Mortality in patients with Sanfilippo syndrome

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.