Hunter's Syndrome (MPS-2)
Deficiency in the lysosomal enzyme responsible for the breakdown of glycosaminoglycans (GAGs).
Note: Dysostosis multiplex refers to a constellation of symptoms including hepatosplenomegaly, marked skeletal abnormalities, short stature, and a deformed thoracic cage.
About
- Hunter's syndrome (Mucopolysaccharidosis Type II, MPS-2) is a rare genetic disorder.
- It belongs to the group of disorders known as Mucopolysaccharidoses (MPS) , which are characterized by the inability to break down glycosaminoglycans (GAGs).
- It is a rare condition, affecting fewer than 1 in 100,000 individuals.
- Hunter’s syndrome is inherited in an X-linked recessive manner, meaning it primarily affects males (other MPS disorders are autosomal recessive).
Aetiology
- Caused by a deficiency of the enzyme iduronate-2-sulfatase (I2S), which is needed to degrade GAGs such as dermatan sulfate and heparan sulfate.
- This enzyme deficiency leads to the accumulation of GAGs in various tissues, causing progressive damage to multiple organ systems.
Clinical Features
- Coarse facial features (coarse facies): Enlarged head, broad nose, full lips, and thickened skin.
- Dysostosis multiplex: Skeletal deformities, including short stature, joint stiffness, and deformities of the thoracic cage and spine.
- Mental retardation: Progressive intellectual disability is common, although there is a milder form with normal intelligence.
- No corneal clouding: Unlike some other MPS disorders, Hunter’s syndrome does not typically cause corneal clouding.
- Cardiopulmonary complications: Cervical myelopathy, chronic obstructive pulmonary disease (COPD), and cor pulmonale (right-sided heart failure due to lung disease) can develop over time.
- Death in adolescence: The severe form of the disease often leads to death in adolescence due to complications like respiratory failure.
- Milder form: In the less severe form, individuals may have normal intelligence and survive into adulthood, but still face significant physical challenges.
Investigations
- Genetic testing: Identifies mutations in the IDS gene, which encodes the iduronate-2-sulfatase enzyme, confirming the diagnosis.
- Urinary GAG levels: Elevated levels of glycosaminoglycans in the urine are a common finding.
- Enzyme assay: Measures the activity of iduronate-2-sulfatase in blood or skin fibroblasts to confirm the enzyme deficiency.
- Imaging studies: X-rays and MRI can be used to assess skeletal abnormalities (dysostosis multiplex) and monitor the progression of organ involvement.
Management
- Supportive care: Management focuses on symptomatic treatment, including:
- Shunting for hydrocephalus: If fluid builds up around the brain, a shunt may be needed to relieve pressure.
- Joint replacement: May be necessary in cases of severe joint stiffness or immobility.
- Physical therapy to maintain mobility and manage joint stiffness.
- Enzyme replacement therapy (ERT): Idursulfase (Elaprase) is available for treating MPS II. It helps slow disease progression but does not cure the disease.
- Gene therapy: Experimental treatments are being developed, aiming to correct the underlying genetic defect.
- Monitoring: Regular follow-up is needed to monitor for complications such as respiratory problems, cardiac issues, and progressive skeletal changes.