Very little is still known about the clinical features and natural course of Sanfilippo syndrome, also known as mucopolysaccharidosis (MPS) III, a rare disease that can significantly affect children’s development and lead to poor outcomes, a review study highlights.
The study, “Epidemiology of Sanfilippo syndrome: results of a systematic literature review,” was published in the Orphanet Journal of Rare Diseases.
MPS III is a rare genetic disorder that causes progressive neurocognitive degeneration. It can be classified into four subtypes — MPS IIIA, B, C, and D — based on the genetic defect and affected gene.
A team led by researchers at Syreon Research Institute in Budapest, Hungary, reviewed the currently available information in the literature regarding Sanfilippo syndrome.
“To our knowledge, this is the first systematic review of the scientific literature undertaken in this disease area,” the authors wrote.
From a total of 2,794 publications found in the initial search, only 46 studies had valuable information on the clinical characteristics of the disease. The studies reported data from 32 different countries, and most compared information on Sanfilippo patients with that of the general population.
Based on data from all the studies, researchers found that the lifetime risk at birth ranges from 0.17-2.35 per 100,000 live births for all four MPS III subtypes together, and from 0-1.62 per 100,000 live births for the most frequent subtype, MPS IIIA.
But these numbers also revealed a high variability in frequency estimates between studies, mostly due to different methodologies used and other confounding parameters included in the calculations, such as the type of diagnostic method used.
Three studies out of the 46 analyzed provided information on the presentation and course of MPS IIIA, which researchers used to evaluate the clinical characteristics of the disease.
Based on these data, the most common disease symptoms were found to be language delay, coarse features, abnormal behavior, and epilepsy. In most cases, the first signs of developmental delay or behavioral problems would appear around 2-3 years of age, while epilepsy and loss of walking ability were found to be later symptoms of the disease, at 7 and 10.4 years, respectively. Median age at diagnosis ranged from 3.5-7 years old.
Three studies also reported on the clinical characteristics of patients with MPS IIIB and MPS IIIC, which were very similar to MPS IIIA. In these patients, the most common symptoms were also coarse features, language delay, abnormal behavior, autistic spectrum disorder, and epilepsy.
In MPS IIIB patients, the first disease signs appeared before the age of 4 in 27% and dementia before the age of 6 in 24%. For MPS IIIC patients, 33% showed disease signs before 4 years old and 23% had dementia before they were 6 years old. Median age at diagnosis ranged from 2.5-4.9 for MPS IIIB and 4.5-19 years for MPS IIIC.
Mean age at diagnosis was between 3.1 and 8.3 years for MPS IIID. However, “no studies were identified in this literature search that included data on clinical characteristics and progression for patients with MPS IIID,” according to the researchers.
Since ages at onset varied significantly between disease subtypes and studies, the reports on life expectancy followed the same trend.
Mean survival in children with MPS IIIA, as reported by four studies, was between approximately 13 and 18 years. Patients with MPS IIIB were reported to live longer, with mean survival times between 17.1 and 19 years. For patients with MPS IIIC, the studies reported a mean survival ranging from 19-34 years.
“All 4 subtypes of MPS III are exceptionally rare genetic diseases, but they each have devastating effects on children,” the researchers wrote. “[Additional] higher-quality epidemiological data are needed to appropriately target resources” and enhance research into the development of pharmacological treatments, they suggest.