http://www.raredr.com/news/mortality-sanfilippo
Exploring Mortality Rates in Sanfilippo Syndrome Patients

James Radke

This week in the Orphanet Journal of Rare Diseases, Christine Lavery of the Society of Mucopolysaccharide Diseases and colleagues published the latest mortality data for patients with Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III).1 

While the data indicates some progress in being made in how long these patients survive, the reality is that most are still dying at fairly young ages ranging from 15 to 23 years, depending on the subtype. As new treatments begin to emerge, including the possibility of gene therapy, the community is hopeful that mortality data will significantly improve in the next few years.

Sanfilippo syndrome is a lysosomal disease in which there are inadequate levels of the enzymes necessary to metabolize heparan sulfate properly. There is a build-up of heparan sulfate that occurs which in leads to progressive neural degeneration.

There are 4 types of Sanfilippo syndrome based on the specific enzyme that is affected. The respective symptoms for each of the 4 subtypes are slightly different, but in general, these children begin life with a very healthy appearance, and shortly thereafter begin to show symptoms such as hyperactivity, speech delays, and ‘autistic-like’ behavior that are often dismissed. As the disease progresses, symptoms will become more pronounced and the children will begin to lose their ability to speak, walk, and eat.

Since each of the subtypes is associated with a specific enzyme, it is important that the natural history for each subtype is understood. To that end, Lavery’s team examined the mortality of the different subtypes using data obtained from the Society of Mucopolysaccharide Diseases (UK).

In total, 113 deaths were reported in the years 1977 – 2007. Most were for patients with Sanfilippo type AA (n=84), followed by type B (n=24) and type C (n=5). 

Over a 30-year span of collected data, the mean ages of death for the 3 subtypes were: Examination of the age of death over time shows that these young adults are living significantly longer now than they were 3 decades ago, despite the fact that no treatments have become available.

As shown in Figures 1 and 2, the age of death rose for both Sanfilippo A and B over the years. Not enough data is currently available for patients with Sanfilippo C to state there is an improvement but the authors did note that

Figure: Age of death for Sanfilippo Type A Patients




Figure: Age of death for Sanfilippo Type A Patients




The most common cause of death reported in both Samfillipo Type A and B was pneumonia, as shown in Figure 3a (Sanfilippo type A) and Figure 3b (Sanfilippo type B). Cardiorespiratory failure, gastrointestinal complications, central nervous system complications and other causes were responsible for the remainder of the deaths.

Figure 3: Cause of Death in Sanfilippo Type A and Sanfilippo Type B




The authors of the study noted that their results are similar to other studies performed elsewhere, including those in Spain, Sweden, and the United States.2-4 Interestingly, reports from the Netherlands have shown patients with Sanfilippo type B to live much longer (mean age of death = 43 years).5 

It was also noted that while the primary cause of death in Sanfilippo patients is pneumonia, the proportion of patients dying from pneumonia has decreased over time and may reflect improvements in respiratory care.

References
  1. Lavery C, Hendriksz CJ, Jones SA. Mortality in patients with Sanfilippo syndrome Orphanet J  Rare Dis 2017;12:168. 
  2. Delgadillo V, del Mar O'Callaghan M, Gort L, Coll MJ, Pineda M. Natural history of Sanfilippo syndrome in Spain. Orphanet J Rare Dis. 2013;8189
  3. Malm G, Mansson JE. Mucopolysaccharidosis type III (Sanfilippo disease) in Sweden: clinical presentation of 22 children diagnosed during a 30-year period. Acta Paediatr. 2010;998:1253–7.
  4. Buhrman D, Thakkar K, Poe M, Escolar ML. Natural history of Sanfilippo syndrome type a. J Inherit Metab Dis. 2014;373:431–7.
  5. Valstar MJ, Bruggenwirth HT, Olmer R, Wevers RA, Verheijen FW, Poorthuis BJ, et al. Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype. J Inherit Metab Dis. 2010;336:759–67.
 
Figures obtained from open source article, Lavery et al. Orphanet J  Rare Dis 2017;12:168.
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