Download PDF
Journal of Pediatric Neurology 2024; 22(01): 037-043
DOI: 10.1055/s-0043-57241
Original Article

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

Tuhina Nagpal
1   SR Pediatric Gastroenterology, SGPGI, Lucknow, Uttar Pradesh, India
,
Manisha Goyal
2   Department of Pediatrics, SMS Medical College, Jaipur, Rajasthan, India
,
Priyanshu Mathur
2   Department of Pediatrics, SMS Medical College, Jaipur, Rajasthan, India
,
Kamlesh Kumar Agrawal 
2   Department of Pediatrics, SMS Medical College, Jaipur, Rajasthan, India
,
Ashok Gupta
2   Department of Pediatrics, SMS Medical College, Jaipur, Rajasthan, India
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

A high index of suspicion is required to diagnose rare genetic disorders, such as Pompe disease, with common clinical manifestations in children. There is a need to sensitize physicians regarding cues to early screening and diagnosis of such patients. Minimal epidemiological data are available on Pompe disease in India. The aim of this study was to determine the prevalence of Pompe disease in high-risk pediatric populations and determine the appropriateness of screening dried blood spot (DBS) tests to facilitate the diagnosis of Pompe disease. We screened pediatric patients presented with (1) unexplained hypotonia, respiratory distress, cardiomyopathy, and elevated liver function tests; and (2) unexplained limb girdle muscle weakness through a DBS test for enzyme assay. Those patients found positive underwent acid alpha-glucosidase mutational analysis. This prospective cross-sectional study was conducted in 45 suspected patients after approval from the institutional ethical committee. Of the 45 suspected patients, 9 (20%) were found to be positive by DBS test. Out of these nine tested, four (44.4%) were positive, two (22.2%) were negative, and three (33.3%) could not be tested for mutation analysis. The prevalence of genetically confirmed Pompe disease in high-risk populations was 8.8%. The results of this study show that clinical suspicion and DBS filter paper test facilitate early diagnosis and management, thereby improving the quality of life in patients. DBS test acts as a robust, rapid first-tier screening test for Pompe disease.

Keywords

Pompe disease - alpha-glucosidase - hypotonia - cardiomyopathy - dried blood spot test

Ethical Approval

This study is approved by the Ethical Committee of SMS Medical College and attached hospitals.


Consent to Participate

Written informed permission was obtained from the parents.


Consent for Publication

The authors affirm that human research participants provided informed consent for publication.




Publication History

Received: 11 November 2022

Accepted: 22 March 2023

Article published online:
05 June 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Hers HG. alpha-Glucosidase deficiency in generalized glycogenstorage disease (Pompe's disease). Biochem J 1963; 86 (01) 11-16
    CrossrefPubMedGoogle Scholar
  • 2 De Duve C. The lysosome. Sci Am 1963; 208: 64-72
    CrossrefPubMedGoogle Scholar
  • 3 Raju U, Shaw SC, Rana KS, Sharma M, Ramamurthy HR. Pompe's disease in childhood: a metabolic myopathy. Med J Armed Forces India 2010; 66 (01) 32-36
    CrossrefPubMedGoogle Scholar
  • 4 Chien Y-H, Hwu WL, Lee NC. Pompe disease: early diagnosis and early treatment make a difference. Pediatr Neonatol 2013; 54 (04) 219-227
    CrossrefPubMedGoogle Scholar
  • 5 Hirschhorn R, Reuser AJJ. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Beaudet A, Scriver C, Sly W. , et al, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2001: 3389-3420
    Google Scholar
  • 6 Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D. Infantile-Onset Pompe Disease Natural History Study Group. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006; 148 (05) 671-676
    CrossrefPubMedGoogle Scholar
  • 7 Hagemans ML, Winkel LP, Van Doorn PA. et al. Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. Brain 2005; 128 (Pt 3): 671-677
    CrossrefPubMedGoogle Scholar
  • 8 Verma J, Thomas DC, Kasper DC. et al. Inherited metabolic disorders: efficacy of enzyme assays on dried blood spots for the diagnosis of lysosomal storage disorders. JIMD Rep 2017; 31: 15-27
    CrossrefPubMedGoogle Scholar
  • 9 Tang H, Feuchtbaum L, Sciortino S. et al. The first year experience of newborn screening for Pompe disease in California. Int J Neonatal Screen 2020; 6 (01) 9
    CrossrefPubMedGoogle Scholar
  • 10 Thuriot F, Gravel E, Hodson K. et al. Molecular diagnosis of Pompe disease in the genomic era: correlation with acid alpha-glucosidase activity in dried blood spots. J Clin Med 2021; 10 (17) 3868
    CrossrefPubMedGoogle Scholar
  • 11 Niño MY, Wijgerde M, de Faria DOS. et al. Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience. Eur J Hum Genet 2021; 29 (03) 434-446
    CrossrefPubMedGoogle Scholar
  • 12 Kishnani PS, Howell RR. Pompe disease in infants and children. J Pediatr 2004; 144 (05) S35-S43
    CrossrefPubMedGoogle Scholar
  • 13 van den Hout HM, Hop W, van Diggelen OP. et al. The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature. Pediatrics 2003; 112 (02) 332-340
    CrossrefPubMedGoogle Scholar
  • 14 Gupta N, Kazi ZB, Nampoothiri S. et al. Clinical and molecular disease spectrum and outcomes in patients with infantile-onset Pompe disease. J Pediatr 2020; 216: 44-50.e5
    CrossrefPubMedGoogle Scholar
  • 15 Yang CF, Liu HC, Hsu TR. et al. A large-scale nationwide newborn screening program for Pompe disease in Taiwan: towards effective diagnosis and treatment. Am J Med Genet A 2014; 164A (01) 54-61
    CrossrefPubMedGoogle Scholar
  • 16 van Capelle CI, van der Meijden JC, van den Hout JM. et al. Childhood Pompe disease: clinical spectrum and genotype in 31 patients. Orphanet J Rare Dis 2016; 11 (01) 65
    CrossrefPubMedGoogle Scholar
  • 17 Cabello JF, Marsden D. Pompe disease: clinical perspectives. Orphan Drugs Res Rev 2017; 7: 1-10
    CrossrefPubMedGoogle Scholar
  • 18 Winchester B, Bali D, Bodamer OA. et al; Pompe Disease Diagnostic Working Group. Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report from an international consensus meeting. Mol Genet Metab 2008; 93 (03) 275-281
    CrossrefPubMedGoogle Scholar
  • 19 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): 397-398
    CrossrefPubMedGoogle Scholar
  • 20 Amalfitano A, Bengur AR, Morse RP. 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 (02) 132-138
    PubMedGoogle Scholar
  • 21 Kishnani PS, Corzo D, Nicolino M. et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology 2007; 68 (02) 99-109
    CrossrefPubMedGoogle Scholar
  • 22 Klinge L, Straub V, Neudorf U. 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 (01) 24-31
    CrossrefPubMedGoogle Scholar
  • 23 Bembi B, Cerini E, Danesino C. et al. Management and treatment of glycogenosis type II. Neurology 2008; 71 (23, Suppl 2): S12-S36
    CrossrefPubMedGoogle Scholar
  • 24 Slonim AE, Bulone L, Goldberg T. et al. Modification of the natural history of adult-onset acid maltase deficiency by nutrition and exercise therapy. Muscle Nerve 2007; 35 (01) 70-77
    CrossrefPubMedGoogle Scholar
  • 25 Borie-Guichot M, Tran ML, Génisson Y, Ballereau S, Dehoux C. Pharmacological Chaperone Therapy for Pompe Disease. Molecules 2021; Nov 29; 26 (23) 7223
    CrossrefPubMedGoogle Scholar
  • 26 Okumiya T, Kroos MA, Vliet LV, Takeuchi H, Van der Ploeg AT, Reuser AJ. Chemical chaperones improve transport and enhance stability of mutant alpha-glucosidases in glycogen storage disease type II. Mol Genet Metab 2007; 90 (01) 49-57
    CrossrefPubMedGoogle Scholar
  • 27 Tajima Y, Saito S, Ohno K, Tsukimura T, Tsujino S, Sakuraba H. Biochemical and structural study on a S529V mutant acid α-glucosidase responsive to pharmacological chaperones. J Hum Genet 2011; 56 (06) 440-446
    CrossrefPubMedGoogle Scholar
  • 28 Katzin LW, Amato AA. Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy. J Clin Neuromuscul Dis 2008; 9 (04) 421-431
    CrossrefPubMedGoogle Scholar
  • 29 Hug G. Enzyme therapy and prenatal diagnosis in glycogenosis type II. Am J Dis Child 1974; 128 (05) 607-609
    PubMedGoogle Scholar
  • 30 Kemper AR, Hwu WL, Lloyd-Puryear M, Kishnani PS. Newborn screening for Pompe disease: synthesis of the evidence and development of screening recommendations. Paediatrics. 2007; 120 (05) e1327-e1334
    CrossrefPubMedGoogle Scholar