Conditions · Metabolism (biochemistry)
Sanfilippo syndrome (mucopolysaccharidosis type III) !
Sanfilippo syndrome is the most common mucopolysaccharidosis. Heparan sulfate builds up mainly in the brain, causing behaviour problems and loss of skills.
Updated 2026-11-01
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In biochemistry
What it is
A group of four autosomal recessive lysosomal diseases (MPS IIIA–D), each missing one enzyme of heparan sulfate breakdown; the central nervous system bears the brunt while body features stay mild.
Who gets it
The commonest mucopolysaccharidosis, with about 1 in 70 000 newborns for the four types together; IIIA and IIIB are much more frequent than IIIC and IIID. No Colombian figure appears in the sources consulted.
Causes
- MPS IIIA: SGSH (heparan N-sulfatase)
- MPS IIIB: NAGLU (α-N-acetylglucosaminidase)
- MPS IIIC: HGSNAT (acetyl-CoA:α-glucosaminide N-acetyltransferase)
- MPS IIID: GNS (N-acetylglucosamine 6-sulfatase)
Risk factors
- Both parents carriers
- Consanguinity
Pathophysiology
Heparan sulfate is broken down from its end one step at a time; each of the four enzymes handles one step. Losing any of them stops the chain, and partly degraded heparan sulfate fills the lysosomes, especially in neurons, where it disturbs other lysosomal enzymes and secondarily stores gangliosides. Dermatan sulfate is spared, so skeletal and visceral signs are milder than in Hurler or Hunter syndromes.
Classification
- MPS IIIA (usually earliest onset and fastest course)
- MPS IIIB
- MPS IIIC
- MPS IIID
Symptoms and signs
- Speech and developmental delay in early childhood
- Hyperactivity, restlessness, aggression, fearlessness; autism-like features
- Putting objects in the mouth (hyperorality)
- Severe sleep disturbance
- Regression and dementia; later seizures and loss of walking
- Mildly coarse features, large head, thick hair and eyebrows
- Mild hepatosplenomegaly, umbilical or inguinal hernia, chronic diarrhoea
- Recurrent ear infections and hearing loss
Diagnosis
- Clinical
- A child with language delay, marked hyperactivity and sleep problems, mild coarse features and later regression; it is often first labelled as autism or ADHD.
- Tests
- Urine glycosaminoglycans with heparan sulfate only (screening tests can be falsely normal); enzyme activity of the four enzymes in leukocytes or fibroblasts; gene testing (SGSH, NAGLU, HGSNAT, GNS); audiometry.
- Imaging
- Brain MRI with cortical atrophy and white-matter changes; skeletal X-rays may show mild dysostosis multiplex.
Treatment
- Medical
- Symptomatic care for sleep, behaviour and seizures; brain-directed enzyme and gene therapies are in trials or under regulatory review, and availability varies by country.
- Surgical
- Adenotonsillectomy, ear tubes and hernia repair when needed.
- Rehabilitation
- Speech, occupational and physical therapy adapted to each stage.
- Follow-up
- Follow-up of hearing, vision, heart and nutrition, with palliative care in late stages.
Complications
- Dementia and loss of mobility
- Seizures
- Aspiration pneumonia
- Hearing loss
- Cardiomyopathy or valve disease (less common)
Prognosis
Most people live into adolescence or early to mid-adulthood; type IIIA tends to progress fastest.
Prevention
- Genetic counselling and carrier testing in families
- Prenatal or preimplantation diagnosis when the variants are known
Test yourself
Think of the answer, then tap the question to see it.
Which glycosaminoglycan accumulates in Sanfilippo syndrome?
Heparan sulfate only; dermatan sulfate is spared, which is why the body features are milder than in Hurler syndrome.
Which organ system dominates the picture in MPS III?
The central nervous system: behaviour problems, sleep disturbance, regression and dementia, with mild somatic signs.
How many enzyme defects cause MPS III, and which type is most severe?
Four (types A–D: SGSH, NAGLU, HGSNAT, GNS); type IIIA usually starts earliest and progresses fastest.
Why can Sanfilippo syndrome be missed at first?
Early signs look like autism or ADHD, physical features are subtle, and urine GAG screening can be falsely normal.
Related conditions
- Morquio syndrome (mucopolysaccharidosis type IV)
- Hurler syndrome (mucopolysaccharidosis type I)
- Hunter syndrome (mucopolysaccharidosis type II)
- Epilepsy and seizures
- Umbilical hernia
- Inguinal hernia
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Mucopolysaccharidosis type III: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); SGSH gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); NAGLU gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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