Hunter ‘s disease is one of the mucopolysaccharidoses (MPS). It is inherited in an x-linked recessive manner and therefore almost exclusively affects boys and men. The disease progression of the individual patients is different.
What is Hunter’s disease?
Hunter’s disease is a hereditary lysosomal storage disease in which the breakdown of dermatan and heparan sulfate is disrupted. Both polymers are macromolecules made up of a polysaccharide chain with a sulfate residue. This molecule is still attached to a glucoprotein. The polysaccharides are made up of different simple sugars. See homethodology for Claw Hand Overview.
Dermatan sulfate is involved in the formation of cartilage tissue. Heparan sulfate takes on important tasks in the extracellular area. In Hunter’s disease, these macromolecules are either not broken down or only broken down insufficiently. Since the compounds are first taken up by the lysosomes before they are broken down, there is a constant accumulation of the substances in these cell organelles in the event of breakdown faults.
The disease occurs very rarely. There is only one case in 156,000 births. For Germany, this results in only four to five cases per year. Almost only boys and men are affected. The course of the disease varies greatly depending on the severity. There are cases of physical, motor and mental retardation. However, there are also milder cases that can be treated so well that the symptoms can almost be suppressed.
Causes
Hunter’s disease is caused by a mutation on the X chromosome. The gene for the synthesis of the enzyme iduronate-2-sulfatase is defective. The enzyme is either not synthesized at all or only with a limited effect. Iduronate-2-sulfatase is responsible for splitting off the sulfate group from dermatan and heparin sulfate. This degradation therefore no longer takes place or to an insufficient extent.
The two polymers are stored in the lysosomes. The lysosomes enlarge and eventually destroy the affected cells. The inheritance of the disease is x-linked recessive. This means that almost only boys and men can get sick. Girls and women have two X chromosomes. Because the gene is recessive, a healthy gene is enough to prevent the disease. However, boys and men only have one X chromosome and one Y chromosome, so if the defective gene is inherited, there is no compensation for a healthy gene.
Symptoms, Ailments & Signs
Hunter’s disease manifests itself through a variety of symptoms. On the one hand there are cases with severe mental retardation and on the other hand there are very mild forms without mental limitations. Life expectancy can be reduced. But there are also cases with normal life expectancy. Pale, nodular thickening of the skin often occurs. The thickenings are mostly in groups.
Other symptoms include thick eyebrows, a protruding lower jaw, an enlarged tongue, a sunken bridge of the nose, or fleshy lips. The voice is deep and hoarse. Deafness can also occur. The joints deform progressively and skeletal changes occur. The abdomen is distended, and enlargement of the liver and spleen may develop.
Growth retardation and umbilical hernias are other symptoms. Paralysis of all four limbs can also occur. The heart is also affected. This can lead to heart failure. Heart failure is the main cause of death when the disease progresses severely. The symptoms arise from the enlargement of the cells due to the constant storage of the dermatan and heparan sulfates in the lysosomes of the cells.
The disease can already affect children and adolescents (type A). Then there is usually a severe form with mental retardation. Sometimes, however, the disease does not begin until adulthood (type B). In this case, the course is often very mild. However, there are transitional forms between the two types. The success of the treatment also depends on the severity of the disease.
Diagnosis & course of disease
Hunter’s disease is diagnosed by laboratory tests. Urine analyzes are carried out for the mucopolysaccharides dermatan and heparan sulfate. The defective enzyme is determined in the leukocytes or in the fibroblasts. A molecular genetic analysis can also be carried out. The leukocyte DNA is determined.
Prenatal diagnosis of the corresponding mutation is also possible. Since the disease is progressive, regular lung function tests, echocardiographies and orthopedic follow-up checks are necessary.
Complications
Patients with Hunter’s disease primarily experience very severe mental retardation. For this reason, those affected are almost permanently dependent on the help of other people. It is not uncommon for relatives or parents to experience psychological problems, upsets or severe depression as a result of this disease.
The patients also suffer from hearing loss and visual problems. It is not uncommon for changes in the skeleton to occur, resulting in limitations in various movements. The growth and development of the child are significantly delayed and restricted by Hunter’s disease, so that there are severe restrictions and complications, especially in adulthood.
Furthermore, this disease often leads to heart problems, so that those affected suffer from a greatly reduced life expectancy due to sudden cardiac death. A causal treatment is not possible in this case. Some complaints can be reduced by various therapies or by transplantation of stem cells.
However, the success and further course of treatment depends heavily on the severity of Hunter’s disease, so that the disease does not always progress positively. However, there are no complications during the treatment.
When should you go to the doctor?
Since boys and men are almost exclusively in the risk group for the disease due to the genetic cause of Hunter’s disease, parents should be particularly vigilant when it comes to their male offspring. If the symptoms only appear in adulthood, men should undergo a comprehensive examination as early as possible. Participation in regular check-ups for early detection is advisable. If a child shows growth retardation or developmental disorders, a doctor’s visit is recommended. If mental limitations or delays are found in a direct comparison to children of the same age, a doctor should be consulted.
Targeted tests uncover discrepancies and can be clarified. A doctor should be consulted in the event of abnormalities in the complexion, formation of lumps on the skin or discolouration. Umbilical hernias, paralysis or other restrictions on mobility must be clarified immediately. The general risk of accidents and injuries is increased with Hunter’s disease.
Therefore, complications should be minimized and a doctor’s visit should be made as early as possible. If everyday tasks can no longer be carried out as usual or can only be carried out with the help of others, a doctor should be consulted. If the person concerned suffers from emotional or psychological problems, a visit to the doctor is also recommended. Medical help is needed for mood swings or periods of depression.
Treatment & Therapy
A causal treatment of Hunter’s disease is not possible because it is a genetic disease. The success of a therapy varies from patient to patient. It also depends on the severity. In some cases, a stem cell transplant can be successfully performed. The drug idursulfase has been approved in Europe under the trade name Elaprase since 2007.
As iduronate-2-sulfatase, idursulfase is the enzyme that is no longer functional in Hunter’s disease. In some cases good results are achieved with the enzyme treatments. With this therapy, a normal life expectancy can be achieved. The treatment must be lifelong. In advanced cases, however, therapy is sometimes no longer promising. The aim here is to alleviate the symptoms.
Outlook & Forecast
The prognosis for those affected is very individual and varies depending on the current degree of severity. Since the disease is purely hereditary, there is still no cure for Hunter’s disease. Newly researched forms of therapy, such as a transplantation of hematopoietic stem cells or gene therapy can theoretically heal, but they are currently considered experimental. The course of the disease is very variable from patient to patient.
However, if the disease remains untreated, it can lead to death before the age of five in severe cases. Even with the milder forms, many of the patients die before they reach adulthood. However, non-neuronopathic types of Hunter’s disease in particular can be treated very well using enzyme replacement therapy and together with therapy for the symptoms of the disease that occur.
Since the cause of the disease is a genetic defect, affected couples who wish to have children should seek advice in a genetic consultation. An amniocentesis test and a chorionic villus biopsy can also be used during pregnancy to determine whether the gene for Hunter’s disease is defective in the offspring. The life expectancy of those affected is normal to limited. In most cases, mortality is due to cardiopulmonary complications.
Prevention
It is not possible to prevent Hunter’s disease. It is a hereditary disease. If cases of this disease have already occurred in the family and there is a desire to have children, genetic counseling should be sought in order to be able to assess the risk. Prenatal genetic testing is also possible. If the disease already exists, it is important to have thorough examinations carried out. Therapy should start early in order to be able to successfully accompany the disease.
Aftercare
Hunter’s disease is a hereditary disease and there is currently no cure. Depending on the severity, the course of the disease is very individual, but patients require lifelong treatment. In order to alleviate symptoms and improve general well-being, those affected can take some measures themselves.
In the case of neurological complaints, targeted physiotherapy and physical activity can have a positive effect on the general condition. Gentle sports such as gymnastics and swimming help to maintain or improve the mobility of the affected limbs. Mental health problems increase as the disease progresses and can be treated with psychotherapy.
Medical emergencies such as acute heart failure can often occur in Hunter’s disease. In an emergency typical of this disease, the emergency services must be called. Until the arrival of the emergency doctor, the first responders should provide first aid and, if necessary, carry out resuscitation measures. Depending on the severity, Hunter’s disease is fatal sooner or later.
Comprehensive therapeutic treatment, supplemented by a healthy lifestyle and talking to other sufferers, can improve the patient’s quality of life. As a rule, it helps those affected to deal better with their illness if they are sufficiently informed about the symptoms, complaints, causes and consequences. Regular consultations with the specialist are also part of the therapy. Medical advice supports sufferers in dealing with Hunter’s disease on a daily basis.
You can do that yourself
There is currently no cure for Hunter’s disease. However, patients can take some measures to relieve the symptoms and improve their well-being.
In addition to therapy and physiotherapy, physical activity is also an option for neurological complaints. Swimming and aerobics help improve mobility in the affected limbs. The increasing psychological complaints are processed within the framework of psychotherapy. In the event of acute heart failure or another emergency typical of the disease, the emergency services must be called. Until the emergency doctor arrives, the first responders must provide first aid to the person concerned and, if necessary, also attempt resuscitation.
Hunter’s disease is usually fatal. All the more important is a comprehensive therapeutic treatment, which is supported by discussions with other affected people and a healthy and active lifestyle. Patients can often deal with the disease better after they have informed themselves in detail about the symptoms, complaints, causes and consequences. Regular consultations with a specialist are therefore essential, especially in the early stages of the disease. The doctor can give further tips on how the patient can support Hunter’s disease therapy.
