Hunter’s disease belongs to the mucopolysaccharidoses (MPS). It is inherited in an x-linked recessive manner and therefore affects almost only boys and men. The course of the disease varies among patients.
What is Hunter disease?
Hunter disease is a hereditary lysosomal storage disorder in which the degradation of dermatan and heparan sulfate is impaired. Both polymers are macromolecules consisting of a polysaccharide chain with a sulfate residue. This molecule is still bound to a glucoprotein. The polysaccharides are composed of different simple sugars. Dermatan sulfate is involved in the formation of cartilage tissue. Heparan sulfate takes over important tasks in the extracellular area. In Hunter’s disease, these macromolecules are either not degraded or insufficiently degraded. Since the compounds are first taken up by the lysosomes before degradation, degradation disorders lead to a constant accumulation of the substances in these cell organelles. The disease occurs very rarely. Only one case occurs per 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 its severity. Cases with physical, motor and mental retardation occur. However, there are also milder cases that are so treatable that the symptoms can almost be repressed.
Causes
Hunter’s disease is caused by a mutation on the X chromosome. In this case, 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 the cleavage of the sulfate group from dermatan and heparin sulfate. This degradation therefore no longer occurs or does not occur to a sufficient extent. In this process, the two polymers are stored in the lysosomes. This leads to enlargement of the lysosomes and finally to destruction of the affected cells. The inheritance of the disease is x-linked recessive. This means that almost only boys and men can contract the disease. Girls and women have two X chromosomes. Since the gene is recessively inherited, one healthy gene is sufficient to prevent the disease. However, boys and men have only one X chromosome and one Y chromosome, so if the defective gene is inherited, there is no compensation from a healthy gene.
Symptoms, complaints, and signs
Hunter’s disease is manifested by various symptoms. Thus, on the one hand, there are cases with severe mental retardation and, on the other hand, very mild courses without mental impairment. Life expectancy may be reduced. However, there are also cases with normal life expectancy. Pale, nodular thickenings of the skin often occur. In these cases, the thickenings usually stand together in groups. Other symptoms include thick eyebrows, protruding lower jaw, enlarged tongue, sunken nose root or fleshy lips. The voice is deep and hoarse. Furthermore, hearing loss may occur. The joints deform progressively and skeletal changes occur. The abdomen is distended, and liver and spleen enlargement may develop. Growth retardation and umbilical hernias are other symptoms. Paralysis of all four limbs may also occur. The heart is also affected. This can result in heart failure. Heart failure is the leading cause of death when the disease is severe. The symptoms are caused by the enlargement of the cells due to the constant storage of dermatan and heparan sulfates in the lysosomes of the cells. The disease can already affect children and adolescents (type A). Then it usually comes to a severe course 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 also transitional forms between the two types. The success of treatment also depends on the severity of the disease.
Diagnosis and course of the disease
Hunter’s disease is diagnosed by laboratory tests. This involves urinalysis for the mucopolysaccharides dermatan sulfate and heparan sulfate. Determination of the defective enzyme is performed in leukocytes or fibroblasts. Molecular genetic analysis can also be performed. In this case, the leukocyte DNA is determined. Prenatal diagnosis of the corresponding mutation is also possible.Because the disease is progressive, regular pulmonary function tests, echocardiograms, and orthopedic follow-up are necessary.
Complications
Hunter’s disease primarily causes very severe mental retardation in patients. For this reason, affected individuals are almost permanently dependent on the help of other people. It is not uncommon for relatives or parents to suffer from psychological complaints, upsets or severe depression as a result of this disease. Furthermore, the patients also suffer from hearing loss and visual problems. It is not uncommon for changes to occur in the skeleton, resulting in limitations in various movements. The growth and development of the child are significantly delayed and restricted by Hunter’s disease, so that severe restrictions and complications occur, especially in adulthood. Furthermore, this disease not infrequently 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. Through various therapies or through the transplantation of stem cells, some complaints can be limited. However, the success and further course of treatment strongly depends on the severity of Hunter’s disease, so that a positive course of the disease is not achieved in every case. However, complications do not occur during treatment.
When should you go to the doctor?
Since in Hunter’s disease, due to the genetic cause, almost exclusively boys and men belong to the risk group of the disease, parents should be especially vigilant with their male offspring. If the symptoms do not appear until adulthood, men should undergo a comprehensive examination as early as possible. Preferably, participation in regular check-ups for early detection is advisable. If a child shows growth delays or developmental disorders, a visit to the doctor is recommended. If mental limitations or delays are noted in direct comparison to children of the same age, a visit to the doctor should be made. Specific tests will reveal discrepancies and can be clarified. If there are abnormalities in the appearance of the skin, a formation of lumps on the skin or discoloration, a doctor should be consulted. Umbilical hernias, paralysis or further restrictions of mobility should be clarified immediately. The general risk of accidents and injuries is increased in Hunter’s disease. Therefore, complications should be minimized as early as possible and a visit to the doctor should be made. If daily tasks can no longer be performed as usual or only with the help of others, a doctor should be consulted. If the affected person suffers from emotional or mental problems, a visit to the doctor is also recommended. Medical help is needed for mood swings or depressive phases.
Treatment and therapy
Causal treatment of Hunter’s disease is not possible because it is a genetic disorder. The success of therapy varies from patient to patient. It also depends on the severity. In some cases, stem cell transplantation can be successfully performed. Since 2007, the drug idursulfase with the trade name Elaprase has been approved in Europe. Idursulfase, as iduronate-2-sulfatase, represents the enzyme that is no longer functional in Hunter’s disease. In some cases, good results are achieved by the enzyme treatments. Normal life expectancy can be achieved by this therapy. The treatment must be lifelong. In far advanced cases, however, sometimes no therapy is promising. In this case, it is necessary to alleviate the symptoms.
Outlook and prognosis
The prognosis for affected individuals is highly individual and varies depending on the current severity. Because the disease is purely hereditary, Hunter’s disease has yet to be cured. Newly researched forms of therapy, such as a transplantation of hematopoietic stem cells or gene therapy, can theoretically cure the disease, but they are still considered experimental at the moment. The course of the disease is highly variable from patient to patient. However, if the disease remains untreated, it can lead to death before the patient reaches the age of five in severe cases.Even in the milder forms, many patients die before they reach adulthood. However, especially non-neuronopathic types of Hunter’s disease can be treated very well by means of an enzyme replacement therapy as well as together with the therapy of the occurring disease symptoms. Since the cause of the disease is a genetic defect, affected couples who wish to have children should seek advice from a genetic consultation. An amniocentesis and a chorionic villus sampling can also be performed during pregnancy to determine whether the gene for Hunter’s disease is defective in the offspring. The life expectancy of those with the disease is normal to limited. Among these, mortality is due to cardiopulmonary complications in most of the cases.
Prevention
Prevention of Hunter disease is not possible. It is a hereditary disease. If there are previous cases of this disease in the family and there is a desire to have children, human genetic counseling should be sought to assess the risk. Prenatal genetic testing is also possible. If the disease already exists, it is important to have complete examinations. Therapy should begin early to successfully manage the disease.
Follow-up
Hunter’s disease is a hereditary disease and has no cure to date. The course of the disease is very individual depending on its severity, 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 sporting activity can have a positive influence on the general condition. Gentle sports such as gymnastics and swimming help to maintain or even improve the mobility of the affected limbs. Psychological complaints increase in the course of the disease and can be treated psychotherapeutically. In Hunter’s disease, medical emergencies such as acute heart failure may occur frequently. In the event of an emergency typical of this disease, it is essential to call the emergency medical services. Until the emergency physician arrives, first responders should provide first aid and, if necessary, perform resuscitative measures. Hunter’s disease is fatal sooner or later, depending on its severity. Comprehensive therapeutic treatment, supplemented by a healthy lifestyle and discussions with other sufferers, can improve the quality of life of those with the disease. As a rule, it helps sufferers to cope better with their disease if they are sufficiently informed about symptoms, complaints, causes and consequences. Regular discussions with a specialist are also part of the therapy. Medical advice supports sufferers in their daily management of Hunter’s disease.
What you can do yourself
Hunter’s disease is not curable so far. Patients can nevertheless take some measures to alleviate the symptoms and improve their well-being. For neurological symptoms, exercise is a good option in addition to therapy and physical therapy. Swimming as well as aerobics help to improve the mobility of the affected limbs. Increasing psychological complaints are worked through in the course of psychotherapy. In the event of acute heart failure or another emergency typical of the disease, the emergency medical services must be called. Until the emergency physician arrives, first responders must provide first aid to the affected person and, if necessary, attempt resuscitation. Hunter’s disease is usually fatal. This makes comprehensive therapeutic treatment, supported by discussions with other sufferers and a healthy and active lifestyle, all the more important. Sufferers are often better able to cope with the disease after they have obtained detailed information about the symptoms, complaints, causes and consequences. Especially in the early stages of the disease, regular consultations with a specialist are therefore essential. The physician can give further tips on how the patient can support the treatment of Hunter’s disease.
