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Mucopolysaccharidosis Ii

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Description: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare genetic disorder caused by a deficiency of the enzyme iduronate-2-sulfatase, leading to the accumulation of glycosaminoglycans in various tissues and organs.
Type: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is transmitted in an X-linked recessive pattern.
Signs And Symptoms: Hunter syndrome may present with a wide variety of phenotypes. It has traditionally been categorized as either "mild" or "severe" depending on the presence of central nervous system symptoms, but this is an oversimplification. Patients with "attenuated" or "mild" forms of the disease may still have significant health issues. For severely affected patients, the clinical course is relatively predictable; patients will normally die at an early age. For those with milder forms of the disease, a wider variety of outcomes exist. Many live into their 20s and 30s, but some may have near-normal life expectancies. Cardiac and respiratory abnormalities are the usual cause of death for patients with milder forms of the disease.The symptoms of Hunter syndrome (MPS II) are generally not apparent at birth. Often, the first symptoms may include abdominal hernias, ear infections, runny noses, and colds. As the buildup of GAGs continues throughout the cells of the body, signs of MPS II become more visible. The physical appearance of many children with the syndrome include a distinctive coarseness in their facial features, including a prominent forehead, a nose with a flattened bridge, and an enlarged tongue. They may also have a large head, as well as an enlarged abdomen. For severe cases of MPS II, a diagnosis is often made between the ages of 18 and 36 months. In milder cases, patients present similarly to children with Hurler–Scheie syndrome, and a diagnosis is usually made between the ages of 4 and 8 years.The continued storage of GAGs leads to abnormalities in multiple organ systems. After 18 months, children with severe MPS II may experience developmental decline and progressive loss of skills. The thickening of the heart valves and walls of the heart can result in progressive decline in cardiac function. The walls of the airway may become thickened, as well, leading to obstructive airway disease. As the liver and spleen grow larger with time, the abdomen may become distended, making hernias more noticeable. All major joints may be affected by MPS II, leading to joint stiffness and limited motion. Progressive involvement of the finger and thumb joints results in decreased ability to pick up small objects. The effects on other joints, such as hips and knees, can make walking normally increasingly difficult. If carpal tunnel syndrome develops, a further decrease in hand function can occur. The bones themselves may be affected, resulting in short stature. In addition, pebbly, ivory-colored skin lesions may be found on the upper arms, legs, and upper back of some people with it. These skin lesions are considered pathognomonic for the disease. Finally, the storage of GAGs in the brain can lead to delayed development with subsequent intellectual disability and progressive loss of function.The age at onset of symptoms and the presence or absence of behavioral disturbances are predictive factors of ultimate disease severity in very young patients. Behavioral disturbances can often mimic combinations of symptoms of attention deficit hyperactivity disorder, autism, obsessive compulsive disorder, and/or sensory processing disorder, although the existence and level of symptoms differ in each affected child. They often also include a lack of an appropriate sense of danger, and aggression. The behavioral symptoms of MPS II generally precede neurodegeneration and often increase in severity until the mental handicaps become more pronounced. By the time of death, most children with severe MPS II have severe mental disabilities and are completely dependent on their caretakers.
Prognosis: Earlier onset of symptoms is linked to a worse prognosis. For children who exhibit symptoms between the ages of 2 and 4, death usually occurs by the age of 15 to 20 years. The cause of death is usually due to neurological complications, obstructive airway disease, and cardiac failure. If patients have minimal neurologic involvement, they may survive into their 50s or beyond.
Onset: Mucopolysaccharidosis II, also known as Hunter syndrome, typically has an onset in early childhood, often between 2 to 4 years of age. The rate at which symptoms appear and progress can vary significantly, with more severe forms presenting earlier and more rapidly.
Prevalence: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, has an estimated prevalence of approximately 1 in 100,000 to 1 in 170,000 live births. It primarily affects males. The condition is caused by a deficiency of the enzyme iduronate-2-sulfatase, leading to the accumulation of glycosaminoglycans in various tissues and organs.
Epidemiology: An estimated 2,000 people have MPS II worldwide, 500 of whom live in the United States.A study in the United Kingdom indicated an incidence among males around one in 130,000 male live births.
Intractability: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is generally considered an intractable disease in terms of a definitive cure. Current treatments, such as enzyme replacement therapy (ERT) with idursulfase, can alleviate some symptoms and improve quality of life but do not halt disease progression entirely. Additionally, bone marrow transplantation has limited efficacy and significant risks. Research is ongoing for gene therapy and other advanced treatments, but as of now, MPS II remains a challenging condition to completely cure.
Disease Severity: Mucopolysaccharidosis II, also known as Hunter syndrome, has a variable disease severity. It can range from mild to severe, affecting multiple organs and bodily systems. In severe cases, it can lead to profound intellectual disability, skeletal abnormalities, heart valve problems, respiratory issues, and a markedly reduced life expectancy. Milder forms may present with fewer cognitive issues and allow for a longer, relatively more functional life. The disease severity is typically determined by the extent of enzyme deficiency and resultant accumulation of glycosaminoglycans.
Healthcare Professionals: Disease Ontology ID - DOID:12799
Pathophysiology: The human body depends on a vast array of biochemical reactions to support critical functions. One of these functions is the breakdown of large biomolecules. The failure of this process is the underlying problem in Hunter syndrome and related storage disorders.The biochemistry of Hunter syndrome is related to a problem in a part of the connective tissue known as the extracellular matrix, which is made up of a variety of sugars and proteins. It helps to form the architectural framework of the body. The matrix surrounds the cells of the body in an organized meshwork and functions as the glue that holds the cells of the body together. One of the parts of the extracellular matrix is a molecule called a proteoglycan. Like many components of the body, proteoglycans need to be broken down and replaced. When the body breaks down proteoglycans, one of the resulting products is mucopolysaccharides (GAGs).In MPS II, the problem concerns the breakdown of two GAGs: dermatan sulfate and heparan sulfate. The first step in the breakdown of dermatan sulfate and heparan sulfate requires the lysosomal enzyme iduronate-2-sulfatase, or I2S. In people with MPS II, this enzyme is either partially or completely inactive. As a result, GAGs build up in cells throughout the body, particularly in tissues that contain large amounts of dermatan sulfate and heparan sulfate. The rate of GAGs buildup is not the same for all people with MPS II, resulting in a wide spectrum of medical problems.
Carrier Status: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a genetic disorder linked to the X chromosome. As such, carrier status primarily pertains to females. A female who carries one mutated copy of the IDS gene is a carrier. Carriers typically do not exhibit symptoms of the disease but can pass the mutated gene to their offspring. For male offspring, there is a 50% chance of having MPS II, and for female offspring, there is a 50% chance of being a carrier.
Mechanism: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare genetic disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (I2S). This enzyme is crucial for the degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate. The absence or reduced activity of I2S leads to the accumulation of these GAGs in various tissues and organs, resulting in progressive damage.

**Mechanism:**
1. **Enzyme Deficiency:** Mutations in the IDS gene, located on the X chromosome, lead to either a nonfunctional or absent I2S enzyme.
2. **GAG Accumulation:** The inability to break down dermatan sulfate and heparan sulfate results in their accumulation within lysosomes of cells.
3. **Cell and Tissue Damage:** The buildup of GAGs interferes with normal cellular function and leads to progressive tissue and organ damage.

**Molecular Mechanisms:**
1. **Genetic Mutation:** Point mutations, deletions, or other alterations in the IDS gene reduce or eliminate the production of functional I2S enzyme.
2. **Impaired Lysosomal Activity:** Lysosomes, which rely on I2S to degrade GAGs, accumulate undigested GAGs, leading to cellular dysfunction.
3. **Secondary Effects:** The storage of GAGs in cells triggers a cascade of secondary cellular and molecular responses, contributing to inflammation, fibrosis, and the generation of reactive oxygen species.

This disruption at the molecular level manifests as a wide range of symptoms including developmental delay, organomegaly, and skeletal abnormalities.
Treatment: Because of the wide variety of phenotypes, the treatment for this disorder is specifically determined for each patient. Until recently, no effective therapy for MPS II was available, so palliative care was used. Recent advances, though, have led to medications that can improve survival and well-being in people with MPS II.
Compassionate Use Treatment: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare, genetic lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. For patients with MPS II, several treatment options might be considered under compassionate use, off-label, or experimental categories.

1. **Compassionate Use Treatment**:
- **Idursulfase (Elaprase)**: This enzyme replacement therapy (ERT) is the standard treatment and might be provided under compassionate use for patients who do not have access to it through standard healthcare channels.

2. **Off-Label Treatments**: Off-label treatments for MPS II are relatively uncommon due to the specificity of the disease, but some supportive treatments may be used to manage symptoms, such as:
- **Hematopoietic Stem Cell Transplantation (HSCT)**: While more commonly associated with other conditions, HSCT has been attempted in some cases of MPS II to provide a source of enzyme-producing cells.

3. **Experimental Treatments**:
- **Gene Therapy**: This is an emerging area for MPS II treatment. Clinical trials are ongoing to evaluate the safety and efficacy of gene therapy aimed at correcting the underlying genetic defect.
- **Substrate Reduction Therapy (SRT)**: Experimental drugs are being investigated to reduce the accumulation of glycosaminoglycans (GAGs) by inhibiting their synthesis.
- **New Enzyme Replacement Therapies**: Enhanced forms of ERT, which aim to improve outcomes by increasing enzyme delivery to affected tissues, are also under investigation.

Participation in clinical trials and consultation with a specialist in metabolic genetic disorders can provide access to these experimental therapies.
Lifestyle Recommendations: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a genetic disorder that affects the body's ability to break down specific complex sugars. Here are some lifestyle recommendations for managing this condition:

1. **Regular Medical Care**: Regular check-ups with a healthcare provider experienced in MPS II are crucial for managing symptoms and complications.

2. **Enzyme Replacement Therapy (ERT)**: Patients often receive ERT to help manage symptoms and improve quality of life. Adherence to the prescribed treatment schedule is important.

3. **Physical Therapy and Exercise**: Engaging in appropriate physical therapy can help maintain joint function and mobility. Gentle exercises are often recommended to improve flexibility and strength.

4. **Diet and Nutrition**: A balanced diet that supports overall health is important. Some patients may need dietary modifications to address specific gastrointestinal issues.

5. **Monitoring Respiratory Health**: Regular monitoring and management of respiratory function is critical, as MPS II can affect lung capacity and lead to respiratory infections.

6. **Supportive Devices**: Using supportive devices, such as braces or mobility aids, can improve daily functioning and reduce strain on affected joints.

7. **Educational Support**: Children with MPS II may require special educational support to address developmental delays or learning difficulties.

8. **Pain Management**: Work with healthcare providers to establish a plan for managing pain, which may include medications or other therapeutic options.

9. **Psychosocial Support**: Counseling and support groups can be beneficial for patients and families to cope with the emotional and psychological aspects of the disease.

10. **Regular Eye and Ear Check-ups**: Regular visits to an ophthalmologist and audiologist are important to monitor and manage vision and hearing issues.

It's essential for caregivers and patients to work closely with a multidisciplinary team of healthcare providers to tailor these recommendations to their specific needs.
Medication: For mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, the primary treatment available is enzyme replacement therapy (ERT) using idursulfase (brand name Elaprase). This medication helps replace the deficient or malfunctioning iduronate-2-sulfatase enzyme. Regular infusions can help manage some symptoms but do not cure the disease. Researchers continue to explore additional treatments, including gene therapy and other investigational drugs, but these are not yet widely available.
Repurposable Drugs: There are no widely recognized repurposable drugs currently approved for Mucopolysaccharidosis II (MPS II, also known as Hunter syndrome). Treatment typically involves enzyme replacement therapy with idursulfase and symptomatic management. Research into repurposing existing drugs for MPS II is ongoing, but definitive evidence and approvals are still pending.
Metabolites: For Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, the primary metabolites of concern are glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate, which accumulate in tissues due to a deficiency of the enzyme iduronate-2-sulfatase.
Nutraceuticals: Nutraceuticals, often referred to as foods or food products that provide health and medical benefits, have not been established as effective treatments for Mucopolysaccharidosis II (MPS II). MPS II, also known as Hunter syndrome, is a genetic lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Current treatment strategies typically focus on enzyme replacement therapy (ERT) with idursulfase and hematopoietic stem cell transplantation (HSCT).

Nanotechnology-based approaches are being investigated for their potential applications in MPS II. These include nanocarriers for enzyme delivery to improve the effectiveness and targeting of treatments. However, such nanotechnologies are still primarily in the research and development stage and not yet available as standard clinical treatments for MPS II.
Peptides: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is caused by a deficiency of the enzyme iduronate-2-sulfatase (I2S). This leads to the accumulation of glycosaminoglycans (GAGs) in various tissues. Peptide-based therapies are being explored to address the enzyme deficiency or reduce GAG accumulation. Nanotechnology approaches are also being investigated to enhance the delivery and efficacy of these therapies, potentially improving outcomes for patients with MPS II.