Journal of Inherited Metabolic Disease

, Volume 33, Supplement 3, pp 333–339 | Cite as

Antenatal diagnosis of pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy

  • Mohamed A. Hamdan
  • Bushra A. El-Zoabi
  • Muzibunnisa A. Begam
  • Hisham M. Mirghani
  • Mohamed H. Almalik
Research Report


Hypertrophic cardiomyopathy (HCM) affects most infants with Pompe disease (PD), and may serve as a marker for its antenatal diagnosis (ANDx) by fetal echocardiography (FE). Fetuses diagnosed with HCM between 2006 and 2009 were included in this study. HCM, defined as Z-score of mean left ventricular wall thickness (LVWT) and/or mass (LVM) above 2, was detected in 5/1,268 fetuses (0.39%) carried by 1,137 pregnant women referred for FE. Three fetuses (0.24%) had postnatal confirmation of PD. Their gestational age and fetal weight at diagnosis was (mean ± standard deviation) 31 ± 3.6 weeks and 1.9 ± 0.2 kg, respectively. Fetal Z-score of LVM and LVWT was 3.8 ± 0.9 and 3.1 ± 0.6, respectively. Postnatally, acid α-glucosidase (GAA) enzyme activity was nearly absent in all patients, 2 were homozygous for the mutation 1327-2A>G in the GAA gene, and 1 was homozygous for 340insT. Enzyme replacement therapy (ERT) was initiated 4.9 ± 7.8 days after birth (range 2 h–14 days), and continued every 2 weeks. Two infants are alive at 4 and 31 months, and one died of aspiration pneumonia at 19 months. Cardiac hypertrophy resolved after 10–12 weeks of ERT in all patients, and none required any respiratory support. One patient had normal neurodevelopmental assessment at 25 months, and one had severe global delay at 15 months before death. ANDx of PD by FE is feasible based on fetal HCM. It promotes early initiation of ERT which may improve outcome in some patients. However, larger studies and longer follow-ups are required.


Cardiac Hypertrophy Enzyme Replacement Therapy United Arab Emirate Newborn Screening Glycogen Storage Disease 


Source of funding

The authors confirm independence from any sponsor. The content of this article has not been influenced by any sponsor.

Competing interest

The first author (M.A. Hamdan) discloses limited consultation services and honorarium received from Genzyme Corp. (Cambridge, MA, USA). No financial support was received for preparing the manuscript.

Statement of Ethics

This manuscript was written in compliance with the regulations of the Human Research and Ethics Committee at our institution. Data regarding the patients’ clinical status were collected by chart review. Patients’ confidentiality was maintained during data collection and manuscript preparation.


  1. Al-Gazali L, Hamamy H, Al-Arrayad S (2006) Genetic disorders in the Arab world. BMJ 333:831–834PubMedCrossRefGoogle Scholar
  2. Allan L (2000) Antenatal diagnosis of heart disease. Heart 83:367–370PubMedCrossRefGoogle Scholar
  3. Ansong AK, Li JS, Nozik-Grayck E et al (2006) Electrocardiographic response to enzyme replacement therapy for Pompe disease. Genet Med 8:297–301PubMedCrossRefGoogle Scholar
  4. Bhat AH, Corbett V, Carpenter N et al (2004) Fetal ventricular mass determination on three-dimensional echocardiography: studies in normal fetuses and validation experiments. Circulation 110:1054–1060PubMedCrossRefGoogle Scholar
  5. Chen LR, Chen CA, Chiu SN et al (2009) Reversal of cardiac dysfunction after enzyme replacement in patients with infantile-onset Pompe disease. J Pediatr 155:271–275PubMedCrossRefGoogle Scholar
  6. Chien YH, Chiang SC, Zhang XK et al (2008) Early detection of pompe disease by newborn screening is feasible: results from the taiwan screening program. Pediatrics 122(1):e39–e45PubMedCrossRefGoogle Scholar
  7. Cuneo BF (2006) Outcome of fetal cardiac defects. Curr Opin Pediatr 18:490–496PubMedCrossRefGoogle Scholar
  8. Fesslova' V, Nava S, Villa L (1999) Evolution and long term outcome in cases with fetal diagnosis of congenital heart disease: Italian multicentre study. Fetal cardiology study group of the italian society of pediatric cardiology. Heart 82:594–599PubMedGoogle Scholar
  9. Foster BJ, Mackie AS, Mitsnefes M, Ali H, Mamber S, Colan SD (2008) A novel method of expressing left ventricular mass relative to body size in children. Circulation 117:2769–2775PubMedCrossRefGoogle Scholar
  10. Fowler DJ, Anderson G, Vellodi A, Malone M, Sebire NJ (2007) Electron microscopy of chorionic villus samples for prenatal diagnosis of lysosomal storage disorders. Ultrastruct Pathol 31:15–21PubMedCrossRefGoogle Scholar
  11. Friedman DM, Kim MY, Copel JA et al (2008) Utility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval and Dexamethasone Evaluation (PRIDE) prospective study. Circulation 117:485–493PubMedCrossRefGoogle Scholar
  12. Gardiner HM (2001) Fetal echocardiography: 20 years of progress. Heart Suppl 2: II12–22Google Scholar
  13. Gottesman GS, Hoffmann JW, Vogler C, Chen SC (1999) Hypertrophic cardiomyopathy in a newborn infant. J Pediatr 134:114–118PubMedCrossRefGoogle Scholar
  14. Hamdan MA, Almalik MH, Mirghani HM (2008) Early administration of enzyme replacement therapy for Pompe disease: short-term follow-up results. J Inherit Metab Dis [Epub ahead of print]Google Scholar
  15. Hirschhorn R, Reuser AJJ (2001) Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, (eds); Childs B, Kinzler KW, Vogelstein B (assoc eds). The metabolic and molecular bases of inherited diseases, 8th edn. McGraw Hill, New York, 3389–3420Google Scholar
  16. Howell RR, Byrne B, Darras BT, Kishnani P, Nicolino M, van der Ploeg A (2006) Diagnostic challenges for Pompe disease: an under-recognized cause of floppy baby syndrome. Genet Med 8:289–296PubMedCrossRefGoogle Scholar
  17. Hug G, Soukup S, Ryan M, Chuck G (1984) Rapid prenatal diagnosis of glycogen-storage disease type II by electron microscopy of uncultured amniotic-fluid cells. N Engl J Med 310:1018–1022PubMedCrossRefGoogle Scholar
  18. Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D (2006a) Infantile-onset pompe disease natural history study group. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 148:671–676PubMedCrossRefGoogle Scholar
  19. Kishnani PS, Steiner RD, Bali D et al (2006b) Pompe disease diagnosis and management guideline. Genet Med 8:267–288PubMedCrossRefGoogle Scholar
  20. Kishnani PS, Corzo D, Nicolino M et al (2007) Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology 68:99–109PubMedCrossRefGoogle Scholar
  21. Kishnani PS, Corzo D, Leslie ND et al (2009) Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res 66:329–335PubMedCrossRefGoogle Scholar
  22. Kishnani PS, Goldenberg PC, DeArmey SL et al (2010) Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab 99:26–33PubMedCrossRefGoogle Scholar
  23. Kleijer WJ, van der Kraan M, Kroos MA et al (1995) Prenatal diagnosis of glycogen storage disease type II: enzyme assay or mutation analysis? Pediatr Res 38:103–106PubMedCrossRefGoogle Scholar
  24. Kroos M, Pomponio RJ, van Vliet L et al (2008) Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Hum Mutat 29:E13–E26PubMedCrossRefGoogle Scholar
  25. Lee W, Allan L, Carvalho JS et al (2008) ISUOG consensus statement: what constitutes a fetal echocardiogram? Ultrasound Obstet Gynecol 32:239–242PubMedCrossRefGoogle Scholar
  26. Levine JC, Kishnani PS, Chen YT, Herlong JR, Li JS (2008) Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease. Pediatr Cardiol 29:1033–1042PubMedCrossRefGoogle Scholar
  27. Millaire M, Bujold E, Morency AM, Gauthier RJ (2006) Mid-trimester genetic amniocentesis in twin pregnancy and the risk of fetal loss. J Obstet Gynaecol Can 28:512–518PubMedGoogle Scholar
  28. Odibo AO, Gray DL, Dicke JM, Stamilio DM, Macones GA, Crane JP (2008) Revisiting the fetal loss rate after second-trimester genetic amniocentesis: a single center's 16-year experience. Obstet Gynecol 111:589–595PubMedCrossRefGoogle Scholar
  29. Pedra SR, Smallhorn JF, Ryan G et al (2002) Fetal cardiomyopathies: pathogenic mechanisms, hemodynamic findings, and clinical outcome. Circulation 106:585–591PubMedCrossRefGoogle Scholar
  30. Phupong V, Shuangshoti S, Sutthiruangwong P, Maneesri S, Nuayboonma P, Shotelersuk V (2005) Prenatal diagnosis of Pompe disease by electron microscopy. Arch Gynecol Obstet 271:259–261PubMedGoogle Scholar
  31. Schneider C, McCrindle BW, Carvalho JS, Hornberger LK, McCarthy KP, Daubeney PE (2005) Development of Z-scores for fetal cardiac dimensions from echocardiography. Ultrasound Obstet Gynecol 26:599–605PubMedCrossRefGoogle Scholar
  32. Van den Hout HM, Hop W, van Diggelen OP et al (2003) The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature. Pediatrics 112:332–340PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Mohamed A. Hamdan
    • 1
  • Bushra A. El-Zoabi
    • 1
  • Muzibunnisa A. Begam
    • 2
  • Hisham M. Mirghani
    • 3
  • Mohamed H. Almalik
    • 1
  1. 1.Department of PediatricsTawam HospitalAl Ain, Abu DhabiUnited Arab Emirates
  2. 2.Department of Obstetrics and GynecologyTawam HospitalAl Ain, Abu DhabiUnited Arab Emirates
  3. 3.Department of Obstetrics and Gynecology, Faculty of Medicine and Health SciencesUAE UniversityAl Ain, Abu DhabiUnited Arab Emirates

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