Sanfilippo Syndrome belongs to a group of around 50 diseases collectively named lysosomal storage disorders. It is estimated that one child in every 5,000 births will be born with a lysosomal storage disorder.
These disorders involve the build-up of toxic material inside a part of the cell called the lysosome. The lysosome is involved in waste degradation and recycling; usually, the material is broken down and recycled by enzymes inside the lysosome. Lysosomal storage disorders arise due to a deficiency of one of the many enzymes that work in this part of the cell.
Because the material cannot be broken down, it builds up and clogs up the lysosome. In Sanfilippo, the complex sugar heparan sulfate accumulates over time. It damages the neurons in the brain and other cells in the body, leading to developmental delay, autistic-like behaviours, and ultimately dementia.
In other lysosomal storage disorders, other enzymes are missing, and different types of molecules build up. This can influence which part of the body is most severely affected. In some, the main impact is on the brain, but in others, different or multiple parts of the body are affected, such as bone, joints, liver or heart.
Sanfilippo syndrome belongs to a subgroup of lysosomal storage disorders known as mucopolysaccharidoses (MPS). Some other MPS disorders can also affect the brain, such as MPS I (Hurler syndrome) and MPS II (Hunter syndrome), which predominantly affects males. Dermatan sulphate and heparan sulphate both build up in these disorders.
Alpha-mannosidosis is another type of lysosomal storage disorder that involves the build-up of a complex sugar molecule called mannose. Symptoms can be similar to Sanfilippo, including skeletal problems and intellectual disability. It’s even rarer than Sanfilippo, affecting 1 in every 500,000 people; because it’s so rare, there is little research focused on this disorder.
In almost all cases, research into a lysosomal storage disorder will directly or indirectly inform the search for treatments for other lysosomal storage disorders. This research includes treatment avenues that target inflammation or lysosomal function, or the best way to deliver genes or enzymes into cells or across the blood-brain barrier. Researchers don’t work in isolation or on isolated diseases - their findings can cross from one research field to another and from one disease to another.
The research we fund at the Sanfilippo Children’s Foundation has the potential to help not only patients with Sanfilippo, but those with other lysosomal storage disorders. Avenues like gene therapy, enzyme replacement therapy, anti-inflammatory and other types of treatment have the potential to change the lives of patients and families impacted by this group of devastating diseases.