Sanfilippo's Syndrome

WHAT:

Sanfilippo's Syndrome is the type III of a group of diseases known as the Mucopoly-saccharidoses (MPSs). MPSs are metabolic disorders. In other words, they are diseases whereby there is difficulty in breaking down macromolecules called Glycosamino-glycans (GAS), which are long chains of sugar molecules in each of our cells that help build bones, cartilages, tendons, corneas, skin, and connective tissues. The Glycosamino-glycans were originally called Mucopolysaccharides: This is the reason the diseases are called Mucopolysaccharidoses. There are 11 types of MPS based on the type of the GASs that are undegraded. Sanfillipo's Syndrome is a type of MPS in which the GASs called Heparan Sulphate are not broken down in the cells. This affects many organ systems in the body because MPSs are ubiquitous Ð'- they are omnipresent in the body. Failure of the cell to break down complex sugar chainsÐ'-the MPSsÐ'-leads to their accumulation in the cell, especially in the lysosomes. This is why MPSs are also regarded as lysosomal storage disorders.

WHY:

Sanfilippo's Syndrome is an inherited disorder of the lysosomes, which are cell organelles responsible for the production of specific enzymes needed to degrade Heparan Sulfate. In addition, it is an autosomal recessive trait, affecting males and females equally. There are four distinct types of Sanfilippo Syndrome, each caused by alteration of a different enzyme needed to completely break down the heparan sulfate sugar chain. They are Sanfilippo A, B, C, and D.

Ð'* Sanfilippo A is caused is caused by the missing or deficient enzyme heparin-N-sulfatase.

Ð'* Sanfilippo B is caused by the missing or deficient enzyme alpha-N-acetylglucosaminidase.

Ð'* Sanfilippo C is caused by missing or deficient enzyme acetyl-CoAlpha: glucosaminide-acetyltransferase.

Ð'* Sanfilippo D is caused by lack of enzyme N-acetylglucosamine-6-sulfatase.

Distinguishing the clinical effects of these diseases is not possible: they have similar symptoms. However, the symptoms of Type A are more severe and progress more rapidly than others.

SIGNS AND SYMPTOMS/CLINICAL FEATURES:

When a child is born, the affects of Sanfilippo Syndrome may not be evident, but as time goes on, the parent may start to see changes in their child. The normal age of onset for symptoms is between the ages of 2-6 ("Mucopolysaccharidoses" 3). Children affected with Sanfilippo syndrome go through three main stages of symptoms. In the first stage, the child experiences problems with mental and motor skill development. The child begins to show a decline in learning ("Mucopolysaccharidoses" 3). This is followed by an ensuing loss of language skills; some may never even learn to speak. A partial or total loss of hearing is also a symptom in the first stage ("Mucopolysaccharidoses" 3). In some cases, the symptoms associated with this stage can progress to severe mental retardation in the child (Sondheimer 1). In the second stage of syndrome, the affected child displays aggressive behavior, hyperactivity, profound dementia, and trouble sleeping for more than a few hours ("Mucopolysaccharidoses" 3). In the final stage, the child becomes increasingly unsteady on their feet and experiences a deterioration of gait. Some are unable to walk by the age of 10. ("Mucopolysaccharidoses" 3; Sondheimer 1). Some may also require the aid of a wheelchair or walking aid to get around at this stage.

Other symptoms associated with Sanfilippo syndrome are coarse facial features such as thick lips and an enlarged mouth, some form of dwarfism is also present, with the presence of short stature and a disproportionately short trunk. Skeletal irregularities such as abnormal bone shapes and/or size are also common. The child can also have an enlarged liver or spleen, short claw-like hands, joint stiffness and carpal tunnel syndrome ("Mucopolysaccharidoses" 2). Some individuals may also have heart disease from a result of an enlarged or diseased heart valves ("Mucopolysaccharidoses" 2). Additional symptoms include a narrow airway passage in the throat and enlargement of the tonsils and adenoids, which can make it difficult for the child to eat or swallow. It is also common for them to experience respiratory infections ("Mucopolysaccharidoses" 3).

WHO:

The disease manifests in young children. Due to complication of the symptoms, life-span of an infected child does not usually extend beyond late teens to early twenties. It is estimated that 1 out of 25,000-200,000 babies born worldwide will have Sanfilippo's Syndrome. It is such a rare disease, that a practicing medical doctor does not usually expect more than an average of one incident of the disease in a year. It's more prevalent in the Jewish community, specifically Ashkenazi Jews and their descendants. Furthermore, it is an autosomal recessive disorder, meaning that only individuals inheriting the defective gene from both parents are affected.

In general, the following factors contribute to an individual's risk to a genetic disease:

Ð'* A family history of a genetic disease.

Ð'* Homogenous parents: parents who are closely related or belong to the same ethnic denomination.

Ð'* Parent carrying the gene but not showing the symptoms. (MPS Fact Sheet, NINDS)

WHEN:

In 1961, Harris discovered a six-year old girl with hepatosplenomegalyÐ'-a normal skeletal surveyÐ'-and excretion of large amounts of heparin sulfate in the urine. Later, "[I] n 1962 and 1963, Sanfilppo et al described eight children with mental retardation and heparin sulfate mucopolysaccyhariduria and delineated the syndrome which now bears his name. Sanfilippo syndrome is one of