Lesch-Nyhan syndrome is a rare hereditary disease caused by a defective gene on the X chromosome. Symptoms occur in varying degrees and affect both the body and the mind. Lesch-Nyhan syndrome cannot be cured; only the symptoms can be alleviated.
What is Lesch-Nyhan syndrome?
Lesch-Nyhan syndrome is a rare inherited disorder that results in a metabolic disorder due to a gene defect. The altered gene causes a deficiency of the enzyme HGPRT, which is needed for purine metabolism. As a result of the disorder, uric acid in the body increases and the uric acid level in the blood rises (hyperuricemia). Gout develops with deposits of uric acid crystals in tendons, joints, skin and in cartilage. The deposits also form in the central nervous system and cause disorders there. Lesch-Nyhan syndrome occurs only very rarely; in Germany, only about 30 – 40 people are affected. As a rule, only males become ill. Women are usually only carriers of the defective gene and pass it on to their offspring. Only if the altered gene is present twice, i.e. in the homozygous state, would women become ill. Lesch-Nyhan syndrome is also called hyperuricemia syndrome or primary childhood gout.
Causes
The cause of Lesch-Nyhan syndrome is a genetic defect that is inherited in an x-linked recessive manner. This means that the mutated gene is located on the X chromosome, one of the two sex chromosomes. Recessive means that someone who has inherited only one defective gene remains healthy if the other gene of the second parent is intact. This also explains why mainly men are affected by Lesch-Nyhan syndrome. Females have sex chromosomes XX, while males have XY, i.e. only one X. If female individuals inherit a diseased X from one of their parents, they are still left with the healthy X, which can fully perform all functions. If male individuals receive a diseased X, the disease breaks out because there is no other healthy X left. In females, Lesch-Nyhan syndrome would only develop if they inherited a diseased X chromosome from both parents, which is extremely rare.
Symptoms, complaints, and signs
Although Lesch-Nyhan syndrome is a congenital disorder, symptoms do not appear until six to eight weeks after birth. Before then, at most, yellowish urine residue in the diapers of affected newborns indicates a serious condition. The first clear sign of Lesch-Nyhan syndrome is the urge to vomit. Affected babies vomit several times a day, often resulting in deficiencies and dehydration. After ten months, other symptoms begin to appear: Noticeable leg deformities, a reduced urge to move, and developmental delays. Parents also notice that the child cannot walk and does not perform natural movements. In the mildest form of the disease, there are also elevated uric acid levels, which can result in gout later in life. As the disease progresses, urinary tract infections and kidney stones may also form. The more severe form can be recognized by the deformities mentioned above. The second most severe form can be noticed by the characteristic self-injurious behavior of the children. Affected individuals bite and scratch their lips and fingers, which can lead to bleeding, inflammation and other symptoms. In the most severe form, self-mutilation occurs, along with severe mental impairment. Affected children are aggressive, constantly biting each other and often attacking parents and caregivers.
Diagnosis and course
The symptoms of Lesch-Nyhan syndrome are not present immediately after birth, but develop during the first few weeks of life. From the sixth to eighth week, frequent vomiting is noticeable and urine residues are found in the diapers, caused by increased excretion of uric acid. In the further months, typical signs of Lesch-Nyhan syndrome appear. The children move little and they lag behind in their development, both physically and mentally. They do not learn to sit or walk and they cannot coordinate their movements properly. They are delayed in learning to speak and can only concentrate for short periods of time. The most striking symptom, however, is the uncontrollable compulsion to bite, injuring or even maiming themselves.However, this behavior occurs only in severe manifestations of the disease. In the milder form of Lesch-Nyhan syndrome, only uric acid increases, leading to gout over the years. The diagnosis is made by first looking at the symptoms and measuring the uric acid level in the blood. Final certainty as to whether Lesch-Nyhan syndrome is present is provided by genetic testing.
Complications
As a result of Lesch-Nyhan syndrome, affected individuals suffer from both psychological and physical symptoms and limitations. Usually, the patient’s quality of life is significantly reduced and limited by this syndrome. There is vomiting and a reduced urge to move. Furthermore, those affected suffer from an unusual position of the legs, and bullying or teasing may occur, especially at a young age. Furthermore, mental disorders occur, so that especially children suffer from underdevelopment and have to expect complaints in adulthood. Not infrequently, patients are then dependent on the help of other people in their daily lives and are unable to do many things on their own. Furthermore, self-mutilation may occur, which can lead to psychological discomfort or depression, especially for relatives and parents. Likewise, patients often appear aggressive or irritable, so that social restrictions may occur. Lesch-Nyhan syndrome is treated by various therapies and by taking medication. However, a positive course of the disease cannot be guaranteed in every case. Patients may then be dependent on treatment for the rest of their lives.
When should one go to the doctor?
If the child shows signs of Lesch-Nyhan syndrome, a doctor should be consulted promptly. For example, the pediatrician must be informed if the child vomits frequently one to two months after birth and generally suffers from increasing malaise. If other symptoms and complaints become apparent, such as a conspicuous leg position or a reduced urge to move, a doctor must be consulted. Lesch-Nyhan syndrome is a serious hereditary disease that results in severe complications if left untreated. The affected children suffer from severe movement restrictions and behavioral disorders despite early therapy, which is why close contact with the family doctor and a physiotherapist is necessary even beyond treatment. In addition, the patients often require psychological care. Any abnormalities in the behavior of those affected must be carefully worked through and reduced as part of behavioral therapy. Depending on the symptoms, the patient may also need to see a urologist, gynecologist, gastroenterologist or nephrologist. In case of seizures and other medical emergencies, the rescue service is the right contact.
Treatment and therapy
Therapy for Lesch-Nyhan syndrome is primarily directed at the symptoms, since the cause of the disease, the genetic defect, is not treatable. Thus, drugs are administered which lower the urine level and the diet is low in purines. Furthermore, a high fluid intake must be ensured. These measures are intended to prevent or at least reduce uric acid deposits in the body and the associated impairments. Uric acid levels must be checked regularly. Furthermore, precautions must be taken regarding self-injurious behavior. Sedative medications such as diazepam (e.g., Valium) but also neuroleptics such as haloperidol have been used successfully in Lesch-Nyhan syndrome. At night, sleeping pills are sometimes administered to allow patients to have reasonably quiet nights. However, therapeutic measures depend on how severe the manifestation of Lesch-Nyhan syndrome is.
Outlook and prognosis
Lesch-Nyhan syndrome has an unfavorable prognosis. A disposition of human genetics is present that leads to a metabolic disorder. Current legislation does not allow intervention to alter human genetic makeup. Therefore, the cause of the health disorder cannot be eliminated. The symptoms and irregularities already occur in the first weeks of life. In the entire developmental and growth process of the diseased person, a variety of impairments or delays become apparent. The cognitive performance is reduced and behavioral disorders appear.If left untreated, the symptoms of the disease lead to a severe reduction in quality of life. There is a possibility of self-harm as well as an increased risk of injury to others. Therefore, medical treatment is inevitable for an improved course of the disease. Long-term therapy and the administration of medications are required. Immediately after stopping the medication, the symptoms return within a short time. Although the disease cannot be cured, the symptomatically occurring abnormalities can be well controlled and monitored in a therapy. Despite all efforts, freedom from symptoms is not achieved. In addition to metabolic disorders, the genetic disease also leads to irreparable developmental disorders. If therapies and targeted exercises are carried out with the patient at an early stage, an overall improvement in the quality of life can be observed.
Prevention
Prevention of Lesch-Nyhan syndrome is not possible because it is a hereditary disease caused by a defective gene. If a pregnant woman is known to have the defective gene and is diagnosed with Lesch-Nyhan syndrome in prenatal (before birth) tests, it is possible to terminate the pregnancy.
Follow-up
In many inherited diseases, follow-up is also very difficult in Lesch-Nyhan syndrome. Genetic defects or mutations can have such serious consequences that medical professionals can mitigate, correct, or treat only a few of them. In many cases, hereditary diseases cause severe disabilities. Those affected have to struggle with these for the rest of their lives. What can be done in aftercare often enough consists only of physiotherapeutic or psychotherapeutic measures. However, treatment successes can be achieved for a whole series of slowly progressive hereditary diseases. In the case of Lesch-Nyhan syndrome, follow-up care goes hand in hand with the type of treatment aimed at controlling the metabolic disorder. Accordingly, medication is aimed at bringing uric acid levels to moderate levels. The type of diet, which may amount to a special diet, also plays a major role. Generalized statements about the type of aftercare are only permissible to the extent that life is made easier for the affected patients if possible. Hereditary diseases can cause increasing or consistently severe symptoms throughout life. They can considerably limit the quality and length of life. For many hereditary diseases, surgery provides little relief. Postoperative follow-up may be necessary. Some of the symptoms or disorders of hereditary diseases can be successfully treated nowadays. Psychotherapeutic care is useful for hereditary diseases where depression, feelings of inferiority, or other psychological disorders occur as a result of the characteristics of the disease.
What you can do yourself
In Lesch-Nyhan syndrome, treatment focuses on lowering the elevated uric acid concentration in the blood. This is accomplished by medications containing the active ingredient allopurinol, accompanied by lifestyle changes. At the beginning of the therapy, the doctor will suggest a diet to the patient or refer him to a nutritionist. Together with the specialist, a diet plan can be drawn up, ideally consisting of a low-purine diet and regular fluid intake. Regular exercise and the avoidance of stress can be important factors in improving lifestyle and permanently lowering the uric acid concentration in the blood. If children are affected, parents must take further measures to stop the self-injurious behavior. For example, it may be necessary to restrain the child or put a helmet on him or her as head protection. In severe cases, the incisors must be removed to prevent the typical self-mutilation. Many patients also require intensive psychotherapeutic care. Since the disease is usually a considerable burden for the parents as well, family therapy can be useful. The therapist can often also establish contact with other affected parents.
