What is San Filippo Syndrome?

The disease manifests itself when the two parents, father and mother, although healthy, are carriers of an altered gene. When both parents must contribute the mutation we speak of autosomal recessive genetic behavior.

The mucopolysaccharides They are sugars in the form of long linear chains, usually linked to proteins, forming proteoglycans. The modern terminology for mucopolysaccharides is glycosaminoglycans (GAGs).

What does it consist of

• "Muco": refers to the thick gelatinous layer of the molecules.
• "Poli": means many.
• "Saccharide": is a general term for the sugar part of the molecule.

These sugars are located on the surface and around the cells, providing viscosity to the tissues and participating in the structures of bones, cartilage, tendons, cornea, skin, connective tissue and synovial fluid (joint fluid).

In Sanfilippo syndrome, the mucopolysaccharide heparan sulfate (HS) because there is a deficit of four type enzymes hydrolases: proteins specialized in transforming complex mucopolysaccharide sugars into simpler molecules.

The heparan sulfate badly degraded, it is stored mainly at the level of the brain, causing serious and progressive degeneration and early death of the person.

There are four types of Sanfilippo syndrome: A, B, C, and D.

• Sanfilippo A syndrome is the most severe form. People with this type lack or have an altered form of the enzyme called Heparan N-sulfatase.

Who is affected and how

Sanfilippo disease owes its name to the pediatrician Silvester Sanfilippo, who as early as 1960 began to identify various types of mucopolysaccharidosis in urine.

In our country it is calculated that it affects 1 in 70,000 births And having a family history of this syndrome increases the risk of suffering from this condition.

It affects each patient differently and its progression, slower or faster, varies from one to another. Babies do not show signs of the disease, as the first symptoms appear between two and six years of age, in the form of mental impairment and behavioral disturbances with agitation and aggressiveness.

Stages of the syndrome

• The first years of life: leads to a high degree of frustration in parents. They observe that their child has a slower development than that of other children his age the same age.
• The second stage is characterized by a hyperactivity excessive, restlessness and often misconduct. Some children sleep very little at night. Language skills and comprehension gradually disappear, making it very difficult for parents to communicate with their child. Some children can never learn to use the toilet and others lose this ability.
• In the third stage, Children with Sanfilippo syndrome begin to walk more slowly. It is difficult for them to keep a steady pace and they tend to fall when running or walking. Balance gradually disappears and severe hearing loss also occurs (common in moderate to severe impairment) possibly worsened by frequent ear infections. And there is stiffness in the joints, which may not be fully extended. In the eyes, loss of peripheral vision and blindness occur

One of the common features of children with Sanfilippo disease is chronic discharge from, and sinus infections. Patients affected by the less severe variant of Sanfilippo Syndrome can have almost normal intelligence until adulthood.

Diagnosis

Laboratory diagnosis

• The finding of Heparan Sulfate in urine confirms the disease. The exact confirmation of the syndrome is carried out by measuring the enzymatic activity of the blood in fibroblasts of the patient's skin.
• Genetic advice: All parents with children affected by mucopolysaccharidosis should consider the fact before having another child. There is often a delay in diagnosing the disease and it is not uncommon for a family to have more than one affected child before obtaining a definitive diagnosis.

Diagnostic imaging

• Bone scan: alteration in bone ossification known as dysostosis multiplex
• brain: mild to moderate cortical atrophy at the beginning that becomes more severe in the final stages.

Is there treatment?

For now there's no cure, although different research studies are being done that are hopeful (Enzyme Replacement Therapy and Gene Therapy) and the only treatment available now is symptomatic.

The syndrome causes significant neurological symptoms, such as severe intellectual disability.

Most people with this syndrome live into their teenage years; some may live longer, while others with severe forms of the disease die at a younger age. Symptoms appear more severe in people with Sanfilippo syndrome type A.

• In our country, it is estimated that it affects 1 in every 70,000 births and having a family history of this syndrome increases the risk of suffering from this condition.
• Babies do not show signs of the disease, as the first symptoms appear between two and six years of age, in the form of mental deterioration and behavioral disturbances with agitation and aggression.
• At the moment, there is no cure, although different research studies are being carried out that are hopeful, and the only treatment available now is symptomatic.