Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison

Julie B. Eisengart, Kyle D. Rudser, Yong Xue, Paul Orchard, Weston Miller, Troy Lund, Ans Van der Ploeg, Jean Mercer, Simon Jones, Karl Eugen Mengel, Seyfullah Gökce, Nathalie Guffon, Roberto Giugliani, Carolina F.M. de Souza, Elsa G. Shapiro, Chester B. Whitley

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Purpose: Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood–brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics precludes randomized comparison of ERT with HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age. Methods: Long-term survival and neurologic outcomes were compared among three groups of patients with Hurler syndrome: 18 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated). All were followed starting before age 5 years. A sensitivity analysis restricted age of treatment below 3 years. Results: Survival was worse when comparing ERT versus HCT, and Untreated versus ERT. The cumulative incidences of hydrocephalus and cervical spinal cord compression were greater in ERT versus HCT. Findings persisted in the sensitivity analysis. Conclusion: As newborn screening widens treatment opportunity for Hurler syndrome, this examination of early treatment quantifies some ERT benefit, supports presumptions about BBB impenetrability, and aligns with current guidelines to treat with HCT.

Original languageEnglish (US)
Pages (from-to)1423-1429
Number of pages7
JournalGenetics in Medicine
Issue number11
StatePublished - Nov 1 2018

Bibliographical note

Publisher Copyright:
© 2018, American College of Medical Genetics and Genomics.


  • enzyme replacement therapy
  • hematopoietic cell transplantation
  • mucopolysaccharidosis
  • neurodegenerative
  • newborn screening


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