What are Mucopolysaccharidoses?

Mucopolysaccharidoses (MPS) are a group of Lysosomal disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). GAGs are long chains of sugar molecules used in the building of connective tissues in the body.

Because individuals with MPS have a deficiency in one of the enzymes required to break down these sugar chains, GAGs accumulate in cells, blood, and connective tissues, leading to progressive cellular damage that affects appearance, physical abilities, organ and system functioning, and, in most cases, mental development.

There are several types of MPS, each involving a different enzyme deficiency and having a range of symptoms, severity, and age of onset:

MPS I (Hurler, Hurler-Scheie, Scheie syndromes): It is characterized by a deficiency of the enzyme alpha-L-iduronidase. The severity of symptoms varies widely among individuals.

MPS II (Hunter syndrome): This type affects males almost exclusively and results from a deficiency of the enzyme iduronate-2-sulfatase.

MPS III (Sanfilippo syndrome): There are four subtypes (A, B, C, and D), each caused by the deficiency of a different enzyme. This type mainly affects the central nervous system.

MPS IV (Morquio syndrome): Like MPS III, there are two subtypes, A and B, involving different enzyme deficiencies. This type primarily affects the skeleton.

MPS VI (Maroteaux-Lamy syndrome): It is associated with a deficiency of the enzyme arylsulfatase B and has symptoms similar to MPS I, but it does not affect intelligence.

MPS VII (Sly syndrome): Caused by a deficiency of the enzyme beta-glucuronidase, it has a broad spectrum of symptoms that vary in severity.

MPS IX (Natowicz syndrome): It is a very rare form of MPS caused by a deficiency of the enzyme hyaluronidase.

How to diagnose?
MPS are diagnosed through a combination of clinical evaluation (physical exam, skeletal X-rays, echocardiogram), biochemical tests (urine and serum for measurement of GAGs), specific enzyme assays on blood or white cells and less often skin fibroblasts are performed to determine which enzyme is deficient and genetic testing to confirm the diagnosis and identify the mutation associated with a specific type of MPS. MPS I and II are also part of the newborn screening test, depending on the state, in the United States.

Symptoms include distinctive features such as coarse face, skeletal abnormalities, joint stiffness, and organomegaly (enlargement of organs like the liver and spleen). There is variable cognitive involvement depending on the specific type of MPS. MPSIII exclusively affects the Central Nervous System (CNS) with minimal systemic symptoms.

What is the treatment?
Currently, for certain types of MPS, patients have three options, enzyme replacement therapy, bone marrow, and hematopoietic stem cell transplant.

The treatment strategies for Mucopolysaccharidoses (MPS) vary depending on the type and severity of the disorder. Here’s a general overview of treatment options for each type:

MPS I (Hurler, Hurler-Scheie, Scheie syndromes):
Enzyme Replacement Therapy (ERT) with laronidase (Aldurazyme®) is commonly used.
Hematopoietic Stem Cell Transplantation (HSCT) may be considered, especially in severe cases (Hurler syndrome).

MPS II (Hunter syndrome):
ERT with idursulfase (Elaprase®) is the primary treatment.
HSCT can be considered in some cases, although its effectiveness in MPS II is less clear than in MPS I.

MPS III (Sanfilippo syndrome):
There is no ERT or HSCT currently approved for MPS III because these treatments have not been shown to cross the blood-brain barrier effectively.
Symptomatic treatments to manage behavior problems, sleep disturbances, and other neurological symptoms are the mainstay.

MPS IV (Morquio syndrome):
For MPS IV A, ERT with elosulfase alfa (Vimizim®) is used to treat systemic manifestations.
No specific enzyme therapy is available for MPS IV B; treatment is supportive.

MPS VI (Maroteaux-Lamy syndrome):
ERT with galsulfase (Naglazyme®) is used to manage the symptoms.

MPS VII (Sly syndrome):
ERT with vestronidase alfa (MEPSEVII™) has been approved for the treatment of MPS VII.
HSCT may be considered in some instances.

MPS IX (Natowicz syndrome):
Due to its rarity, no specific treatments for MPS IX are currently available. Management is symptomatic and supportive.

Supportive and Symptomatic Care Across All Types:
  • Orthopedic Care: Surgery for bone and joint issues.
  • Cardiac Care: Monitoring and managing heart disease.
  • Respiratory Support: Treatment for airway obstruction and sleep apnea.
  • Physical and Occupational Therapy: To improve mobility and daily living skills.
  • Neurological Support: Management of seizures and hydrocephalus if present.
  • Ophthalmologic Care: Addressing vision problems.
  • Audiological Care: Managing hearing loss.
  • Gastrointestinal Support: Dietary management for gastrointestinal symptoms.

Clinical Trials and Experimental Therapies:
Research is ongoing for gene therapy and other novel treatments. Participation in clinical trials may be an option for some patients.

Genetic Counseling and Family Support:
Important for discussing inheritance patterns, family planning, and support networks.

The treatment of MPS is complex and requires a multidisciplinary approach tailored to the needs of each individual patient. It's essential to manage not only the physical symptoms of the disease but also to provide psychological and social support to patients and their families.

1,000 to 100,000Estimated Cases Worldwide

MPS Types

MPS I H/S (Hurler/Scheie syndrome)

MPS II-(Hunter syndrome)

MPS III A, B, C, and D (Sanfillipo syndrome)

MPS IV (Morquio syndrome A and B)

MPS VI (Maroteaux-Lamy syndrome)

MPS IX (Natowicz syndrome/Hyaluronidase deficiency)


Wide Range by Type:

Short stature

Irregular breathing

Enlarged spleen and heart

Joint issues

*See details for each type

  • Enzyme Replacement Therapy (ERT)
  • Haematopoietic Stem Cell transplantation (HSCT)                            (Gene therapy, brain penetrant ERT)
* Other treatments under development