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Mucopolysaccharidosis

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Description: Mucopolysaccharidosis is a group of inherited lysosomal storage disorders characterized by the body's inability to break down glycosaminoglycans, leading to progressive physical and neurological deterioration.
Type: Mucopolysaccharidosis (MPS) refers to a group of metabolic disorders. Types and their genetic transmissions are as follows:

1. **MPS I (Hurler, Scheie, and Hurler-Scheie syndromes)**: Autosomal recessive.
2. **MPS II (Hunter syndrome)**: X-linked recessive.
3. **MPS III (Sanfilippo syndrome, types A, B, C, and D)**: Autosomal recessive.
4. **MPS IV (Morquio syndrome, types A and B)**: Autosomal recessive.
5. **MPS VI (Maroteaux-Lamy syndrome)**: Autosomal recessive.
6. **MPS VII (Sly syndrome)**: Autosomal recessive.
7. **MPS IX**: Autosomal recessive.

Each type is caused by a deficiency in specific enzymes needed to break down glycosaminoglycans.
Signs And Symptoms: The mucopolysaccharidoses share many clinical features but have varying degrees of severity. These features may not be apparent at birth but progress as storage of GAGs affects bone, skeletal structure, connective tissues, and organs. Neurological complications may include damage to neurons (which send and receive signals throughout the body) as well as pain and impaired motor function. This results from compression of nerves or nerve roots in the spinal cord or in the peripheral nervous system, the part of the nervous system that connects the brain and spinal cord to sensory organs such as the eyes and to other organs, muscles, and tissues throughout the body.
Depending on the mucopolysaccharidosis subtype, affected individuals may have normal intellect or have cognitive impairments, may experience developmental delay, or may have severe behavioral problems. Many individuals have hearing loss, either conductive (in which pressure behind the eardrum causes fluid from the lining of the middle ear to build up and eventually congeal), neurosensory (in which tiny hair cells in the inner ear are damaged), or both. Communicating hydrocephalus—in which the normal reabsorption of cerebrospinal fluid is blocked and causes increased pressure inside the head—is common in some of the mucopolysaccharidoses. Surgically inserting a shunt into the brain can drain fluid. The eye's cornea often becomes cloudy from intracellular storage, and glaucoma and degeneration of the retina also may affect the patient's vision.
Physical symptoms generally include coarse or rough facial features (including a flat nasal bridge, thick lips, and enlarged mouth and tongue), short stature with disproportionately short trunk (dwarfism), dysplasia (abnormal bone size and/or shape) and other skeletal irregularities, thickened skin, enlarged organs such as liver (hepatomegaly) or spleen (splenomegaly), hernias, and excessive body hair growth. Short and often claw-like hands, progressive joint stiffness, and carpal tunnel syndrome can restrict hand mobility and function. Recurring respiratory infections are common, as are obstructive airway disease and obstructive sleep apnea. Many affected individuals also have heart disease, often involving enlarged or diseased heart valves.
Another lysosomal storage disease often confused with the mucopolysaccharidoses is mucolipidosis. In this disorder, excessive amounts of fatty materials known as lipids (another principal component of living cells) are stored, in addition to sugars. Persons with mucolipidosis may share some of the clinical features associated with the mucopolysaccharidoses (certain facial features, bony structure abnormalities, and damage to the brain), and increased amounts of the enzymes needed to break down the lipids are found in the blood.
Prognosis: Mucopolysaccharidosis (MPS) prognosis varies depending on the specific type and severity of the disease. MPS encompasses several inherited disorders characterized by the accumulation of glycosaminoglycans due to enzyme deficiencies. Generally:

- **MPS I (Hurler syndrome):** Severe form can lead to progressive neurodegeneration, physical deformities, and potentially a shortened lifespan, often into the second decade of life. Milder forms (Scheie syndrome) may have near-normal lifespans with significant morbidities.

- **MPS II (Hunter syndrome):** Lifespan and quality of life can be similarly affected, with severe forms leading to neurological decline and shorter lifespans, whereas milder forms may lead to longer lifespans but with significant physical issues.

- **MPS III (Sanfilippo syndrome):** Typically presents with severe neurological impacts and behavioral problems, often leading to a shortened lifespan (second decade of life).

- **MPS IV (Morquio syndrome):** Life expectancy can vary widely but often includes mobility issues and respiratory problems, sometimes leading to a shorter lifespan but not universally.

- **MPS VI (Maroteaux-Lamy syndrome):** Generally does not affect cognitive abilities but leads to physical deformities and sometimes a shorter lifespan due to complications like heart disease.

- **MPS VII (Sly syndrome):** Rare and can range from severe forms, which affect multiple organs and can lead to a shortened lifespan, to milder forms with longer life expectancies.

Early diagnosis and treatment, including enzyme replacement therapies, can significantly improve outcomes in some forms of MPS. However, the progressive nature of these disorders means that close medical management is essential.
Onset: Mucopolysaccharidosis (MPS) typically has an onset in early childhood. The specific age at onset can vary depending on the type of MPS and the severity of the condition. Symptoms usually appear in the first few years of life, often between ages 1 and 3.
Prevalence: Mucopolysaccharidosis (MPS) refers to a group of rare, inherited metabolic disorders. The prevalence varies by type, but collectively, MPS disorders occur in approximately 1 in 25,000 to 1 in 100,000 live births, depending on the specific subtype and population.
Epidemiology: Mucopolysaccharidosis (MPS) refers to a group of inherited metabolic disorders characterized by the body's inability to break down glycosaminoglycans (GAGs) due to deficiencies in specific lysosomal enzymes. The epidemiology for MPS varies among the different subtypes (e.g., MPS I, II, III, IV, VI, VII). Overall, the prevalence of MPS is estimated to be around 1 in 25,000 live births. Some specific types, like MPS I (Hurler syndrome), have a prevalence of approximately 1 in 100,000 live births. MPS II (Hunter syndrome) is estimated to occur in about 1 in 100,000 to 150,000 live births, affecting primarily males. The various subtypes can be more common in some populations due to founder effects and genetic drift.

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Intractability: Mucopolysaccharidosis (MPS) is generally considered an intractable disease. It is a group of inherited metabolic disorders caused by the inability to break down glycosaminoglycans due to enzyme deficiencies. The disease is progressive and treatments can help manage symptoms and improve quality of life, but there is currently no cure.
Disease Severity: Mucopolysaccharidosis (MPS) varies in severity depending on the specific type and individual case. It is a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down glycosaminoglycans (GAGs). The severity can range from mild to severe, profoundly affecting an individual's physical and cognitive functions.
Healthcare Professionals: Disease Ontology ID - DOID:12798
Pathophysiology: Mucopolysaccharidosis (MPS) is a group of inherited metabolic disorders caused by the deficiency of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Due to the enzyme deficiency, GAGs accumulate within the lysosomes of various tissues, leading to cellular and organ damage. The excessive storage of GAGs results in a variety of symptoms, including growth abnormalities, skeletal deformities, organomegaly, cardiovascular issues, and neurological complications. The exact manifestations and severity of MPS vary depending on the specific enzyme deficiency and subtype of the disorder.
Carrier Status: For mucopolysaccharidosis (MPS):

**Carrier Status:**
MPS is generally inherited in an autosomal recessive manner, meaning that a person needs to inherit two defective copies of the gene (one from each parent) to manifest the disease. Carriers have one defective gene and one normal gene but typically do not show symptoms of the disease. If both parents are carriers, each of their children has a 25% chance of having MPS, a 50% chance of being a carrier, and a 25% chance of inheriting two normal genes.

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Mechanism: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by the deficiency of specific lysosomal enzymes required to degrade glycosaminoglycans (GAGs). The primary mechanism involves the accumulation of partially degraded GAGs within lysosomes, leading to cellular and tissue damage.

Molecular mechanisms involve mutations in genes encoding lysosomal enzymes:
- The mutations result in deficient or dysfunctional enzymes.
- This deficiency impairs the catabolism of GAGs such as dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate.
- Accumulation of these partially degraded GAGs occurs in various tissues, including the skeleton, brain, heart, and other organs.
- The buildup disrupts normal cellular function, leading to the clinical manifestations of MPS, such as skeletal deformities, growth retardation, organomegaly, and neurologic deficits.
Treatment: Currently there is no cure for these disorders. Medical care is directed at treating systemic conditions and improving the person's quality of life. Physical therapy and daily exercise may delay joint problems and improve the ability to move.
Changes to the diet will not prevent disease progression, but limiting milk, sugar, and dairy products has helped some individuals experiencing excessive mucus.
Surgery to remove tonsils and adenoids may improve breathing among affected individuals with obstructive airway disorders and sleep apnea. Sleep studies can assess airway status and the possible need for nighttime oxygen. Some patients may require surgical insertion of an endotrachial tube to aid breathing. Surgery can also correct hernias, help drain excessive cerebrospinal fluid from the brain, and free nerves and nerve roots compressed by skeletal and other abnormalities. Corneal transplants may improve vision among patients with significant corneal clouding.
Enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain. Currently BioMarin Pharmaceutical produces enzyme replacement therapies for MPS type I and VI. Aldurazyme is an enzymatic replacement therapy for alpha-L-iduronidase produced by BioMarin for use in Type I MPS. In May 2005, galsulfase[Naglazyme®], a recombinant enzyme replacement therapy also produced by Biomarin was approved for MPS VI (Marateaux-Lamy syndrome). In July 2006, the United States Food and Drug Administration approved a synthetic version of I2S produced by Shire Pharmaceuticals Group, called Elaprase, as a treatment for MPS type II (Hunter syndrome). Vestronidase alfa (Mepsevii) is a recombinant human lysosomal beta glucuronidase for MPS VII (Sly syndrome) approved in the United States in November 2017 (Ultragenyx).Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) have had limited success in treating the mucopolysaccharidoses. Abnormal physical characteristics, except for those affecting the skeleton and eyes, may be improved, but neurologic outcomes have varied. BMT and UCBT are high-risk procedures and are usually performed only after family members receive extensive evaluation and counseling.
Compassionate Use Treatment: Mucopolysaccharidosis (MPS) encompasses a group of inherited metabolic disorders characterized by the body's inability to break down mucopolysaccharides. Treatments under compassionate use, off-label, or experimental status may include:

1. **Enzyme Replacement Therapy (ERT)**: Some forms are FDA-approved but could be considered compassionate use for other types of MPS not yet approved.

2. **Hematopoietic Stem Cell Transplantation (HSCT)**: This procedure is off-label for certain MPS types. It aims to introduce normal cells to produce the enzyme the patient lacks.

3. **Gene Therapy**: Various gene therapy approaches are under experimental phases and clinical trials, showing promise in potentially curing or significantly alleviating symptoms.

4. **Substrate Reduction Therapy (SRT)**: Experimental SRT aims to reduce the production of glycosaminoglycans (GAGs) that accumulate due to the deficient enzyme.

5. **Chaperone Therapy**: This is an emerging experimental treatment designed to stabilize misfolded enzyme proteins, enhancing their function.

These treatments are tailored based on the specific type of MPS and individual patient circumstances. Current clinical trials and involvement in research studies might provide additional options.
Lifestyle Recommendations: For individuals with mucopolysaccharidosis (MPS), lifestyle recommendations generally focus on managing symptoms and improving quality of life. Here are key considerations:

1. **Regular Medical Follow-ups**: Frequent visits to specialists such as geneticists, orthopedic surgeons, cardiologists, and neurologists are essential for comprehensive care.

2. **Physical Therapy**: Engaging in regular physical therapy can help maintain mobility and manage pain. Customized exercise programs can improve joint function and muscle strength.

3. **Breathing Support**: Respiratory issues are common, so using devices like CPAP (Continuous Positive Airway Pressure) machines during sleep, and monitoring lung function regularly, can be beneficial.

4. **Nutritious Diet**: A well-balanced diet tailored to individual needs can aid in maintaining overall health. Nutritional supplements might be necessary if dietary intake is insufficient.

5. **Pain Management**: Pain management strategies, including medications and alternative therapies like acupuncture or massage, can be effective.

6. **Adapted Living Spaces**: Making adjustments in the living environment, such as installing ramps, handrails, and specialized furniture, can enhance safety and accessibility.

7. **Education Support**: Children with MPS may require special educational services to accommodate learning differences and physical limitations.

8. **Emotional and Psychological Support**: Psychological counseling and support groups can be helpful for both patients and caregivers to cope with the emotional aspects of the condition.

9. **Monitoring for Complications**: Regular monitoring for complications like heart valve issues, vision and hearing problems, and spinal cord compression is crucial.

10. **Occupational Therapy**: Occupational therapy can assist in improving daily living skills and recommending adaptive equipment.

Following these recommendations can assist in managing mucopolysaccharidosis and enhancing the overall quality of life for individuals affected by this condition.
Medication: Mucopolysaccharidosis (MPS) is a group of inherited metabolic disorders characterized by the body's inability to break down glycosaminoglycans. Treatment options include:

1. **Enzyme Replacement Therapy (ERT)**: Specific for different types of MPS, such as laronidase for MPS I, idursulfase for MPS II, and galsulfase for MPS VI.
2. **Hematopoietic Stem Cell Transplantation (HSCT)**: Especially effective in some types like MPS I when performed early.
3. **Supportive Treatments**: Management of symptoms and complications through physical therapy, surgeries for skeletal abnormalities, and medications for pain management.

Emerging therapies and clinical trials are ongoing to improve outcomes and quality of life for patients.
Repurposable Drugs: Repurposable drugs for mucopolysaccharidosis include some that have shown potential in preclinical or preliminary clinical studies. These drugs include:

1. **Genistein**: An isoflavone that may reduce glycosaminoglycan (GAG) accumulation.
2. **Pentosan Polysulfate Sodium**: Has demonstrated some efficacy in reducing GAG levels and improving clinical symptoms.
3. **Gabapentin**: Sometimes used to manage pain in MPS patients.
4. **Ambroxol**: May enhance the activity of residual enzyme in some MPS types.

Note that effectiveness and safety should be thoroughly evaluated in clinical trials before repurposing any drug for mucopolysaccharidosis treatment.
Metabolites: Mucopolysaccharidosis (MPS) is characterized by the accumulation of glycosaminoglycans (GAGs) due to deficiencies in specific lysosomal enzymes. The primary metabolites involved in MPS are various types of GAGs, such as dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate. These compounds accumulate in tissues and organs, leading to the symptoms and complications associated with the disease.
Nutraceuticals: Nutraceuticals are not a standard treatment for mucopolysaccharidosis (MPS), a group of inherited metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down glycosaminoglycans. The primary treatments for MPS include enzyme replacement therapy and hematopoietic stem cell transplantation. Management often also involves supportive therapies like physical therapy, surgeries, and medications for symptom relief. Although some nutraceuticals may be explored in research settings for their potential benefits, they are not currently recognized as a primary or effective treatment for MPS.
Peptides: Mucopolysaccharidosis (MPS) refers to a group of inherited metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down glycosaminoglycans (GAGs). While treatments involving enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) exist, peptide therapies are generally not a primary approach for MPS. Peptide-based treatments have been explored in research for other lysosomal storage disorders but not widely established for MPS. The ongoing research in nanotechnology shows promise for better delivery systems for ERT and gene therapies, potentially improving outcomes for MPS patients.