Enzyme Replacement Therapy During Pregnancy in Fabry Patients

Review of Published Cases of Live Births and a New Case of a Severely Affected Female with Fabry Disease and Pre-eclampsia Complicating Pregnancy
  • Christoffer V. Madsen
  • Erik Ilsø Christensen
  • Rikke Nielsen
  • Helle Mogensen
  • Åse K. Rasmussen
  • Ulla Feldt-RasmussenEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 44)


Fabry disease (FD) is an X-linked, lysosomal storage disease. Mutations in the gene coding for alpha-galactosidase A lead to globotriaosylceramide (Gb-3) accumulation in lysosomes and in placenta and umbilical cord. Impact of FD and treatment with enzyme replacement (ERT) on foetal development is undisclosed.

A 38-year-old primigravida with FD (G85N) is reported. She has 50% reduced alpha-galactosidase A activity and elevated plasma and urine-Gb-3. She was severely affected with ischaemic stroke at age 23, hypertension, albuminuria and moderately reduced renal function. ERT was initiated at age 23 years in 2001 and continued during spontaneous pregnancy at age 38. In third trimester she developed moderate-to-severe pre-eclampsia, successfully managed by methyldopa. Chorion villus sampling revealed a male foetus without the maternal gene mutation. Planned Caesarean section was performed without complications at gestational age week 38 + 6, delivering a healthy boy. Histopathological placental examination showed no sign of Gb-3 accumulation. Literature survey disclosed a total of 12 cases, 8 were treated with ERT during pregnancy and 5 infants inherited the family mutation. All outcomes were successful. In the six cases with available placental histopathological examination, Gb-3 accumulation was only seen on the foetal side if the foetus had the inherited mutation.

In conclusion, the present case, describing the first data from a severely affected FD patient receiving ERT during pregnancy complicated by pre-eclampsia, together with all other published cases, has emphasized that ERT is safe during pregnancy and resulting in successful foetal outcome; despite this, ERT is by the health authorities advised against during pregnancy.


Alpha-galactosidase A enzyme deficiency Enzyme replacement therapy Fabry disease Lysosomal storage disease Placental examination Pre-eclampsia Pregnancy 



The patient is thanked for her kind cooperation and her willingness to help improving knowledge and management within the field of FD. The skilled assistance from technician Casper Kok and research nurse Ira Hagen Petersen is gratefully acknowledged.

Genzyme is thanked for providing the antihuman α-galactosidase A antibody. Hanne Sidelmann and Inger B. Kristoffersen are thanked for the skilful technical assistance. Mette Madsen (Dept. of Biomedicine, Aarhus University) is thanked for providing tissue from the control placenta.

Ulla Feldt-Rasmussen’s research salary is sponsored by an unrestricted research grant for NovoNordisk Foundation.


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Christoffer V. Madsen
    • 1
  • Erik Ilsø Christensen
    • 2
  • Rikke Nielsen
    • 2
  • Helle Mogensen
    • 3
  • Åse K. Rasmussen
    • 1
  • Ulla Feldt-Rasmussen
    • 1
    Email author
  1. 1.Department of Medical EndocrinologyCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
  2. 2.Department of Biomedicine, Anatomy, Section of Cell Biology, The Faculty of Health SciencesAarhus UniversityAarhusDenmark
  3. 3.Department of Gynaecology and ObstetricsKolding HospitalKoldingDenmark

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