MPS III has an overall estimated prevalence from 1 in 50,000 to 1 in 250,000 live births. The prevalence of subtypes varies geographically. Type A is the most common globally and is more prevalent in Northern Europe and Eastern Europe. Type B is the most prevalent subtype in Southern Europe. Types C and D are much less common overall, with estimated global incidences of 1:1,500,000 and 1:1,000,000 respectively.

MPS III is caused by mutations in the SGSH, NAGLU, HGSNAY and GNS genes. These genes encode enzymes necessary for the breakdown of heparan sulfate. Mutations can lead to a complete or partial loss of enzyme activity, resulting in the accumulation of heparan sulfate in cellular compartments called lysosomes and subsequent cellular dysfunction. The disorder is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition (see RareShare Guide on Genetic Inheritance).

Symptoms of MPS III generally appear between ages 2 and 6 and may vary in severity and progress over time, including:

• Developmental Delays: Slow cognitive and physical development compared to peers.

• Cognitive Impairments: Progressive intellectual disability and learning difficulties.

• Behavioral Issues: Hyperactivity, aggression and sleep disturbances.

• Motor Skill Regression: Loss of previously acquired skills as the disease progresses.

• Physical Features: Coarse facial features, such as a broad nose, thick lips, thick hair and eyebrows.

• Joint Stiffness: Progressive stiffness and pain leading to mobility issues.

• Organomegaly: Enlargement of the liver and spleen.

• Hearing Loss and Vision Problems: Progressive impairment due to structural changes.

Diagnosis typically involves a combination of clinical evaluation and laboratory tests:

• Clinical assessment of symptoms, physical features and family history.

• Enzyme Activity Test: Measurement of alpha-N-acetylglucosaminidase activity in blood, skin fibroblasts or other tissues. A significant reduction or absence confirms the deficiency.

• Urine Analysis: Elevated levels of heparan sulfate in urine can be indicative, though not specific to MPS IIIB.

• Genetic Testing: Identifying mutations in the NAGLU gene provides definitive confirmation of the diagnosis.

• Imaging Studies: X-rays or MRIs can assess skeletal abnormalities, organ enlargement and neurological involvement.

• Prenatal Diagnosis: Enzyme analysis or genetic testing of fetal cells obtained through amniocentesis or chorionic villus sampling for at-risk pregnancies.

Currently, there is no cure for MPS III. Treatment focuses on managing symptoms and improving the quality of life:

• Supportive Care: Physical, occupational, and speech therapy to improve functionality.

• Behavioral Therapy: Address cognitive and behavioral challenges.

• Symptomatic Treatment: Medications for joint pain, sleep issues and infections.

• Nutritional Support: Ensuring a balanced diet to support growth and health.

• Experimental Therapies: Investigational options like gene therapy, enzyme replacement and substrate reduction therapy are in research phases.

The disease is progressive, and symptoms typically worsen over time. Affected individuals often experience a decline in cognitive and physical abilities, with many requiring significant support for daily living. Life expectancy may be reduced, with many individuals living into their teenage years or early adulthood. Supportive care can help improve quality of life, but the lack of a curative treatment underscores the importance of ongoing research for effective therapies.

1. Andrade, F., Aldámiz-Echevarría, L., Llarena, M. & Couce, M. L. (2015). “Sanfilippo syndrome: Overall review.” Pediatrics International, 57(3), 331-338.

2. Fedele, A. O. (2015). Sanfilippo syndrome: causes, consequences, and treatments. The Application of Clinical Genetics, 8, 269-281.

3. Orphanet: Mucopolysaccharidosis type 3. (n.d.). Mucopolysaccharidosis Type 3.

4. Mucopolysaccharidosis Type III. (n.d.). NORD (National Organization for Rare Disorders). Mucopolysaccharidosis Type III | Sanfilippo Syndrome | NORD.