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. 2017 Oct 23;12(1):168.
doi: 10.1186/s13023-017-0717-y.

Mortality in patients with Sanfilippo syndrome

Christine Lavery  1 , Chris J Hendriksz  2 , Simon A Jones  3
Affiliations

Mortality in patients with Sanfilippo syndrome

Christine Lavery et al. Orphanet J Rare Dis. .

Abstract

Background: Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III) is an inherited monogenic lysosomal storage disorder divided into subtypes A, B, C and D. Each subtype is characterized by deficiency of a different enzyme participating in metabolism of heparan sulphate. The resultant accumulation of this substrate in bodily tissues causes various malfunctions of organs, ultimately leading to premature death. Eighty-four, 24 and 5 death certificates of patients with Sanfilippo syndrome types A, B and C, respectively, were obtained from the Society of Mucopolysaccharide Diseases (UK) to better understand the natural course of these conditions, covering the years 1977-2007.

Results: In Sanfilippo syndrome type A mean age at death (± standard deviation) was 15.22 ± 4.22 years, 18.91 ± 7.33 years for patients with Sanfilippo syndrome type B and 23.43 ± 9.47 years in Sanfilippo syndrome type C. Patients with Sanfilippo syndrome type A showed significant increase in longevity over the period of observation (p = 0.012). Survival rates of patients with Sanfilippo syndrome type B did not show a statistically significant improvement (p = 0.134). In Sanfilippo syndrome types A and B, pneumonia was identified as the leading cause of death.

Conclusions: The analysis of 113 death certificates of patients with Sanfilippo syndrome in the UK has demonstrated that the longevity has improved significantly in patients with Sanfilippo syndrome type A over a last few decades. The numbers of patients with Sanfilippo syndrome types B and C were too small to identify any significant trend changes for these groups. Respiratory tract infections, notably pneumonia, remain the leading cause of mortality in Sanfilippo syndrome types A and B. The extended lifespans of patients with Sanfilippo syndrome type A were achieved despite the lack of therapies to target the primary insult or pathophysiology of the disease. However, the mean age at death of these patients remains low when compared with the general population. Therefore, there is an urgent need for effective disease-specific therapies to be developed so that the quality of life and survival of patients with Sanfilippo syndrome can be improved.

Keywords: Mortality; Mucopolysaccharidosis; Pneumonia; Respiratory failure; Sanfilippo syndrome.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable. This article does not report on any studies with human and animal subjects performed by any of the authors.

Consent for publication

Not applicable.

Competing interests

C. Lavery serves on advisory boards for BioMarin Pharmaceutical Inc. and has received travel grants and lecture fees from BioMarin Pharmaceutical Inc.

C. J. Hendriksz serves as a director of FYMCA Medical Ltd. and consultant for Actelion, BioMarin Pharmaceutical Inc., Chiesi, Sanofi Genzyme and Shire. All of these companies have potential target therapies in this group of disorders.

S. A. Jones is a consultant for Alexion, BioMarin Pharmaceutical Inc., Sanofi Genzyme, Shire, Ultragenyx and Orchard Therapeutics.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Longevity in patients with Sanfilippo syndrome A. a Mean age at death over time of patients with Sanfilippo syndrome type A (n indicates the number of patients); b age at death by individual patient with Sanfilippo syndrome type A
Fig. 2
Fig. 2
Longevity in patients with Sanfilippo syndrome B. a Mean age at death over time of patients with Sanfilippo syndrome type B (n indicates the number of patients); b age at death by individual patient with Sanfilippo syndrome type B
Fig. 3
Fig. 3
Primary cause of death in patients with Sanfilippo syndrome types A and B. a Primary cause of death in patients with Sanfilippo syndrome A; b primary cause of death in patients with Sanfilippo syndrome B (there were no mortalities caused by central nervous system complications in this group)
See this image and copyright information in PMC

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