Sanfilippo Syndrome, an autosomal recessive disorder due to absent or defective enzymes, requires multidisciplinary treatment to enhance patients’ lives.
Sanfilippo Syndrome, also referred to as Mucopolysaccharidosis Type III or MPS III, is an inherited, autosomal recessive and possibly fatal disorder that involves the metabolism. When a person suffers from the disease, their body is unable to break down long chains of glycosaminoglycans properly. There are four types of MPS III, depending on the defective or missing enzyme needed for proper breakdown of the said chains of sugar molecules. There is currently no known cure for the disease, but treatment and clinical management procedures can be employed as supportive measures to help maintain and further enhance the life quality of patients.
Causes and types of MPS III
Glycosaminoglycans or mucopolysaccharides are long sugar molecule chains involved in the building of tendons, cartilage, bones and several other tissues. Normally, there is an ongoing process of building new glycosaminoglycans and breaking down the old ones, and the recycling process requires the involvement of enzymes. A person who suffers from the disease is deficient in a particular enzyme tasked to break down old glycosaminoglycans. The absence or defective state of the enzyme causes long chains of sugar molecules to remain inside the cell portion called lysosomes causing lysosomes to swell and disrupt cell functionality.
The four types of MPS III are:
- Sanfilippo Type A is the most severe among the subtypes, in which the patient is missing or has a defective enzyme known as heraparan N-sulfatase.
- Sanfilippo Type B occurs due to the absence or lack of alpha-N-acetylglucosaminidase
- Sanfilippo Type C occurs due to the absence or lack of acetyl-CoAlpha-glucosaminide acetyltransferase.
- Sanfilippo Type D occurs due to the absence or lack of N-acetylglucosamine 6-sulfatase.
No significant clinical differences arise between the various subtypes. Still, there have been instances wherein the onset of Sanfilippo Type B occurred at the latter part of a person’s life, such as during adulthood.
Sanfilippo Syndrome is an autosomal recessive disorder, which entails both parents to be carriers of the defective gene in order to both pass on the same gene to their offspring. There is a 25 percent chance for both carrier parents to have an affected child with each pregnancy. A child has a 50 percent chance of merely being a carrier through acquiring only one copy of the gene. With the last 25 percent, the child will neither become a carrier nor suffer from the disease.
Because of the inheritance pattern of MPS III, those who have had a history of the disease’s occurrence within their families are encouraged to undergo testing along with their respective partners before conceiving children.
Symptoms and diagnosis
Symptoms of MPS III immediately appear after reaching the age of one, including a gradual decline of learning capacities between the 2nd to 6th year of the child’s life. While his growth may be deemed to be normal within the first early years, the child will be below average in terms of his final height. Other symptoms of the disease include behavioral problems, full lips, diarrhea and difficulties in sleeping and walking.
Tools used for diagnosis include an intensive physical examination to detect signs of liver swelling or spleen, eye examination and neurological testing towards people with signs of seiures and mental status decline. Urine testing may also be undertaken, and the urine of those who have the disease have large amounts of mucopolysaccharide. Other tools include using echocardiogram, bone x-rays, slit lamp eye exam, blood culture and skin fibroblast culture.
Because no cure exists, the available treatment methods are used to improve the patient’s life. The variety of symptoms associated with MPS III necessitate a holistic, interdisciplinary approach. Management and treatment include consultation and continuous health care services provided by ophthalmologists, audiologists, pediatric neurologists, gastroenterologists, cardiologists, and orthopedists. Drug therapy is merely employed for the treatment of symptoms, and it does not currently belong to standard care procedures. Gene therapy for the treatment of MPS III Type B is currently being investigated in France and the US, through employing animals as models for research ventures.
There are automatically excluded therapy options for those who suffer from the disease, such as bone marrow transplantation and enzyme replacement therapy. BMT has been proven to yield positive benefits in relation to other types of Mucopolysaccharidosis disorders, but not with MPS III. ERT has also been shown to fall short in terms of improving prognosis, although direct enzyme injections to the central nervous system are currently under investigation.