Makindo Medical Notes

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.