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What is Sanfilippo Syndrome

What is Sanfilippo Syndrome?

Sanfilippo syndrome is caused by a defect in a single gene. It is an inherited disease of metabolism; the body cannot properly break down long chains of sugar molecules called mucopolysaccharides or glycosaminoglycans (aka GAGs). Sanfilippo syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS III.  Sanfilippo syndrome occurs when the enzymes the body needs to break down the Heparan Sulfate (HS) are absent or are defective. When HS is not broken down, the body does not release it. Instead, it is stored inside the lysosomes of every cell in the body.

This is why Sanfilippo syndrome is classified as a Lysosomal Storage Disease (LSD). As the GAGs accumulate, they damage the cells they are stored in. This leads to the progressive degeneration of the central nervous system.


To date, there are four types of Sanfilippo syndrome. They are distinguished by the enzyme that is affected.  Combined, it is estimated that the four types of Sanfilippo presents in approximately 1 in 70,000 births. The incidence rate of Sanfilippo’s subtype is not well documented, more epidemiology studies need to be conducted. Sanfilippo type A and B are thought to have a more severe phenotype then subtypes C and D. Due to the heterogeneity of Sanfilippo syndrome it is difficult to predict the rate of decline or severity for any given subtype.

  • Sanfilippo Type A: heparan N-sulfatase. Estimated incident rate is 1 in 100,000 live births.

  • Sanfilippo Type B: alpha-N-acetylglucosaminidase. Estimated incident rate is 1 in 200,000 live births.

  • Sanfilippo Type C: acetyl-CoAlpha-glucosaminide acetyltransferase. Estimated incident rate is 1 in 1,400,000.

  • Sanfilippo Type D: N-acetylglucosamine 6-sulfatase. Estimated incident rate is 1 in 1,100,000.

Stages of Sanfilippo Syndrome

Sanfilippo is an insidious disease that often goes undetected for years. Most children are born with no significant signs suggesting that something might be wrong. It’s not until the preschool years that children start to show delays; even then, the disease is often misdiagnosed.


Sanfilippo is progressive and can be broken down into stages.  Please take note, as horrific as these stages sound, children affected by Sanfilippo syndrome are gregarious, loving, and happy children.

First Stage

The early hallmarks of Sanfilippo syndrome are so benign that they may go undetected or are not scrutinized by pediatricians for years.  Affected children are prone to frequent sinus infections, ear infections, and chronic diarrhea. Minor bone deformities may include a raised sternum, oar shaped ribs and frontal bossing. Hepatosplenomegaly, an enlarged liver and spleen are common.

Second Stage

The affected child will present with hyperactivity and speech delays, they are often diagnosed with ADHD, Autism and or oppositional defiance disorder.  They’re restless, suffer from sleeplessness and exhibit difficult behavior. Irrational fears are common, but most children are fearless, with little regard to dangerous situations. Many children are compelled to chew on things- doctors may diagnose this as a sensory processing disorder.  Some children exhibit inconsolable behaviors such as screaming for no apparent reason, hysterical laughing fits or crying and writhing as if in pain.  Some children have seizures others have visual and hearing problems.  The child’s facial features will begin to coarsen, coarse facial features depict a rounded appearance of the brow, nose, lips, mouth and chin. The skin appears thickened or heavy.  An affected child has coarse hair as well, turning from a smooth texture to a thick and kinky texture. Over time, speech loss occurs, and communication skills decline along with cognitive regression and loss of motor skills.

Third Stage

The disease will take its ultimate toll. The child will lose the ability to walk, talk and eat on their own. Death may occur in the first decade of life. More common, however, are children that live into their teens. Children with attenuated forms of Sanfilippo have been reported to live to the 3rd or 4th decade, but with a poor quality of life.  Children often succumb to pneumonia or other types of infections.

Physical Features of Sanfilippo Syndrome Children

Coarse Facial Features

Coarse facial features are a medical term used to describe an absence of fine, sharp appearance of the brows, nose, lips, mouth, ears, and chin.  In a Sanfilippo child, these features are rounded in appearance due to heavy thick skin.

Hepatosplenomegaly and Umbilical Hernia

Sanfilippo children usually present with hepatomegaly; enlarged liver and or hepatosplenomegaly; enlarged liver and spleen. Usually present at birth but not considered to be of any significance. As the child ages the visible appearance of hepatomegaly lessons.

Hair Growth and Texture Change

Synophrys, the medical term for monobrow is common among children with Sanfilippo syndrome. As well as hirsutism (mustache) in boys and girls.

Frontal Bossing

Of all the MPS’s Sanfilippo syndrome has the mildest form of dysostosis multiplex. The most prominent bone deformity of Sanfilippo children is their skull deformity. Frontal bossing is a medical term used to describe a prominent protruding forehead.  This feature is most likely the most common feature of Sanfilippo which is also visible at birth. Yet, it is almost always ignored at birth and disregarded by the child’s pediatrician. 


Other common bone deformities in Sanfilippo syndrome may include abnormally shaped vertebrae, spatulate or flared ribs, short stature and hip dysplasia.

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