Hunter disease
Hunter disease, also known as Mucopolysaccharidosis Type II (MPS II), is a progressive genetic disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (I2S). This condition leads to the abnormal accumulation of mucopolysaccharides in various organs, affecting multiple systems in the body, including the brain, joints, and heart. It predominantly affects male children due to its X-linked recessive inheritance pattern, with an estimated prevalence of 1 in 100,000 to 170,000 males in the United States. Symptoms typically emerge in early childhood and can include distinctive facial features, joint stiffness, respiratory issues, and developmental delays, with significant variability in severity and progression among individuals.
Diagnosis is often based on clinical symptoms, supplemented by biochemical tests to confirm enzyme levels and genetic testing for the IDS gene. While there is currently no cure for Hunter disease, treatment focuses on enzyme replacement therapy and managing specific symptoms through medical care and surgeries as needed. Genetic counseling and carrier testing are available for families affected by the condition, as it is inherited and cannot be prevented. Life expectancy can vary widely, with severe cases resulting in early mortality, while milder forms may allow individuals to live into adulthood.
Hunter disease
ALSO KNOWN AS: Mucopolysaccharidosis Type II; MPSII; iduronate 2-sulfatase deficiency
DEFINITION Hunter disease is a progressive inherited disorder caused by the abnormal storage of specific sugar molecule chains. This storage affects the appearance and function of every body system including the brain, face, joints, bones, liver, spleen, lungs, airway, and heart.
Risk Factors
Hunter is a lysosomal storage disease caused by the inheritance of the nonworking IDS gene from both parents. The disease almost exclusively occurs in male children, with the Cleveland Clinic estimating the condition affected 1 out of every 100,000 to 170,000 males in the United States. The condition is panethnic and occurs all over the world. This disease is genetic and cannot be transmitted by an affected individual.
Etiology and Genetics
Hunter disease is caused by the lack of an known as iduronate-2-sulfatase (I2S) in a small cellular organelle called the lysosome. The lysosome is the recycling center of the cell. When I2S is missing, the body cannot break down and recycle specific material called mucopolysaccharides or glycosaminoglycans (GAGs). The decreased amount of enzyme occurs when the gene IDS located on the X chromosome is changed and not working. The buildup of GAGs over time in the organs of the body result in the symptoms of Hunter disease.
Hunter disease is an X-linked recessive condition that primarily affects male children. When a condition is X-linked, the gene for the condition travels through the family on the X chromosome. Chromosomes are the structures which contain our genetic information and are the instructions for making our body. Females have two X chromosomes, while males have a single X chromosome and a Y chromosome. In other words, females receive two copies of the genetic information stored on the X chromosome. When a female inherits the gene for an X-linked recessive condition, she is known as a carrier. She most frequently has no problems related to that condition, because the gene on her other X chromosome continues to function properly and “masks” the abnormal gene. However, males only inherit one copy of the information stored on the X chromosome. When a male inherits the gene for an X-linked recessive condition, he will experience the symptoms associated with that condition. In X-linked genetic conditions, the risk for a carrier female to have an affected son is 50 percent, while the risk to have a carrier daughter is also 50 percent. Having said this, there are very rare cases of females affected by Hunter disease due to unusually functioning X chromosome genes.
Symptoms
Hunter disease is a systemic disease that affects the whole body. Early signs of Hunter disease that can be seen in affected babies include abnormal bone formation, frequent respiratory infections, and an enlarged abdomen. Affected children rarely have the characteristic facial features of Hunter disease at birth. The features of Hunter disease appear gradually over the first years of life and may include: distinguished facial features with prominent forehead and flattened nasal bridge, large head, decreased hearing, enlarged tonsils and adenoids, joint contractures, further abnormal bone formation, swollen abdomen, enlarged spleen and liver, hernias, heart valve issues, breathing difficulties, short stature, developmental delays, and a range of brain involvement.
There is significant variability in both age of onset and rate of progression of affected individuals. Some children have a milder form of Hunter disease which is called attenuated Hunter disease. More seriously affected individuals are diagnosed with severe Hunter disease. Without treatment Hunter disease symptoms in all forms progressively worsens over time. Life expectancy can be difficult to predict and can range from childhood into adulthood.
Screening and Diagnosis
The initial diagnosis of Hunter disease is often suspected based on the physical features of the affected individual. The presence of Hunter disease is then confirmed through biochemical testing including levels of the enzyme I2S in the blood and heparan and dermatan sulfate in the urine. Molecular testing can also provide important information about the disease causing changes in the IDS gene. Prenatal diagnosis and carrier testing are available through molecular testing at specialized laboratories.
Treatment and Therapy
As of the early 2020s, there was no cure for Hunter disease. Treatment of Hunter disease requires a combination of enzyme replacement therapy and medical care of each symptom individually. Physical, developmental, and occupational therapies can assist with optimizing function. Surgeries are often required for treatment of many disease manifestations including removal of tonsils and adenoids, hip replacements, hernia repairs, and many other surgeries. Individuals affected by Hunter disease can have significant problems with general anesthesia due to their narrowed airways.
Prevention and Outcomes
Hunter disease is a genetic condition; accordingly there are no specific ways to prevent being affected by Hunter disease. Carrier testing is available for individuals who are interested in learning if they carry an altered IDS gene. Genetic counseling is available for parents who have an affected child and individuals who are concerned about being a carrier of a nonworking IDS gene.
Although the severity and symptoms of Hunter disease vary from individual to individual, in its severe form, untreated children often die before ten years of age. In its milder form, affected individuals can live a fairly normal life span.
Bibliography
Gonick, Larry, and Mark Wheelis. The Cartoon Guide to Genetics. New York: Collins, 1991.
Hashmi, Mydah S., and Vikas Gupta. "Mucopolysaccharidosis Type II." StatPearls, 25 July 2023, www.ncbi.nlm.nih.gov/books/NBK560829/. Accessed 6 Sept. 2024.
"Hunter Syndrome." Cleveland Clinic, 27 July 2023, my.clevelandclinic.org/health/diseases/17932-hunter-syndrome. Accessed 6 Sept. 2024.
Willett, Edward. Genetics Demystified. New York: McGraw-Hill, 2005.