Summary about Disease
Iduronate-2-sulfatase deficiency, also known as Hunter syndrome or mucopolysaccharidosis type II (MPS II), is a rare, inherited lysosomal storage disorder. It is caused by a deficiency of the enzyme iduronate-2-sulfatase (I2S), which is needed to break down complex sugar molecules called glycosaminoglycans (GAGs), also known as mucopolysaccharides. The buildup of these GAGs in cells and tissues throughout the body leads to a wide range of symptoms affecting physical and neurological development. Hunter syndrome is X-linked recessive, meaning it primarily affects males.
Symptoms
Symptoms of Hunter syndrome vary widely in severity and age of onset. Common symptoms include:
Skeletal abnormalities: Short stature, joint stiffness, claw hand deformities, dysostosis multiplex (characteristic skeletal abnormalities seen on X-rays).
Facial features: Coarse facial features (thickened lips, broad nose, prominent forehead).
Organ enlargement: Enlarged liver (hepatomegaly) and spleen (splenomegaly).
Respiratory problems: Frequent upper respiratory infections, obstructive airway disease, sleep apnea.
Cardiac issues: Heart valve problems, cardiomyopathy.
Skin: Thickened skin, sometimes with small, ivory-colored papules (skin lesions).
Cognitive impairment: Developmental delays, intellectual disability (severity varies).
Hearing loss: Progressive hearing loss.
Hernias: Inguinal and umbilical hernias.
Gastrointestinal issues: Diarrhea.
Causes
Hunter syndrome is caused by mutations in the IDS gene, which is located on the X chromosome. This gene provides instructions for making the iduronate-2-sulfatase (I2S) enzyme. Mutations in the *IDS* gene lead to a deficiency or absence of functional I2S enzyme. Because the *IDS* gene is on the X chromosome, males, who have only one X chromosome, are more likely to be affected. Females, who have two X chromosomes, can be carriers of the mutation and may or may not exhibit symptoms.
Medicine Used
The primary treatment for Hunter syndrome is enzyme replacement therapy (ERT) with idursulfase (Elaprase). ERT involves intravenous infusions of a synthetic version of the I2S enzyme, which helps break down the accumulated GAGs. Hematopoietic stem cell transplantation (HSCT) can also be considered, particularly in young patients with milder disease. Supportive treatments address specific symptoms and may include:
Surgery to repair hernias, carpal tunnel syndrome, or heart valve problems.
Respiratory support, such as CPAP for sleep apnea.
Physical and occupational therapy to improve mobility and function.
Speech therapy.
Medications to manage pain, infections, and other symptoms.
Is Communicable
No, Hunter syndrome (iduronate-2-sulfatase deficiency) is not communicable. It is a genetic disorder caused by a mutation in the IDS gene and is inherited from parents to their children. It cannot be spread from person to person through any infectious mechanism.
Precautions
While Hunter syndrome itself isn't preventable, some precautions and considerations can help manage the condition and improve the quality of life for affected individuals:
Genetic counseling: Families with a history of Hunter syndrome should seek genetic counseling to understand the inheritance pattern and assess the risk of having affected children.
Early diagnosis and treatment: Early diagnosis and initiation of enzyme replacement therapy (ERT) can help slow the progression of the disease and improve outcomes.
Regular monitoring: Regular monitoring of heart, lungs, liver, and other organ systems is important to detect and manage complications.
Supportive care: Provide supportive care to address specific symptoms and needs, such as physical therapy, occupational therapy, and speech therapy.
Vaccinations: Ensuring the affected individual receives appropriate vaccinations can help prevent infections.
Avoidance of certain medications: Some medications may be contraindicated or require careful monitoring due to potential interactions or adverse effects.
Environmental modifications: Adapt the environment to accommodate physical limitations and ensure safety.
How long does an outbreak last?
Hunter syndrome is not an infectious disease and therefore does not have "outbreaks". It is a chronic, progressive condition that lasts a lifetime. The rate of progression and severity of symptoms vary among individuals.
How is it diagnosed?
Hunter syndrome is diagnosed through a combination of clinical evaluation and laboratory testing. Diagnostic methods include:
Clinical evaluation: Physical examination to assess for characteristic features of Hunter syndrome.
Urine tests: Measuring levels of glycosaminoglycans (GAGs) in urine, which are typically elevated in individuals with Hunter syndrome.
Enzyme assay: Measuring the activity of iduronate-2-sulfatase (I2S) enzyme in blood or skin fibroblasts. A deficiency or absence of I2S activity confirms the diagnosis.
Genetic testing: Analyzing the IDS gene for mutations. Genetic testing can confirm the diagnosis and identify carriers.
Other tests: Additional tests may be performed to assess the severity of the disease and monitor organ function, such as echocardiogram, pulmonary function tests, and liver function tests.
Timeline of Symptoms
The timeline of symptom onset and progression varies depending on the severity of the disease.
Severe form: Symptoms typically appear in early childhood (around 2-4 years of age). Developmental delays, coarse facial features, and skeletal abnormalities become apparent. Cognitive impairment progresses rapidly.
Attenuated (milder) form: Symptoms may appear later in childhood or adolescence. Cognitive impairment may be milder or absent. Individuals with the attenuated form may have a longer lifespan. General Progression:
Early Childhood (2-6 years): Frequent respiratory infections, hernias, developmental delays, enlarged liver and spleen.
Childhood (6-12 years): Progressive joint stiffness, skeletal abnormalities, coarse facial features, hearing loss.
Adolescence/Adulthood: Heart valve problems, respiratory insufficiency, cognitive decline (in severe cases), limited mobility.
Important Considerations
Early Diagnosis is Crucial: Early diagnosis and treatment with ERT can significantly improve outcomes and quality of life.
Variability: The severity and progression of Hunter syndrome can vary widely.
Multidisciplinary Care: Management requires a multidisciplinary approach involving specialists in genetics, cardiology, pulmonology, orthopedics, neurology, and other fields.
Family Support: Hunter syndrome can have a significant impact on families, and support groups and resources are available to provide emotional and practical assistance.
Research: Ongoing research is aimed at developing new and improved treatments for Hunter syndrome, including gene therapy.
Progressive Nature: It is important to understand that even with treatment, Hunter syndrome is a progressive disease, and ongoing monitoring and management are necessary.
Anesthesia Risks: Individuals with Hunter syndrome often have anatomical abnormalities of the airway and other medical issues that require special considerations during anesthesia and surgery.