Which are the causes of Hunter syndrome?

Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), is a rare genetic disorder that primarily affects males. It is caused by a deficiency of the enzyme iduronate-2-sulfatase (I2S), which is responsible for breaking down certain complex molecules called glycosaminoglycans (GAGs). The deficiency of this enzyme leads to the accumulation of GAGs in various tissues and organs of the body, resulting in a wide range of symptoms.

Genetic Mutation: Hunter syndrome is an X-linked recessive disorder, meaning it is caused by a mutation in the gene located on the X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome. Since the gene responsible for producing the I2S enzyme is located on the X chromosome, males are more commonly affected by the disorder. If a female carries the mutated gene, she is considered a carrier and can pass it on to her children.

Enzyme Deficiency: The primary cause of Hunter syndrome is the deficiency of the I2S enzyme. This deficiency occurs due to mutations in the IDS gene, which provides instructions for producing the enzyme. Without sufficient levels of I2S, the body cannot effectively break down GAGs, leading to their accumulation in various tissues.

Accumulation of Glycosaminoglycans: GAGs are long chains of sugar molecules that are essential for the normal functioning of cells and tissues. However, in individuals with Hunter syndrome, the accumulated GAGs interfere with the normal functioning of organs and tissues, causing progressive damage over time.

Progressive Nature: Hunter syndrome is a progressive disorder, meaning that symptoms worsen over time. The severity of the disease can vary widely among affected individuals, even within the same family. The accumulation of GAGs affects multiple systems in the body, including the skeletal system, respiratory system, cardiovascular system, central nervous system, and others.

Signs and Symptoms: The symptoms of Hunter syndrome can manifest in early childhood or later in life, depending on the severity of the disease. Common signs and symptoms include developmental delays, coarse facial features, enlarged liver and spleen, joint stiffness, skeletal abnormalities, hearing loss, respiratory problems, heart valve abnormalities, and cognitive impairment.

Diagnosis: Hunter syndrome is typically diagnosed through a combination of clinical evaluation, genetic testing, and enzyme activity assays. The presence of characteristic physical features, along with elevated levels of GAGs in urine or blood, can raise suspicion of the disorder. Genetic testing can confirm the presence of mutations in the IDS gene, while enzyme activity assays can measure the levels of I2S enzyme in the body.

Treatment: Currently, there is no cure for Hunter syndrome. However, various treatment options are available to manage the symptoms and improve the quality of life for affected individuals. Enzyme replacement therapy (ERT) involves regular infusions of the missing I2S enzyme to help break down GAGs. Other supportive therapies, such as physical therapy, speech therapy, and surgery, may also be recommended to address specific symptoms and complications.

Conclusion: Hunter syndrome is a rare genetic disorder caused by a deficiency of the I2S enzyme, leading to the accumulation of GAGs in various tissues and organs. The progressive nature of the disease and its wide range of symptoms make early diagnosis and intervention crucial for managing the condition. Ongoing research and advancements in treatment options offer hope for improved outcomes and better quality of life for individuals with Hunter syndrome.