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Mucopolysaccharidosis Vi

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Description: Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome) is a rare, inherited metabolic disorder caused by the deficiency of arylsulfatase B, leading to the accumulation of glycosaminoglycans in the body's tissues.
Type: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive genetic disorder.
Signs And Symptoms: Unlike other MPS diseases, children with Maroteaux–Lamy syndrome usually have normal intelligence. They share many of the physical symptoms found in Hurler syndrome. Maroteaux–Lamy syndrome has a variable spectrum of severe symptoms. Neurological complications include clouded corneas, deafness, thickening of the dura (the membrane that surrounds and protects the brain and spinal cord), and pain caused by compressed or traumatized nerves and nerve roots.At birth, people with Maroteaux–Lamy syndrome typically do not display any signs or symptoms. Signs are revealed early in the affected child's life, with one of the first symptoms often being a significantly prolonged age of learning how to walk. Growth begins normally, but children usually stop growing by age 8. By age 10, children often develop a shortened trunk, crouched stance, and restricted joint movement. In more severe cases, children also develop a protruding abdomen and forward-curving spine. Skeletal changes, particularly in the pelvis, are progressive and limit movement. Many children also have umbilical hernia or inguinal hernias. Nearly all children have some form of heart disease, usually involving the heart valves. Individuals with MPS VI may also experience macrocephaly, hydrocephalus, distinctive coarse facial features, macroglossia, dysostosis multiplex, and hepatosplenomegaly. In children with MPS VI, carpal tunnel syndrome commonly develops.
Prognosis: The life expectancy of individuals with MPS VI varies depending on the severity of symptoms. Without treatment, some individuals may survive through late childhood or early adolescence. People with milder forms of the disorder usually live into adulthood, although they may have reduced life expectancy. Heart disease and airway obstruction are major causes of death in people with Maroteaux–Lamy syndrome.
Onset: Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, typically has an onset in early childhood.
Prevalence: Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a rare genetic disorder. Its prevalence is estimated to be approximately 1 in 200,000 to 300,000 live births.
Epidemiology: Males and females are affected equally. Studies have shown a birth prevalence between 1 in 43,261 and 1 in 1,505,160 live births. These numbers are likely an underestimate of the true number of cases, because newborn screening for MPS-VI is not widely available. Although studies have not revealed an ethnic predisposition, certain groups with a high degree of consanguinity have a higher prevalence of MPS-VI. For example, one study of a population of Turkish immigrants in Germany revealed that this group had a rate of 1 in 43,261; this was approximately ten times higher than the rate of MPS-VI in non-Turkish Germans. In different populations worldwide, MPS-VI made up between 2 and 18.5% of all MPS disorders.
Intractability: Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, is considered an intractable disease. This means it currently has no cure and presents significant challenges in management. Treatments such as enzyme replacement therapy (ERT) can help manage symptoms and improve quality of life, but they do not cure the underlying genetic disorder.
Disease Severity: Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, can vary in severity. The disease's severity typically depends on the specific genetic mutation and the resulting level of enzyme activity. It ranges from mild to severe forms. Severe cases can present in early childhood with rapid progression, leading to significant physical abnormalities, organ involvement, and reduced life expectancy. Milder cases may present later in life with more moderate symptoms and slower progression.
Healthcare Professionals: Disease Ontology ID - DOID:12800
Pathophysiology: Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder caused by a deficiency in the enzyme arylsulfatase B (ASB). This enzyme deficiency leads to impaired degradation of glycosaminoglycans (GAGs) such as dermatan sulfate. The accumulated GAGs within lysosomes cause cellular engorgement and disrupt normal cellular functions, leading to progressive damage in multiple organ systems including the skeletal system, eyes, heart, and respiratory system. The severity of clinical manifestations can vary widely among affected individuals.
Carrier Status: Carrier status for Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, is autosomal recessive. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the disease.
Mechanism: Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder. The primary mechanism involves a deficiency of the enzyme arylsulfatase B. This enzyme is critical for the degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate.

When arylsulfatase B is deficient or malfunctioning due to mutations in the ARSB gene, dermatan sulfate accumulates in lysosomes. This accumulation disrupts cellular function and leads to the wide range of clinical manifestations observed in MPS VI, such as skeletal abnormalities, impaired growth, and organ dysfunction.

In summary, the molecular mechanism of MPS VI includes:
1. **Gene Mutation**: Mutations in the ARSB gene.
2. **Enzyme Deficiency**: Reduction or absence of arylsulfatase B activity.
3. **Substrate Accumulation**: Build-up of dermatan sulfate in lysosomes.
4. **Pathological Consequence**: Disruption of normal cellular functions leading to the disease phenotype.
Treatment: The treatment of Maroteaux–Lamy syndrome is symptomatic and individually tailored. A variety of specialists may be needed. In 2005, the FDA approved the orphan drug galsulfase (Naglazyme) for the treatment of Maroteaux–Lamy syndrome. Galsulfase is an enzyme replacement therapy (ERT) in which the missing ASRB enzyme is replaced with a recombinant version.In addition to ERT, various procedures can alleviate the symptoms of MPS-VI. Surgery may be necessary to treat abnormalities such as carpal tunnel syndrome, skeletal malformations, spinal cord compression, hip degeneration, and hernias. Some patients may need heart valve replacement. It may be necessary to remove the tonsils and/or adenoids. Severe tracheomalacia may require surgery. Physical therapy and exercise may improve joint stiffness.Hydrocephalus may be treated by the insertion of a shunt to drain excess cerebrospinal fluid. A corneal transplantation can be performed for individuals with severe corneal clouding. A myringotomy, in which a small incision is made in the eardrum, may be helpful for patients with fluid accumulation in the ears. Hearing aids may be useful, and speech therapy may help children with hearing loss communicate more effectively.Certain medications can be used to treat heart abnormalities, asthma-like episodes, and chronic infections associated with MPS-VI. Anti-inflammatory medications may be of benefit. Respiratory insufficiency may require treatment with supplemental oxygen. Aggressive management of airway secretions is necessary as well. Sleep apnea may be treated with a CPAP or BPAP device.
Compassionate Use Treatment: For Mucopolysaccharidosis VI (MPS VI), compassionate use treatments and experimental therapies may be considered for patients who do not respond adequately to standard treatments or who have advanced disease stages.

1. **Compassionate Use:**
- **Vestronidase Alfa:** Though mainly approved for MPS VII, it may be considered under compassionate use for MPS VI due to its role in addressing similar enzyme deficiencies.
- **Stem Cell Transplantation:** Though risky, stem cell transplantation may be explored under compassionate grounds for severe cases to provide potential long-term benefits.

2. **Off-label or Experimental Treatments:**
- **Gene Therapy:** Though still largely experimental, gene therapy aims to introduce functional genes to correct the underlying deficiency of arylsulfatase B.
- **Substrate Reduction Therapy (SRT):** This approach aims to reduce the production of glycosaminoglycans (GAGs) to slow disease progression and is under investigation.
- **Pharmacological Chaperones:** Small molecules that stabilize the faulty enzyme could be explored as a means to enhance its activity.
- **Intrathecal Enzyme Replacement Therapy (ERT):** Delivering enzyme replacement therapy directly into the cerebrospinal fluid to address central nervous system symptoms is under clinical investigation.

Patients interested in these options should consult specialized medical centers and clinical trials databases to explore availability and eligibility.
Lifestyle Recommendations: For individuals with Mucopolysaccharidosis type VI (MPS VI), managing lifestyle can be important to improve quality of life and overall health. Here are some general recommendations:

1. **Regular Physical Activity**: Engage in physical therapy and low-impact exercises to help maintain joint mobility and muscle strength. Activities like swimming can be beneficial due to reduced joint stress.

2. **Healthy Diet**: Maintain a balanced diet to support overall health and prevent obesity, which can place additional stress on already compromised joints.

3. **Monitor Respiratory Health**: Regular check-ups with a pulmonologist can help manage and monitor any respiratory issues, which are common in MPS VI patients.

4. **Regular Medical Follow-ups**: Frequent consultations with a multidisciplinary team of specialists, including geneticists, cardiologists, orthopedic surgeons, and neurologists, can help in managing symptoms and complications.

5. **Pain Management**: Work with healthcare providers to manage pain, which is often a part of MPS VI, through medication, physical therapy, or other interventions.

6. **Adaptive Equipment**: Utilize assistive devices such as braces, walkers, or wheelchairs as needed to promote independence and safety in daily activities.

7. **Educational Support**: Engage with educational institutions to ensure that any learning difficulties or physical limitations are adequately supported, ensuring that children with MPS VI have access to custom educational plans.

8. **Support Groups and Counseling**: Emotional and psychological support through counseling and support groups can be beneficial for both patients and their families in coping with the challenges of MPS VI.

9. **Hydrotherapy**: Participating in hydrotherapy sessions can help reduce pain and improve mobility in a low-resistance environment.

10. **Cardiac Health**: Regular cardiovascular check-ups are critical, as MPS VI can affect heart function over time.

Adhering to these lifestyle recommendations can help manage the symptoms of MPS VI and enhance overall well-being.
Medication: For Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, enzyme replacement therapy (ERT) with the medication galsulfase (brand name Naglazyme) is commonly used. Galsulfase works by replacing the deficient enzyme, N-acetylgalactosamine-4-sulfatase, to help break down glycosaminoglycans (GAGs), which accumulate in the cells of individuals with this condition. This treatment can help manage symptoms and improve quality of life.
Repurposable Drugs: Currently, there are no widely recognized repurposable drugs specifically for Mucopolysaccharidosis VI (MPS VI). MPS VI, also known as Maroteaux-Lamy syndrome, is typically treated with enzyme replacement therapy using galsulfase (Naglazyme). For accurate and updated information on potential treatments, consult a medical professional or authoritative sources in medical literature.
Metabolites: Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder. The primary metabolites that accumulate in MPS VI are dermatan sulfate. Due to the deficiency of the enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B), dermatan sulfate is not properly broken down and thus accumulates in various tissues, leading to the symptoms associated with the disorder.
Nutraceuticals: As of now, no specific nutraceuticals are proven to treat or cure Mucopolysaccharidosis VI (MPS VI). MPS VI, also known as Maroteaux-Lamy syndrome, is a rare lysosomal storage disorder caused by the deficiency of the enzyme arylsulfatase B. Management typically involves enzyme replacement therapy (ERT) with galsulfase (Naglazyme) and other supportive treatments to address symptoms and improve quality of life. Nutraceuticals could potentially contribute to overall health, but their efficacy for MPS VI specifically is not established. Always consult healthcare providers for treatment guidance tailored to individual needs.
Peptides: Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder caused by a deficiency in the enzyme arylsulfatase B (ARSB). This deficiency leads to the accumulation of glycosaminoglycans (GAGs) in various tissues.

**Peptides in MPS VI:**
The primary enzyme, ARSB, involved in breaking down certain complex sugars (dermatan sulfate) is a polypeptide. Enzyme replacement therapy (ERT) using recombinant human ARSB, such as galsulfase, is used to manage symptoms and improve outcomes in MPS VI patients.

**Nanotechnology in MPS VI:**
Nanotechnology approaches, such as nanoparticle-based drug delivery systems, are being researched to improve the efficacy and targeting of therapies for MPS VI. These systems can potentially enhance the delivery of therapeutic molecules across biological barriers, reducing side effects and improving treatment outcomes.