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Sly Syndrome

Disease Details

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Description: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is a rare genetic disorder caused by the deficiency of the enzyme beta-glucuronidase, leading to the accumulation of glycosaminoglycans in the body's cells.

One-sentence description:
Sly syndrome is a rare inherited disorder characterized by the buildup of complex carbohydrates in cells due to a deficient enzyme, resulting in various systemic symptoms and complications.
Type: Sly syndrome, also known as mucopolysaccharidosis type VII (MPS VII), is an inherited lysosomal storage disorder. It is caused by a deficiency of the enzyme beta-glucuronidase. The type of genetic transmission for Sly syndrome is autosomal recessive.
Signs And Symptoms: The most severe cases of Sly syndrome can result in hydrops fetalis, which results in fetal death or death soon after birth. Some people with Sly syndrome may begin to have symptoms in early childhood. Symptoms can include an enlarged head, fluid buildup in the brain, coarse facial features, enlarged tongue, enlarged liver, enlarged spleen, problems with the heart valves, and abdominal hernias. People with Sly syndrome may also have sleep apnea, frequent lung infections, and problems with vision secondary to cloudy corneas. Sly syndrome causes various musculoskeletal abnormalities that worsen with age. These can include short stature, joint deformities, dysostosis multiplex, spinal stenosis, and carpal tunnel syndrome.While some individuals have developmental delay, others may have normal intelligence. However, the accumulation of GAGs in the brain usually leads to the slowing of development from ages 1–3, and then a loss of previously learned skills until death.
Prognosis: The life expectancy of individuals with MPS VII varies depending on the symptoms. Some individuals are stillborn, while some may survive into adulthood.
Onset: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), typically has an onset that can vary widely but is often apparent in early childhood. Signs and symptoms may manifest in infancy or early childhood, though milder cases may not be diagnosed until later in life. The severity and range of symptoms can vary significantly among individuals.
Prevalence: There is limited specific prevalence data for Sly syndrome (mucopolysaccharidosis type VII), but it is considered an extremely rare disorder. Estimates suggest that its prevalence is much lower than 1 in 100,000 live births.
Epidemiology: MPS-VII is one of the rarest forms of MPS. It occurs in less than 1 in 250,000 births. As a family, MPS diseases occur in 1 in 25,000 births, and the larger family of lysosomal storage diseases occur in 1 out of 7,000 to 8,000 births.
Intractability: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is generally considered intractable, meaning it is challenging to manage and treat effectively. While enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) show some potential benefits, they do not cure the disease. The treatments can help manage symptoms and improve quality of life but do not fully halt disease progression. Advances in gene therapy are under research but are not yet widely available as standard treatment.
Disease Severity: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), can vary in severity. It may range from a severe form presenting in infancy with hydrops fetalis, developmental delays, and skeletal abnormalities, to milder forms with symptoms appearing later in childhood or even adulthood. The disease generally involves organ enlargement, respiratory issues, and skeletal dysplasia, often leading to significant morbidity.
Healthcare Professionals: Disease Ontology ID - DOID:12803
Pathophysiology: Sly syndrome, also known as mucopolysaccharidosis type VII (MPS VII), is an autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme beta-glucuronidase. This enzyme is crucial for the breakdown of glycosaminoglycans (GAGs), specifically dermatan sulfate, heparan sulfate, and chondroitin sulfate. The deficiency leads to the accumulation of these GAGs in various tissues and organs, causing a range of clinical manifestations. Accumulated GAGs disrupt normal cellular function, leading to progressive multisystem involvement, which can include skeletal deformities, hepatosplenomegaly, cardiopulmonary issues, and neurological deficits. The severity of symptoms can vary widely among affected individuals.
Carrier Status: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is a genetic disorder caused by mutations in the GUSB gene. Carrier status for Sly syndrome means that an individual has one mutated copy of the GUSB gene but does not exhibit symptoms of the disease. Carriers can pass the mutated gene to their offspring.
Mechanism: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is a lysosomal storage disorder caused by a deficiency of the enzyme beta-glucuronidase. This enzyme is responsible for breaking down glycosaminoglycans (GAGs), which are long chains of sugar molecules found throughout the body, particularly in connective tissues.

**Mechanism:**
In individuals with Sly syndrome, the deficient or non-functional beta-glucuronidase enzyme leads to the accumulation of GAGs within lysosomes, the cellular structures responsible for breaking down many types of biomolecules. This accumulation disrupts the normal function of lysosomes and results in a spectrum of symptoms, including organomegaly (enlarged organs), skeletal abnormalities, and developmental delays.

**Molecular Mechanisms:**
1. **Enzyme Deficiency:** Mutations in the GUSB gene, which encodes the beta-glucuronidase enzyme, result in insufficient enzyme activity. This can be due to missense mutations, nonsense mutations, insertions, deletions, or splice site mutations, impacting the enzyme's synthesis, folding, stability, or activity.

2. **Substrate Accumulation:** The lack of functional beta-glucuronidase enzyme leads to an inability to degrade GAGs like heparan sulfate, dermatan sulfate, and chondroitin sulfate. These undegraded molecules accumulate within lysosomes, leading to cellular and tissue dysfunction.

3. **Cellular Dysfunction:** The intracellular buildup of GAGs causes lysosomal swelling and interferes with cellular processes, triggering secondary storage of other substrates that are not primary targets of beta-glucuronidase. This widespread lysosomal dysfunction affects multiple organ systems.

4. **Inflammation and Fibrosis:** The accumulation of GAGs can provoke inflammatory responses and contribute to fibrosis in various tissues, exacerbating the symptoms and progression of the disease.

Management of Sly syndrome typically involves supportive and symptomatic treatments, with emerging therapies focusing on enzyme replacement, gene therapy, or pharmacological chaperones to address the underlying genetic defect.
Treatment: Vestronidase alfa-vjbk (trade name Mepsevii), an enzyme replacement therapy which is a recombinant form of human β-glucuronidase, is approved by U.S. Food and Drug Administration for the treatment of Sly syndrome. Hematopoietic stem cell transplant (HSCT) has been used to treat other types of MPS diseases, but this is not yet available for MPS-VII. Animal experiments suggest that HSCT may be an effective treatment for MPS-VII in humans.
Compassionate Use Treatment: Sly syndrome, also known as Mucopolysaccharidosis Type VII (MPS VII), is an inherited lysosomal storage disorder caused by a deficiency in the enzyme beta-glucuronidase. As of now, the primary approved treatment is enzyme replacement therapy.

For compassionate use and off-label or experimental treatments, the following options may be considered:

1. **Gene Therapy**: Experimental gene therapies aim to correct the underlying genetic defect by delivering a functional copy of the affected gene.

2. **Substrate Reduction Therapy**: This approach involves reducing the production of the substrates that the deficient enzyme would normally break down, potentially lowering the burden on the body. It is still in early research stages for MPS VII.

3. **Stem Cell Therapy**: Hematopoietic stem cell transplantation (HSCT) is being investigated as a possible treatment to replace the deficient enzyme-producing cells.

4. **Chaperone Therapy**: This experimental treatment uses small molecules to stabilize the defective enzyme, enhancing its functionality. It's still in the research phase for MPS VII.

5. **Gene Editing**: Techniques like CRISPR/Cas9 are being explored for correcting the genetic mutations responsible for Sly syndrome, though these are still largely in experimental phases.

These treatments are largely investigational and may be available to patients only through clinical trials or special compassionate use programs. Always consult medical specialists for the most current and personalized treatment options.
Lifestyle Recommendations: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is a rare genetic disorder. Specific lifestyle recommendations for individuals with Sly syndrome include:

1. **Regular Medical Follow-up**: Regular visits to a multi-disciplinary team of specialists, including geneticists, cardiologists, pulmonologists, and orthopedic surgeons, to manage and monitor symptoms and complications.

2. **Physical Therapy**: Engaging in physical therapy to maintain mobility and muscle strength, which can be affected by the disease.

3. **Occupational Therapy**: Occupational therapy can help children and adults with daily living activities and improve their quality of life.

4. **Balanced Diet**: A balanced diet suitable for individual needs can help maintain overall health, although no specific diet is known to alter the course of the disease.

5. **Exercise**: Moderate, low-impact exercise can help maintain joint function and mobility. Activities like swimming can be particularly beneficial.

6. **Respiratory Care**: Use of respiratory therapies and devices if needed to manage breathing difficulties.

7. **Avoiding Infections**: Minimize the risk of infections, as individuals may be more susceptible due to potential respiratory issues.

8. **Supportive Footwear and Orthotics**: Use of supportive footwear or orthotic devices to manage walking difficulties and support joint function.

9. **Education and Social Support**: Providing appropriate educational support and encouraging social interactions to enhance cognitive development and emotional well-being.

10. **Pain Management**: Effective management of pain, which could include medications or other therapies, as advised by healthcare professionals.

These recommendations should be tailored to the specific needs and circumstances of the individual with Sly syndrome. Regular consultation with healthcare providers is essential for individualized care planning.
Medication: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), does not have a definitive cure but can be managed with various treatments. Specific medications for managing symptoms or complications include enzyme replacement therapy (ERT) with vestronidase alfa (brand name Mepsevii). Other treatments may include supportive care, such as physical therapy, pain management, and surgical interventions for complications like spinal cord compression or hernias.
Repurposable Drugs: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is a rare genetic disorder caused by a deficiency of the enzyme beta-glucuronidase. This enzyme deficiency leads to the accumulation of glycosaminoglycans (GAGs) in various tissues.

**Repurposable Drugs:**
- **Aldurazyme (Laronidase):** While primarily used for MPS I, this enzyme replacement therapy could theoretically have benefits for other types of MPS, including MPS VII.
- **Idursulfase (Elaprase):** Originally for MPS II, some therapeutic overlap may exist due to the similarities in GAG accumulation.
- **Ataluren (Translarna):** This drug is designed to help produce functional protein in cases of nonsense mutations, and it's being investigated for applicability in other genetic disorders.

Consultation with a healthcare provider and clinical trials can offer more personalized and up-to-date options.
Metabolites: Sly syndrome, also known as Mucopolysaccharidosis Type VII (MPS VII), involves the accumulation of glycosaminoglycans (GAGs) such as dermatan sulfate, heparan sulfate, and chondroitin sulfate. This accumulation occurs due to a deficiency in the enzyme beta-glucuronidase, which is responsible for breaking down these GAGs.

Could you clarify what you mean by "nan"?
Nutraceuticals: Sly Syndrome, also known as MPS VII (Mucopolysaccharidosis type VII), is a rare genetic disorder caused by a deficiency of the enzyme beta-glucuronidase. There is limited information on the use of nutraceuticals specifically for treating Sly Syndrome. Treatment typically focuses on enzyme replacement therapy (ERT) and supportive care to manage symptoms.

Regarding nanotechnology, research into nanomedicine offers potential future avenues for treatment, such as targeted drug delivery systems and gene therapy, but these are still largely experimental and not yet standard care for Sly Syndrome.
Peptides: Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is a rare genetic disorder caused by a deficiency in the enzyme beta-glucuronidase. This enzyme deficiency leads to the accumulation of glycosaminoglycans (GAGs) in various tissues. As of now, peptide therapies specifically targeting Sly syndrome are not widely established. However, enzyme replacement therapy (ERT) and other approaches like gene therapy are being explored in clinical trials to manage this condition.