Hunter Syndrome or MPS II is an extremely rare, incurable and an inherited genetic disease which is caused by the absence of an enzyme known as the iduronate-2-sulfatase (I2S). The lack of this enzyme in the body or even the mere malfunctioning of it results in the accumulation of molecules that are harmful to the body. Generally, not apparent at the time of birth, the affected babies do not show any signs or symptoms until probably after the first year of their life.
History & Discovery
Named after the Scottish-Canadian physician and professor of medicine, Charles A. Hunter, the disease was first discovered when Hunter identified it in two brothers in the year 1917. Hunter, who was born in Scotland but moved to Winnipeg, Manitoba in Canada, was working at the Winnipeg General Hospital at that time. According to his research paper submitted to the Royal Society of Medicine, both brothers started walking whilst in their 17th month, albeit late but were generally as fine and healthy as normal boys would be, with the exception of having throat issues such as adenoids and tonsils. Furthermore, as time passed, they started hearing lesser than usual.
The probability of Occurrence & Ethnic Epidemiology
The statistics on Hunter Syndrome only assert its claim as a genuinely rare disease. It affects only about 1 in 170,000 males. Although as rare as it may be but the syndrome has also been diagnosed in females too. According to the statistics, currently, only 2,000 people in the entire world are said to be afflicted, out of which, at least 500 belong from the United States itself, 70 from South Korea, 20 from the Philippines, 6 from Ireland, 2 from New Zealand, 1 each from Saudi Arabia, Iran, Chile, Pakistan, and Palestine.
Causes & Inheritance
Mucopolysaccharides are the binding sugar molecules that essentially construct the connective tissues in our bodies. Mucopolysaccharides also referred to as GAGs, lie in the lysosomes, from where they are excreted via the urine. The iduronate-2-sulfatase (I2S) enzyme is responsible for breaking down these molecules for disposal in a normal person. On the contrary, a person affected with Hunter syndrome does not possess this enzyme. This is the reason as to why the GAGs or mucopolysaccharides molecules in a person with Hunter Syndrome do not find their way out via the urine and start accumulating in the lysosomes which hinders the usual functionality of the tissues, cells, and organs. This results in the clinical features observed in the Hunter Syndrome to develop among affected individuals.
If the mother is a carrier of the disorder, there is a highly likely chance, almost as good as 50% that it may be transmitted to a son as this affliction targets the male population predominantly. On account of this reason, often prenatal testing is recommended among pregnant carriers, whereby a sample extracted from the placenta can be tested to verify whether the defective gene is present or not.
Symptoms, Development & Diagnosis
As mentioned before, symptoms remain undiscovered at birth and may take as long as ages 2 to 4 to be discovered. For making an early diagnosis, however, it is pertinent to observe certain key symptoms that generally include the enlargement of the head also known as macrocephaly, the unusual thickening that may show up at the lips, a deep voice, other skeletal abnormalities and delayed developments in the most basic skills of walking and talking. In addition to these, other symptoms may include flared nostrils and the broadening of the nose, diarrhea, stiffness in the joints and aggressive behavior in the affected individual as a result of these underlying symptoms felt by the individual.
Although visible symptoms are hard to miss and help in the initial diagnosis, however, doctors may opt for additional testing in a medical laboratory to further second their opinions. For this purpose, doctors measure the enzyme activity of the iduronate-2-sulfatase (I2S) as the basic premise behind this testing is to confirm whether this enzyme is present in the first place or not. The method used to detect this is via a urine test for GAGs.
If you notice your child’s facial features or appearance starting to change, book an immediate appointment with a specialist to pursue further testing.
As symptoms start to appear right after infancy, it is highly important to treat this in early childhood in order to prevent any complications.
Science, as advanced as it is right now and equipped with the latest technological tools, still has not been able to find a cure for Hunter Syndrome. At present, treatment relies on merely the mitigation of symptoms and the temporary relief to avoid complications. Some of these methods include the elimination of tonsils that would open the flow of an affected child’s respiratory channel and help avoid congestion. This would also help with better sleep patterns eventually.
There is a highly likely chance of developing a heart condition if the child is affected with Hunter Syndrome. Therefore, it is of paramount importance to monitor any cardiovascular complications that may arise in the wake of this. Heart valves may even be replaced via surgery in order to mitigate chances of a heart failure.
Bones are fragile in children with Hunter Syndrome and healing is a process that does not come naturally to them. Physical therapy is one way to help improve the stiffness but is by no means a permanent solution. A wheelchair may eventually be required to help ease the pain and to counter the effects of a low stamina.
Enzyme therapy is one such treatment that is utilizing man-made enzymes, genetically engineered specially to replace the missing enzymes in a child. The idea is to ease the symptoms of the disease and delay as much damage as possible right from the early stages. The treatment takes place via the use of an IV (intravenous) on a weekly basis.
Gene therapy, another new treatment, is aimed at replacing the very chromosome, that produces the iduronate-2-sulfatase (I2S) enzyme. This could actually become the ultimate remedy for this disease. However, an extensive research is required in this regards to making this practical.
Author: Malik Noureed Awan