Hunter syndrome

Overview

Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), is a rare, inherited lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. This enzyme is responsible for breaking down complex sugars known as glycosaminoglycans (GAGs). When the enzyme is deficient or absent, GAGs accumulate in the body's cells, leading to progressive damage to various organs and tissues. Hunter syndrome primarily affects males and can range from mild to severe in presentation.

Causes

Hunter syndrome is caused by mutations in the ID2S gene located on the X chromosome. The condition follows an X-linked recessive inheritance pattern, which means it almost exclusively affects males. Females can be carriers of the mutation but usually do not show symptoms. The faulty gene results in a deficiency or complete absence of the iduronate-2-sulfatase enzyme, which leads to the harmful accumulation of glycosaminoglycans in the body.

Symptoms

Symptoms of Hunter syndrome typically appear between ages 2 and 4 and progressively worsen over time. The severity and progression vary, but common symptoms include:

• Coarse facial features (broad nose, thick lips, enlarged tongue)

• Enlarged head (macrocephaly)

• Hearing loss

• Thickened skin and joint stiffness

• Enlarged liver and spleen (hepatosplenomegaly)

• Developmental delays and intellectual disability (in severe forms)

• Respiratory issues and frequent infections

• Heart valve abnormalities

• Short stature and skeletal deformities

The disease can be classified as either an attenuated (milder) or severe form based on the extent of cognitive involvement and rate of progression.

Diagnosis

Diagnosis of Hunter syndrome involves a combination of clinical evaluation, biochemical tests, and genetic analysis. Diagnostic steps may include:

• Urine tests to detect elevated levels of glycosaminoglycans

• Blood tests or skin biopsies to measure iduronate-2-sulfatase enzyme activity

• Genetic testing to identify mutations in the IDS gene

• Imaging studies (e.g., MRI, X-rays) to assess organ and skeletal involvement

• Developmental and cognitive assessments in suspected severe cases

Early diagnosis is crucial for initiating timely interventions and supportive therapies.

Treatment

While there is no cure for Hunter syndrome, several treatments can help manage symptoms and slow disease progression:

• Enzyme Replacement Therapy (ERT): Intravenous administration of idursulfase (Elaprase) to supplement the missing enzyme and reduce GAG buildup

• Supportive therapies: Including physical therapy, occupational therapy, and speech therapy to improve quality of life

• Surgical interventions: Such as hernia repair, airway surgeries, or placement of ventilation tubes for ear infections

• Management of complications: Regular monitoring and treatment of heart, respiratory, and neurological issues

ERT does not cross the blood-brain barrier, so it does not improve neurological symptoms in severe cases. Experimental gene and stem cell therapies are under investigation.

Prognosis

The prognosis for individuals with Hunter syndrome depends on the severity of the disease. In severe forms, life expectancy may be reduced, often into the second decade of life, due to complications involving the heart, lungs, or brain. In milder forms, individuals may live into adulthood and maintain relatively normal cognitive function. Early diagnosis and access to enzyme replacement therapy and multidisciplinary care can significantly improve outcomes and quality of life.