Sanfilippo, a disease named after the paediatrician who first described it and also known as MPSIII, is a rare and fatal syndrome. It is a genetic condition that affects the metabolism and results in severe damages to the Central Nervous System (CNS).
Individuals affected by Sanfilippo lack an enzyme necessary to break down long chains of sugar molecules called mucopolysaccharides (also known as glycosaminoglycans or GAGs). As these molecules accumulate in the cells, they start causing cellular dysfunctions, particularly in the brain.
Sanfilippo is part of a wider group of pathologies
Sanfilippo is part of the MPS (Mucopolysaccharidosis) group of diseases which fall under the Lysosomal Storage Disorders (LSDs):
The lysosome is a very small unit in the cell and contains enzymes responsible for recycling cellular materials. A Lysosomal Storage Disorder is a disease where those materials don’t get recycled correctly and accumulate in the cell, causing dysfunction.
Mucopolysaccharides (MPS) are complex sugar molecules also known as GAGs (GlycoAminoGlycans) naturally produced by the body and used in the building of bones, cartilage, skin, and tissues. As the body continuously produces these molecules, it needs to constantly recycle them.
Children with MPSIII lack an enzyme required to recycle the heparan sulfate, one of the many complex sugar molecules (the GAGs) the body needs, resulting in extra storage of these molecules in the cells. Each enzyme is coded in a specific gene: an error on that gene results in the deficient production of that enzyme.
Each Sanfilippo type corresponds to a particular enzyme that is missing; all these enzymes are required to break down the heparansulfate. Type A is the most common type and is also considered the most severe, although there is great variation in the disease progression within each type.
Sanfilippo is an autosomal recessive genetic condition
Genetic means it is inherited: children get the defective gene from both their parents who carry this genetic error as a result of a genetic mutation. Both parents must be carriers for the condition to occur with 1 chance out of 4 to inherit the disease.
Recessive means the genetic error sits on a non-dominant gene; we have two copies of each gene, so carriers of a recessive gene who have a healthy copy are unaffected. There is no way of knowing if a parent is a carrier unless there is a previous history of MPSIII in the family and genetic diagnostic is undertaken.
Autosomal means the affected gene is located on a non-sex chromosome (of the 23 pairs of chromosomes we have, 22 are autosomal). Both men and women can carry the mutated gene and boys and girls can get the disease. The genes responsible for the enzyme deficiencies in MPSIII are located on chromosome 17.
Sanfilippo is a metabolic and neuro-degenerative progressive disorder
Metabolism is the set of life-sustaining chemical transformations within the cells. These transformations are done through the actions of enzymes which act as catalysts; the missing enzyme in Sanfilippo results in a metabolic disorder.
This disorder affects primarily the Central Nervous System (CNS), resulting in brain damage. Children experience hyperactivity, sleeplessness, loss of speech and other bodily function, mental retardation, cardiac issues, seizures, loss of mobility, dementia and finally death.
Children at birth appear healthy; the first symptoms are often mild developmental delays such as speech delays and usually appear between the ages of 2 and 6. As the disease progresses, children will typically develop extreme activity and behavioural problems, and gradually lose all the abilities and skills they had acquired.
The disease progression path and speed vary significantly from one child to the next, making it particularly difficult to predict. The disease symptoms cover a wide spectrum and some children may experience some of them but not others.
The disease is often diagnosed when parents find their child missing development milestones and undertake formal assessment. Because of its rarity, the disease remains largely unknown for most medical practitioners and it may take several years before a correct diagnostic is made. It is not uncommon for families to have more than one child affected before finding out they have the disease.
The disease does not yet have a cure and only limited palliative treatment currently exists; life expectancy is around 15 years. Medical research has recently achieved promising break-throughs with real hopes for the future.
For a factsheet on Sanfilippo here.
For information on current medical research programs for Sanfilippo, please visit our Research section click here.