Management of confirmed newborn-screened patients with Pompe disease across the disease spectrum. Pediatrics. 2017;140(Suppl 1):S24–45. https://doi.org/10.1542/peds.2016-0280E.CrossRef

13.

Gungor D, Reuser AJ. How to describe the clinical spectrum in Pompe disease? Am J Med Genet Part A. 2013;161a(2):399–400. https://doi.org/10.1002/ajmg.a.35662.CrossRefPubMed

14.

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(Pt 3):671–7. https://doi.org/10.1093/brain/awh384.CrossRefPubMed

15.

Reuser AJ, Hirschhorn R, Kroos MA. Pompe Disease: Glycogen Storage Disease Type II, Acid α-Glucosidase (Acid Maltase) Deficiency. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62641992.

16.

van der Ploeg AT, Reuser AJ. Pompe's disease. Lancet. 2008;372(9646):1342–53. https://doi.org/10.1016/s0140-6736(08)61555-x.CrossRefPubMed

17.

Gutiérrez-Rivas E, Bautista J, Vílchez JJ, Muelas N, Díaz-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(7):548–53. https://doi.org/10.1016/j.nmd.2015.04.008.CrossRefPubMed

18.

Liao HC, Chiang CC, Niu DM, Wang CH, Kao SM, Tsai FJ, et al. Detecting multiple lysosomal storage diseases by tandem mass spectrometry—a national newborn screening program in Taiwan. Clin Chim Acta. 2014;431:80–6. https://doi.org/10.1016/j.cca.2014.01.030.CrossRef

19.

Hopkins PV, Campbell C, Klug T, Rogers S, Raburn-Miller J, Kiesling J. Lysosomal storage disorder screening implementation: findings from the first six months of full population pilot testing in Missouri. J Pediatr. 2015;166(1):172–7. https://doi.org/10.1016/j.jpeds.2014.09.023.CrossRefPubMed

20.

Klinge L, Straub V, Neudorf U, Schaper J, Bosbach T, Gorlinger K, et al. Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial. Neuromuscul Disord. 2005;15(1):24–31. https://doi.org/10.1016/j.nmd.2004.10.009.CrossRefPubMed

21.

Klinge L, Straub V, Neudorf U, Voit T. Enzyme replacement therapy in classical infantile pompe disease: results of a ten-month follow-up study. Neuropediatrics. 2005;36(1):6–11. https://doi.org/10.1055/s-2005-837543.CrossRefPubMed

22.

Kishnani PS, Nicolino M, Voit T, Rogers RC, Tsai AC, Waterson J, et al. Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. J Pediatr. 2006;149(1):89–97. https://doi.org/10.1016/j.jpeds.2006.02.035.CrossRefPubMedPubMedCentral

23.

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(2):99–109. https://doi.org/10.1212/01.wnl.0000251268.41188.04.CrossRefPubMed

24.

Kishnani PS, Corzo D, Leslie ND, Gruskin D, Van der Ploeg A, Clancy JP, et al. Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res. 2009;66(3):329–35. https://doi.org/10.1203/PDR.0b013e3181b24e94.CrossRefPubMedPubMedCentral

25.

Van den Hout H, Reuser AJ, Vulto AG, Loonen MC, Cromme-Dijkhuis A, Van der Ploeg AT. Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet. 2000;356(9227):397–8.CrossRef

26.

Schoser B, Stewart A, Kanters S, Hamed A, Jansen J, Chan K, et al. Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis. J Neurol. 2017;264:621–30. https://doi.org/10.1007/s00415-016-8219-8.CrossRefPubMed

27.

van Capelle CI, van der Beek NA, Hagemans ML, Arts WF, Hop WC, Lee P, et al. Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study. Neuromuscul Disord. 2010;20(12):775–82. https://doi.org/10.1016/j.nmd.2010.07.277.CrossRefPubMed

28.

van Capelle CI, Winkel LP, Hagemans ML, Shapira SK, Arts WF, van Doorn PA, et al. Eight years experience with enzyme replacement therapy in two children and one adult with Pompe disease. Neuromuscul Disord. 2008;18(6):447–52. https://doi.org/10.1016/j.nmd.2008.04.009.CrossRefPubMed

29.

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(1):91–7. https://doi.org/10.1007/s00415-009-5275-3.CrossRefPubMed

30.

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(15):1396–406. https://doi.org/10.1056/NEJMoa0909859.CrossRefPubMed

31.

Tsai AC, Hung YW, Harding C, Koeller DM, Wang J, Wong LC. Next generation deep sequencing corrects diagnostic pitfalls of traditional molecular approach in a patient with prenatal onset of Pompe disease. Am J Med Genet Part A. 2017;173(9):2500–4. https://doi.org/10.1002/ajmg.a.38333.CrossRefPubMed

32.

Savarese M, Di Fruscio G, Mutarelli M, Torella A, Magri F, Santorelli FM, et al. MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples. Acta Neuropathol Commun. 2014;2:100. https://doi.org/10.1186/s40478-014-0100-3.CrossRefPubMedPubMedCentral

33.

Kuhn M, Glaser D, Joshi PR, Zierz S, Wenninger S, Schoser B, et al. Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy. J Neurol. 2016;263(4):743–50. https://doi.org/10.1007/s00415-016-8036-0.CrossRefPubMed

34.

Lukacs Z, Nieves Cobos P, Wenninger S, Willis TA, Guglieri M, Roberts M, et al. Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness. Neurology. 2016;87(3):295–8. https://doi.org/10.1212/wnl.0000000000002758.CrossRefPubMedPubMedCentral

35.

Palmio J, Auranen M, Kiuru-Enari S, Lofberg M, Bodamer O, Udd B. Screening for late-onset Pompe disease in Finland. Neuromuscul Disord. 2014;24(11):982–5. https://doi.org/10.1016/j.nmd.2014.06.438.CrossRefPubMed

36.

Savarese M, Torella A, Musumeci O, Angelini C, Astrea G, Bello L, et al. Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease. Neuromuscul Disord. 2018;28(7):586–91. https://doi.org/10.1016/j.nmd.2018.03.011.CrossRefPubMed

37.

Saudi Mendeliome Group. Comprehensive gene panels provide advantages over clinical exome sequencing for Mendelian diseases. Genome Biol. 2015;16:134. https://doi.org/10.1186/s13059-015-0693-2.CrossRefPubMedCentral

38.

Narayanaswami P, Carter G, David W, Weiss M, Amato AA. Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology. 2015;84(16):1720–1.

39.

Pegoraro E, Hoffman EP. Limb-Girdle Muscular Dystrophy Overview. 2000 Jun 8 [Updated 2012 Aug 30]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1408/.

40.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24. https://doi.org/10.1038/gim.2015.30.CrossRefPubMedPubMedCentral

41.

den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, Roux AF, Smith T, Antonarakis SE, Taschner PE. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat. 2016;37(6):564–9. https://doi.org/10.1002/humu.22981.CrossRef

42.

Ankala A, da Silva C, Gualandi F, Ferlini A, Bean LJ, Collins C, et al. A comprehensive genomic approach for neuromuscular diseases gives a high diagnostic yield. Ann Neurol. 2015;77(2):206–14. https://doi.org/10.1002/ana.24303.CrossRefPubMed

43.

Chin EL, da Silva C, Hegde M. Assessment of clinical analytical sensitivity and specificity of next-generation sequencing for detection of simple and complex mutations. BMC Genet. 2013;14:6. https://doi.org/10.1186/1471-2156-14-6.CrossRefPubMedPubMedCentral

44.

Dai Y, Wei X, Zhao Y, Ren H, Lan Z, Yang Y, et al. A comprehensive genetic diagnosis of Chinese muscular dystrophy and congenital myopathy patients by targeted next-generation sequencing. Neuromuscul Disord. 2015;25(8):617–24. https://doi.org/10.1016/j.nmd.2015.03.002.CrossRefPubMed

45.

Evila A, Arumilli M, Udd B, Hackman P. Targeted next-generation sequencing assay for detection of mutations in primary myopathies. Neuromuscul Disord. 2016;26(1):7–15. https://doi.org/10.1016/j.nmd.2015.10.003.CrossRefPubMed

46.

Gargis AS, Kalman L, Berry MW, Bick DP, Dimmock DP, Hambuch T, et al. Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol. 2012;30(11). https://doi.org/10.1038/nbt.2403.CrossRef

47.

Ghaoui R, Cooper ST, Lek M, Jones K, Corbett A, Reddel SW, et al. Use of whole-exome sequencing for diagnosis of limb-girdle muscular dystrophy: outcomes and lessons learned. JAMA Neurol. 2015;72(12):1424–32. https://doi.org/10.1001/jamaneurol.2015.2274.CrossRefPubMed

48.

Jones MA, Bhide S, Chin E, Ng BG, Rhodenizer D, Zhang VW, et al. Targeted PCR-based enrichment and next generation sequencing for diagnostic testing of congenital disorders of glycosylation (CDG). Genet Med. 2011;13(11):921–32. https://doi.org/10.1097/GIM.0b013e318226fbf2.CrossRefPubMedPubMedCentral

49.

Jones MA, Rhodenizer D, da Silva C, Huff IJ, Keong L, Bean LJ, et al. Molecular diagnostic testing for congenital disorders of glycosylation (CDG): detection rate for single gene testing and next generation sequencing panel testing. Mol Genet Metab. 2013;110(1–2):78–85. https://doi.org/10.1016/j.ymgme.2013.05.012.CrossRefPubMed

50.

Laing NG. Genetics of neuromuscular disorders. Crit Rev Clin Lab Sci. 2012;49(2):33–48. https://doi.org/10.3109/10408363.2012.658906.CrossRefPubMed

51.

Monies D, Alhindi HN, Almuhaizea MA, Abouelhoda M, Alazami AM, Goljan E, et al. A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies. Hum Genomics. 2016;10(1):32. https://doi.org/10.1186/s40246-016-0089-8.CrossRefPubMedPubMedCentral

52.

Narayanaswami P. Dismantling limb-girdle muscular dystrophy: the role of whole-exome sequencing. JAMA Neurol. 2015;72(12):1409–11. https://doi.org/10.1001/jamaneurol.2015.2749.CrossRefPubMed

53.

Nishikawa A, Mitsuhashi S, Miyata N, Nishino I. Targeted massively parallel sequencing and histological assessment of skeletal muscles for the molecular diagnosis of inherited muscle disorders. J Med Genet. 2017;54(2):104–10. https://doi.org/10.1136/jmedgenet-2016-104073.CrossRefPubMed

54.

Rehm HL. Disease-targeted sequencing: a cornerstone in the clinic. Nat Rev Genet. 2013;14(4):295–300. https://doi.org/10.1038/nrg3463.CrossRefPubMedPubMedCentral

55.

Rocha CT, Hoffman EP. Limb-girdle and congenital muscular dystrophies: current diagnostics, management, and emerging technologies. Curr Neurol Neurosci Rep. 2010;10(4):267–76. https://doi.org/10.1007/s11910-010-0119-1.CrossRefPubMedPubMedCentral

56.

Savarese M, Di Fruscio G, Torella A, Fiorillo C, Magri F, Fanin M, et al. The genetic basis of undiagnosed muscular dystrophies and myopathies: results from 504 patients. Neurology. 2016;87(1):71–6. https://doi.org/10.1212/wnl.0000000000002800.CrossRefPubMedPubMedCentral

57.

Seong MW, Cho A, Park HW, Seo SH, Lim BC, Seol D, et al. Clinical applications of next-generation sequencing-based gene panel in patients with muscular dystrophy: Korean experience. Clin Genet. 2016;89(4):484–8. https://doi.org/10.1111/cge.12621.CrossRefPubMed

58.

Stehlikova K, Skalova D, Zidkova J, Haberlova J, Vohanka S, Mazanec R, et al. Muscular dystrophies and myopathies: the spectrum of mutated genes in the Czech Republic. Clin Genet. 2017;91(3):463–9. https://doi.org/10.1111/cge.12839.CrossRefPubMed

59.

Valencia CA, Ankala A, Rhodenizer D, Bhide S, Littlejohn MR, Keong LM, et al. Comprehensive mutation analysis for congenital muscular dystrophy: a clinical PCR-based enrichment and next-generation sequencing panel. PLoS One. 2013;8(1):e53083. https://doi.org/10.1371/journal.pone.0053083.CrossRefPubMedPubMedCentral

60.

Valencia CA, Rhodenizer D, Bhide S, Chin E, Littlejohn MR, Keong LM, et al. Assessment of target enrichment platforms using massively parallel sequencing for the mutation detection for congenital muscular dystrophy. J Mol Diagn. 2012;14(3):233–46. https://doi.org/10.1016/j.jmoldx.2012.01.009.CrossRefPubMedPubMedCentral

61.

Xue Y, Ankala A, Wilcox WR, Hegde MR. Solving the molecular diagnostic testing conundrum for Mendelian disorders in the era of next-generation sequencing: single-gene, gene panel, or exome/genome sequencing. Genet Med. 2015;17(6):444–51. https://doi.org/10.1038/gim.2014.122.CrossRefPubMed

62.

Yu M, Zheng Y, Jin S, Gang Q, Wang Q, Yu P, et al. Mutational spectrum of Chinese LGMD patients by targeted next-generation sequencing. PLoS One. 2017;12(4):e0175343. https://doi.org/10.1371/journal.pone.0175343.CrossRefPubMedPubMedCentral

63.

Levesque S, Auray-Blais C, Gravel E, Boutin M, Dempsey-Nunez L, Jacques PE, et al. Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing. Orphanet J Rare Dis. 2016;11:8. https://doi.org/10.1186/s13023-016-0390-6.CrossRefPubMedPubMedCentral

64.

Angelini C, Savarese M, Fanin M, Nigro V. Next generation sequencing detection of late onset Pompe disease. Muscle Nerve. 2016;53(6):981–3. https://doi.org/10.1002/mus.25042.CrossRefPubMed

65.

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(3):287–9. https://doi.org/10.1016/j.ymgme.2013.08.005.CrossRefPubMed

66.

Johnson K, Bertoli M, Phillips L, Topf A, Van den Bergh P, Vissing J, et al. Detection of variants in dystroglycanopathy-associated genes through the application of targeted whole-exome sequencing analysis to a large cohort of patients with unexplained limb-girdle muscle weakness. Skelet Muscle. 2018;8(1):23. https://doi.org/10.1186/s13395-018-0170-1.CrossRefPubMedPubMedCentral

67.

Johnson K, Topf A, Bertoli M, Phillips L, Claeys KG, Stojanovic VR, et al. Identification of GAA variants through whole exome sequencing targeted to a cohort of 606 patients with unexplained limb-girdle muscle weakness. Orphanet J Rare Dis. 2017;12(1):173. https://doi.org/10.1186/s13023-017-0722-1.CrossRefPubMedPubMedCentral

68.

Ausems MG, ten Berg K, Kroos MA, van Diggelen OP, Wevers RA, Poorthuis BJ, et al. Glycogen storage disease type II: birth prevalence agrees with predicted genotype frequency. Community Genet. 1999;2(2–3):91–6. https://doi.org/10.1159/000016192.CrossRefPubMed

69.

Martiniuk F, Chen A, Mack A, Arvanitopoulos E, Chen Y, Rom WN, et al. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet. 1998;79(1):69–72.CrossRef

70.

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(9813):335–41. https://doi.org/10.1016/s0140-6736(11)61266-x.CrossRefPubMed

71.

Ghosh PS, Zhou L. The diagnostic utility of a commercial limb-girdle muscular dystrophy gene test panel. J Clin Neuromuscul Dis. 2012;14(2):86–7. https://doi.org/10.1097/CND.0b013e31824619e9.CrossRefPubMed

72.

Correia CDC, Fontana PN, de Goes GHB, Zanoteli E. Clinical variability in 2 siblings with late-onset Pompe disease. J Clin Neuromuscul Dis. 2018;20(1):47–8. https://doi.org/10.1097/cnd.0000000000000216.CrossRefPubMed

73.

van Capelle CI, van der Meijden JC, van den Hout JM, Jaeken J, Baethmann M, Voit T, et al. Childhood Pompe disease: clinical spectrum and genotype in 31 patients. Orphanet J Rare Dis. 2016;11(1):65. https://doi.org/10.1186/s13023-016-0442-y.CrossRefPubMedPubMedCentral

74.

Wens SC, van Gelder CM, Kruijshaar ME, de Vries JM, van der Beek NA, Reuser AJ, et al. Phenotypical variation within 22 families with Pompe disease. Orphanet J Rare Dis. 2013;8:182. https://doi.org/10.1186/1750-1172-8-182.CrossRefPubMedPubMedCentral

75.

Reuser AJJ, van der Ploeg AT, Chien YH, Llerena J Jr, Abbott MA, Clemens PR, et al. GAA variants and phenotypes among 1079 patients with Pompe disease: data from the Pompe registry. Hum Mutat. 2019;40(11):2146–64. https://doi.org/10.1002/humu.23878.CrossRefPubMedPubMedCentral

76.

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4. https://doi.org/10.1001/jama.2013.281053.

Title: The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease
Authors: Jorge A. Bevilacqua
Maria del Rosario Guecaimburu Ehuletche
Abayuba Perna
Alberto Dubrovsky
Marcondes C. Franca Jr
Steven Vargas
Madhuri Hegde
Kristl G. Claeys
Volker Straub
Nadia Daba
Roberta Faria
Magali Periquet
Susan Sparks
Nathan Thibault
Roberto Araujo
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Muscular Dystrophy
Muscular Dystrophy
Pompe Disease
Published in: Orphanet Journal of Rare Diseases / Issue 1/2020
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-019-1291-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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