Sanfilippo Syndrome

What is Sanfilippo Syndrome?

Sanfilippo syndrome occurs when enzymes that are needed to break down the heparan sulphate sugar chain are either defective or missing entirely. It is a rare and catastrophic genetic disorder that falls within broader group known as Liposomal Storage diseases. These diseases share an enzymatic defect that causes an accumulation of material within cells of the body. The consequences vary greatly among subgroups, ranging from mild impact with normal life expectancy to severe and terminal outcome. One of the doctors who first described the condition in 1963 was Dr.Sylvester Sanfilippo.

Sanfilippo Syndrome

The children who afflict with Sanfilippo Syndrome miss an essential enzyme that breaks down strings of complex body sugar called heparin sulphate. Partially broken-down sugar or mucopolysaccharide accumulates in brain and body’s cells and tissue cause progressive damage. And the storage process affects children’s appearances, bodily functions and development. All children with Sanfilippo tend to look alike and have similar health problems. (7)

Sanfilippo Syndrome genetics 3

Genetic Study of Sanfilippo Syndrome

Signs & Symptoms

A Sanfilippo child appears to be normal at birth. But as more and more cells become damaged symptoms begin to appear.

The build-up of muccopolysaccharides may cause

  • Hyperactivity
  • Diarrhea
  • Full lips
  • Walking problems
  • Stiff joints that may not extend fully
  • Sleep disorders
  • Loss of speech
  • Mental retardation
  • Dementia
  • Death

Sanfilippo Syndrome symptoms 4

Source –

What happens to a child with Sanfilippo Syndrome?

Sanfilippo is a type of an insidious disease that often goes undetected for years. Most of the children are born with no visible signs that anything is wrong. It’s not until the preschool years that children start to show delays or deformities. The disease is often misdiagnosed. Highly specialized and focused testing must be done in order to diagnose Sanfilippo. (6)

Sanfilippo is progressive and can be broken down into three stages.

Sanfilippo Disease pathogenesis progression Stages


The affected child with Sanfilippo will display mild facial abnormalities, delayed speech and behavioural issues. Some children

  • exhibit a large head
  • prominent forehead
  • thick skin
  • short neck
  • full lips
  • low nasal bridge
  • full round bellies
  • sinus and ear infections
  • diarrhea
  • coarse thick hair
  • tight Achilles tendons
  • low thick ears
  • bushy eyebrows
  • facial features as coarse

The sufferers may have cavities or chipped teeth from weak enamel and headaches from accumulated fluid pressure.  Minor bone deformities like raised sternum and flared ribs are quite common.  Due to a skull deformity children have large head circumferences which is clinically called J Shaped Sella Turcica.  The problems associated are vast and vary. (2), (5)


The affected child will become suffer

  • Sleeplessness
  • Restless
  • Laughing fits
  • Laughing fits
  • Grab at people or items
  • Extremely active
  • Inconsolable behaviour
  • Seizures
  • Exhibit difficult behavior
  • A sensory processing disorder like compelled to chew on things
  • Temper tantrums
  • Visual and hearing problems
  • Screaming for no apparent reason

These symptoms vary from child to child. Over time, speech loss occurs. Communication skills decline along with cognitive regression and loss of motor skills.


At this stage the disease will take its ultimate toll. The child will lose ability to walk, talk and eat on his own. While his body shuts down. As early as at the age of three deaths may occur. There are cases that live into their early teens and with some surviving into their twenties. A few cases of those with a mild form of Sanfilippo have lived into their early thirties. (7)


Four different enzymes deficiencies have been found to cause Sanfilippo. They are described as type A, B, C, or D. There is very little difference between the four types.

They are:

  1. Sanfilippo Type A: heparan N-sulfatase— Estimated incident rate is 1 in 100,000 live births.
  2. Sanfilippo Type B: alpha-N-acetylglucosaminidase— Estimated incident rate is 1 in 200,000 live births.
  3. Sanfilippo Type C: acetyl-CoAlpha-glucosaminide acetyltransferase— Estimated incident rate is 1 in 1,400,000.
  4. Sanfilippo Type D: N-acetylglucosamine 6-sulfatase— Estimated incident rate is 1 in 1,100,000.

The syndrome present is approximately 1 in 70,000 births among the four types of Sanfilippo.Parents, both of whom must carry the defective gene, have 25% chance of conceiving an affected child, 25% chance of conceiving a normal unaffected child and 50% chance of conceiving a child who is carrier like the parents.

Sanfilippo occurs 1 in 24,000 births. Based on this estimation there are approximately 200 children born with this disorder in United States every year. There are most probably thousands of families dealing with this in USA alone. Sanfilippo does not appear to be more prevalent in one geographic area or in particular ethnic group. These numbers increase to thousands births and tens of thousands living throughout the world. (3), (4)

How to diagnose Sanfilippo syndrome?

Diagnosis of the disease is usually reached within the first few years when a child does not develop as they might be expected to or they start to experience losses in developmental achievements.

It is usually identified as an inherited disorder. The parents of the child with the syndrome may not have the syndrome; they each have a recessive gene for it. This gene is passed to their child which is referred to as an autosomal recessive inheritance pattern. People who are aware that someone in their family has Sanfilippo syndrome including cousins, aunts or uncles should consider testing with their partner before conceiving a child.

Both of the parents need to have the gene for Sanfilippo syndrome in order to pass to a child. Even if one parent has Sanfilippo syndrome, it should be noted that the next generation of such children needs to be aware that they might carry the recessive gene. Sanfilippo syndrome progresses can be determined by the type of the syndrome involved whether A, B, C, or D. Each one of the types represents a lack of a particular enzyme. Among the types, type a is considered to be the most common and severe. (1), (7)

Examinations for Sanfilippo

  • Physical examination — spleen or liver swelling
  • Eye examination — clear corneas
  • Neurological testing — mental retardation and seizures
  • Urine testing —large amounts of mucopolysaccharide (heparin sulphate)

Additional testing

Additional testing related to Sanfilippo syndrome can include:

  • Blood culture
  • Slit lamp eye exam
  • Echocardiogram
  • Skin fibroblast culture
  • X-rays of the bones (1),(2),(7)

Treatment for Sanfilippo

Currently there is no cure for Sanfilippo syndrome. People with this syndrome and their family members can find support from physical therapists, occupational therapists, and doctors. Some medical treatments can help to ease some of the conditions. Caregivers will also need support along with the other children in the family who do not have the disease. Behavioral issues can be problematic for the entire family.

Children diagnosed with Sanfilippo syndrome often live short lives. New treatments in gene and stem cell therapies that are in development could be a treatable condition. Complications of the syndrome can include mental retardation, blindness, nerve damage that slowly worsens and eventually requires wheelchair use and seizure activity. Individuals affected by the syndrome can have I.Q.’s below 50.

There is no specific treatment available for Sanfilippo syndrome. (7),(5)


Genetic counselling is recommended for parents with a family history of Sanfilippo syndrome and also families who have a child with Sanfilippo syndrome. This counselling helps to understand the condition and possible treatments. Prenatal testing is also available. (1)


Currently Sanfilippo is not a disease that is curable. It tends to be fatal before the age of twenty years, although there are a few exceptions. In most cases, treatment is limited to controlling or reducing the symptoms of this disorder by making sure that cardiologists, neurologists, ophthalmologists, orthopedicians, ENTs, dentists and genetic counsellors are consulted routinely.

An Anti-convulsing medication may control seizures. Devices can be inserted in mouth to assist swallowing. And wheelchairs are required often as the disorder progresses to its immobile and final stage. Genetic counselling is encouraged. Controlling of diet can be helpful – for example, removing dairy and gluten products to help reduce mucus secretions. Early Intervention services such as Speech, Physical Therapy and Occupational Therapy are also very beneficial for the children affected with Sanfilippo syndrome. (6), (7) Life expectancy for a child with Sanfilippo Syndrome is between 12 to 20 years. (1), (7)


Sanfilippo Syndrome 2



  1. Jin, Y.; Wu, H.; Cohen, EM.; Wei, J.; Jin, H.; Prentice, H.; Wu, JY. (Mar 2007). “Genistein and daidzein induce neurotoxicity at high concentrations in primary rat neuronal cultures”. J Biomed Sci. 14 (2): 275–84
  2. Marlies J. Valstar; Hennie T. Bruggenwirth; Renske Olmer; Ron A. Wevers; Frans W. Verheijen; et al. (September 2010).
  3. Meikle PJ, Hopwood JJ, Clague AE, Carey WF (January 1999). “Prevalence of lysosomal storage disorders”. JAMA. 281 (3): 249–54.
  4. Nelson J (December 1997). “Incidence of the mucopolysaccharidoses in Northern Ireland”. Hum. Genet. 101 (3): 355–8.
  5. Piotrowska, E.; Jakóbkiewicz-Banecka, J.; Barańska, S.; Tylki-Szymańska, A.; Czartoryska, B.; Wegrzyn, A.; Wegrzyn, G. (Jul 2006). “Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses”. European Journal of Human Genetics. 14 (7): 846–52. 
  6. Poorthuis BJ, Wevers RA, Kleijer WJ, et al. (1999). “The frequency of lysosomal storage diseases in The Netherlands”. Hum. Genet. 105 (1–2): 151–6
  7. Sanfilippo, S. J.; Podosin, R.; Langer, L. O., Jr.; Good, R. A. : Mental retardation associated with acid mucopolysacchariduria (heparitin sulfate type). J. Pediat. 63: 837-838, 1963.

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