Mucopolysaccharidosis (MPS)
Mucopolysaccharidoses (MPS) are a group of rare inherited metabolic conditions in which the body cannot properly break down certain complex sugars called glycosaminoglycans (GAGs), previously known as mucopolysaccharides.
Overview
Mucopolysaccharidoses (MPS) are a group of rare inherited metabolic conditions in which the body cannot properly break down certain complex sugars called glycosaminoglycans (GAGs), previously known as mucopolysaccharides. These substances are important components of connective tissue. In MPS, a specific enzyme needed to break down GAGs is missing or does not work properly. As a result, GAGs accumulate within cells, particularly in bones, cartilage, heart valves, airways and, in some types, the brain. MPS disorders are classified into different types (for example MPS I, II, III, IV, VI, VII and IX), depending on which enzyme is affected. Severity varies widely between types and individuals. MPS conditions are types of lysosomal storage disorders.
Causes and Genetics
Each type of MPS is caused by changes (mutations) in a specific gene responsible for producing an enzyme that breaks down glycosaminoglycans (GAGs). When the enzyme does not function correctly, GAGs accumulate progressively within cells and tissues, leading to organ damage over time. Most forms of MPS are inherited in an autosomal recessive pattern, meaning a child must inherit two altered copies of the gene (one from each parent) to develop the condition. MPS II (Hunter syndrome) is inherited in an X-linked pattern and primarily affects males, although females can rarely be affected.
Symptoms and Features
Symptoms depend on the specific type of MPS and the organs involved. Features often become apparent in early childhood and may progressively worsen.
Characteristic Symptoms and Features
- Coarse facial features
- Enlargement of liver and spleen (which can cause abdominal discomfort)
- Joint stiffness and reduced joint mobility
- Reduction in body height
- Hernias
- Frequent ear infections
- Airway narrowing (causing breathing problems)
- Thickened heart valves
- Skeletal abnormalities (sometimes referred to as dysostosis multiplex)
- Progressive bone deformities
Other Associated Symptoms and Features
- Some types are associated with developmental delay and cognitive decline, particularly MPS I (severe form), MPS II (severe form) and MPS III (Sanfilippo syndrome)
- Neurological features may include behavioural difficulties, sleep disturbance, seizures and progressive loss of skills
- Other complications may include hearing loss, vision problems, recurrent respiratory tract infections and heart disease
Severity varies significantly. Some individuals have milder forms with normal intelligence and slower progression.
Treatment
Management usually requires a multidisciplinary team and may include: surgical treatment of hernias or skeletal problems; airway support; cardiac (heart function) monitoring; physiotherapy; hearing aids; vision support; and educational support where needed. Regular monitoring of heart, respiratory function, mobility and development is essential. Patients are usually managed through specialist metabolic centres.
Research and Future Directions
Ongoing research is focused on improving enzyme replacement therapies, developing treatments that can cross the blood-brain barrier to treat neurological involvement, and exploring gene therapy approaches. Studies are also assessing earlier diagnosis through newborn screening, long-term outcomes of treated individuals, and ways to improve quality of life for people living with MPS.