What Are the Symptoms of Sanfilippo Syndrome

Page reviewed by: Dr. Cara O’Neill, FAAP

Page last updated: May 23, 2022

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Children with Sanfilippo Syndrome appear healthy at birth and typically do not show obvious symptoms of the disease.

However, even early on, many common childhood conditions are consistently early symptoms seen in children with Sanfilippo that are related to the disease. These early symptoms can be easily dismissed and families are often reassured that the child “will grow out of it.”

It is necessary to look at the whole picture of what is going on with your child. If more than one of the following signs or symptoms are noted, it is important to consider checking for Sanfilippo.

Early Symptoms of Sanfilippo:

  • Transient Tachypnea Of Newborn*
    (fast breathing after birth)
  • Coarse Facial Features*
    (frontal bossing/prominent forehead, full lips and nose)
  • Prominent, thick eyebrows*
  • Persistent Hirsutism*
    (execessive body hair)
  • Macrocephaly*
    (large head size)
  • Speech & Developmental Delays+
  • Hearing Loss+
    (typically high-frequency, sensorineural hearing loss)
  • Recurrent Ear/Sinus Infections
  • Chronic Upper Respiratory Congestion
    (persistent nasal congestion/drainage)
  • Challenging Behaviors
    (hyperactivity, impulsivity, poor sense of safety, difficulty cooperating)
  • Features of Autism
    (speech regression, mouthing/oral fixation, loss of interest in social interactions, repetitive speech/behaviors)
  • Sleep Disturbances
    (difficulty going to sleep; frequent nighttime waking, often with disruptive behaviors; difficulty getting back to sleep)
  • Diarrhea/Chronic Loose Stools
  • Umbilical/Inguinal Hernia
  • Enlarged Liver/Spleen

*The most-specific indicators of Sanfilippo syndrome in infants, as reported in Escolar C, Bradshaw J, Byers V, et. al, 2020, Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III. Journal of Inborn Errors of Metabolism & Screening. 2020, Volume 8: e20200002.
+Early neurological features of Sanfilippo.

Facial Features of Sanfilippo

Children with Sanfilippo Syndrome often display some common facial features. These facial features also progress (or coarsen) as the child grows older.

Frontal Bossing | An unusually promiment forehead, sometimes with a with a heavier-than-normal brow ridge.

Prominent, Thick Eyebrows | The eyebrows are typically larger in size than average and have more abundant hair. As the child ages, the eyebrows thicken further and may converge.

Full Lips & Nose | Typically a narrow upper lip and unusually full lower lip. The nose is typically larger than average.

Examples of facial features of children with Sanfilippo compared to their unaffected siblings

The following show the age progression of children with Sanfilippo Syndrome, compared to their unaffected sibling at similiar ages.

Facial features of boy with Sanfilippo, compared to sibling
Facial features of girl with Sanfilippo, compared to sibling
Photo Array Source: Escolar C, Bradshaw J, Byers V, et. al, 2020, Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III. Journal of Inborn Errors of Metabolism & Screening. 2020, Volume 8: e20200002.

Later Features of Sanfilippo:

  • Continued Coarsening of Facial Features
  • Development of features of Autism
  • Progressive Intellectual Disability
  • Brain Atrophy (shrinking of brain tissue from loss of nerve cells)
  • Seizures/Movement Disorders
  • Behavioral problems
  • Hyperactivity
  • Impulsivity
  • Loss of Ambulation
  • Loss of Oral Feeding
    (chewing and swallowing problems)
  • Enlarged Liver/Spleen
  • Hearing Loss
    (typically high-frequency, sensorineural hearing loss)
  • Early Death

Sanfilippo is present at birth, but often goes undetected for years

Signs of Sanfilippo can be present in the newborn period, but often go unnoticed without newborn screening. Most early symptoms of Sanfilippo begin to be recognized between 1 and 6 years of age when the child begins showing signs of developmental delay. and undertake formal assessment.

Because of its rarity, the disease remains largely unfamiliar to most medical practitioners. It is not uncommon that parents search for years to find the cause of their child’s difficulties before a correct diagnosis is made. Sanfilippo can masquerade as ADHD (attention deficit hyperactivity disorder), autism, and intellectual disability. Because of this delay in finding the underlying diagnosis, many families have had other children born in the meantime … only to find out that their younger children are also affected with the disease.

As Sanfilippo progresses, children will typically develop extreme hyperactivity and behavioral problems. Sleep problems become so severe that they may not sleep for days or for only a few hours per night. They gradually lose all the abilities and skills they had acquired, such as speaking, walking, and the ability to eat by mouth.

Figure depicting progressive disability of Sanfilippo Syndrome in child compared to a neurotypical child

What to do if you suspect Sanfilippo

If your child has any of these symptoms or you are concerned they might have Sanfilippo, the next step is to contact your child’s primary care provider and request testing for Sanfilippo. Use the information below to aid your discussion with them.