Because of a Single Missing Enzyme
Individuals affected by Sanfilippo Syndrome lack a single enzyme necessary to break down long chains of sugar molecules called mucopolysaccharides (also known as glycosaminoglycans or GAGs).
As these molecules accumulate in the children’s cells, the cellular machinery cannot work properly. Once enough of the toxic GAGs build up, the cells die and vital brain tissue is lost.
Sanfilippo is a progressive, neuro-degenerative, metabolic disorder.
Metabolism consists of a set of life-sustaining chemical reactions that are constantly occurring in all of our cells. Many of these reactions rely on enzymes to break down and process the substances our body use to stay healthy – like sugars, proteins, vitamins, and fats.
In Sanfilippo Syndrome, the body does not have enough of the necessary enzymes to break down a special sugar called “heparan sulfate.”
It is important that heparan sulfate stays at just the right balance in the body. When it cannot be broken down properly, too much builds up and leads to toxic effects in the cells of the brain and body.
There are four types of Sanfilippo: Type A, B, C, and D.
Each Sanfilippo subtype corresponds to a particular enzyme that is missing in the pathway that breaks down heparan sulfate. Type A is the most common form, making up more than half of the cases. Sanfilippo Type B and Type C are less common, with Type D being the rarest form.
There can be significant variations in how quickly the disease progresses in each child, regardless of which subtype of the disease they have. Generally, children who are symptomatic and diagnosed in the preschool years display a classic, severe progression of Sanfilippo’s effects. There are extremely rare instances where a child might not become symptomatic until they are teens or adults, and this is sometimes referred to as an “Attenuated” form of the disease, with a much slower progression.
Sanfilippo is an autosomal recessive genetic condition.
A genetic condition is one that is inherited (or passed down) from parents to child. For a child to have Sanfilippo Syndrome, they must have inherited one copy of the abnormal gene from EACH parent. Parents who carry one copy of the abnormal gene are called “Carriers.” This means that they are healthy, but silently “carry” the abnormal gene in their DNA.
Both boys and girls have an equal chance of having Sanfilippo Syndrome since the affected gene is not on the “sex” (X or Y) chromosome. Every person has 23 pairs of chromosomes, 22 of which are “autosomal,” meaning they do not determine your gender. Therefore, Sanfilippo is considered an autosomal condition.
A recessive condition like Sanfilippo requires two copies of the abnormal gene to cause the disease, one from each parent. Since Sanfilippo is a recessive condition, both likely-unknowing “Carrier” parents must pass their abnormal gene to the child for the disease to occur. If both parents are “Carriers” of an abnormal Sanfilippo gene, with each pregnancy, there is a 25% chance that the child will have the disease.
Sanfilippo is part of the MPS group of diseases.
MPS (Mucopolysaccharidosis) diseases are a part of the broader category of Lysosomal Storage Disorders (LSDs). The lysosome is a very small, but important, compartment in each cell. Enzymes in the lysosome are responsible for breaking down cellular material for recycling. A Lysosomal Storage Disorder is a disease where cellular materials doesn’t get recycled properly and instead accumulate in the cell, causing irreparable damage.
Mucopolysaccharides (MPS) are complex sugar molecules also known as GAGs (glycoaminoglycans) that are naturally produced by the body and used in the communication between cells, in blood clotting, and in the building of connective tissue, nerve tissue, and skin. As the body continuously produces these molecules, it also needs to continuously break them down after they are used.
Children with Sanfilippo Syndrome lack an enzyme required to break down the specific glycosoaminoglycan (GAG) called “heparan sulfate.”