Sanfilippo syndrome is a rare and intractable neurodegenerative disorder of genetic origin. The first symptoms occur during infancy and lead to premature death in early adulthood. Affected children present mental retardation and physical disabilities that worsen as the disease progresses.
The disease itself
The first symptoms of the disease - hyperactivity, sleep disorders and sudden involuntary movements - appear between the ages of 3 and 6 years. Neurological damages subsequently cause intellectual deficiencies and reduced motor skills, leading to a loss of autonomy around 10 years. There is also slight facial dysmorphia. Progressive neurodegeneration causes premature death between the ages of 20 and 30.
Sanfilippo syndrome is under-diagnosed, which makes it difficult to appreciate prevalence. However, the most recent figures estimate the number of affected births between 1 and 3 per 100,000, depending on the country. A French study carried out between 1990 and 2006 indicates 0.68 diagnosed cases per 100,000 births.
Four Sanfilippo sub-types are recognized, known as A, B, C and D. Each corresponds to a different enzyme deficiency. According to European studies to date, sub-type A is more predominant in Northern Europe, while B is more prevalent in the south.
The severity and progression of the symptoms vary according to the sub-type diagnosed. Transmission of the disease is the same for all sub-types. Known as recessive autosomic transmission, it occurs from parent to child: a child has a risk of being affected if both parents carry one of the genetic mutations responsible for the disease.
Treatment and management
At the Institut Pasteur
The Neuroscience Department houses the Institut Pasteur/Inserm “Biotherapies for neurodegenerative diseases” joint unit, which conducts research focusing on a number of neurodegenerative diseases. In July 2011 this unit, led by Jean-Michel Heard, developed the first human neuron model for Sanfilippo syndrome derived from induced pluripotent stem cells. This model is the tool of choice for studying the cellular mechanisms at the root of this disease and for identifying therapeutic options. The procedure used by the scientistscould also be applied to model other diseases neurodegenerative diseases.
The Institut Pasteur is also promoting a gene therapy trial. This trial has started in October 2013, and focuses on sub-type B of the disease.