Lesch-Nihan syndrome is classified as a hereditary disease associated with metabolic disorders. The disease manifests itself from the first months of life. It is dangerous because there is no specific therapy against it. Treatment helps only to stabilize the condition, but not to heal the child completely by eradicating the cause. What are the features of this pathology? What is the likelihood of developing such a syndrome?
Definition
Among the rare disorders of purine metabolism, Lesh-Nihan pathology is distinguished. The syndrome is more common in boys, as it is linked to the X chromosome. It is associated with enzyme deficiency, as a result of which the metabolism of uric acid is disturbed, its amount increases. The accumulation of this substance is manifested by a number of neurological and metabolic manifestations, on the basis of which the disease can be suspected. The strange behavior of the baby requires a medical examination, which includes the collection of general tests and genetic examination.
Etiology
What is the Lesch-Nihan syndrome connected with? The causes of this pathology lie in genetic disorders. This means that the presence of a recessive gene in the mother leads to the development of pathology - the defect is sex-linked. The development process is described in more detail below. Moreover, the presence of such a gene does not always lead to the development of the syndrome - the probability is 25%. In order to assess the risk of developing pathology, medical genetic counseling is recommended.
Genetic disorder
Lesch-Nyhan syndrome (recessive, sex-linked inheritance type) is a severe hereditary disease. It is associated with damage to the HPRT (hypoxanthine-guanine phosphoribosyltransferase) gene, which is located on the X chromosome - on its long arm. Women have two such chromosomes, and men have one, which is why a genetic disorder is more common in the stronger sex. Cases of the development of the syndrome in women are quite rare, and its appearance can be explained by the inactivation of the X chromosome.
Biochemical features
In connection with enzymatic disorders, the Lesch-Nyhan syndrome manifests itself. Its biochemistry consists in a deficiency of hypoxanthine-guanine phosphoribosyltransferase. Under normal conditions, this enzyme is present in all cells, but more of it is found in the neurons of the brain. A genetic disorder leads to its absence, resulting in impaired hypoxanthine metabolism. Due to this, an excessive amount of uric acid is formed, which is detected in urine and blood tests. Exactlytherefore, patients develop symptoms of gout.
Cerebrospinal fluid has features. It increases the level of hypoxanthine, not uric acid. This causes neurological abnormalities, and uric acid is not able to pass through the blood-brain barrier. The etiology of behavioral disorders has not yet been established. Scientists do not associate it with an excess of hypoxanthine and uric acid. It is believed that hyperuricemia leads to a lack of dopamine. An increased sensitivity of D1 receptors located on striatal neurons is formed. This can lead to increased aggression.
Clinical manifestations
Genetic disorders are linked to how the Lesch-Nyhan syndrome manifests itself. Symptoms of pathology primarily reflect damage to the nervous system. Patients are concerned about a pronounced convulsive syndrome, while convulsions capture individual muscle groups. Hyperkinesias are also common, manifested by twitching of the limbs as a result of a spontaneous increase in muscle tone. Children with this syndrome lag behind both in physical and mental development: their speech is slurred, possibly a late onset of walking. The impact on the function of the vagus nerve leads to an increase in the gag reflex: the emptying of the stomach occurs without any reason. In addition, paralysis and epileptic seizures are not uncommon. The disease is associated with metabolic disorders, resulting in specific manifestations. During the day, as a rule, a large amount of urine is excreted, whichassociated with constant thirst and renal pathology. Uric acid accumulates in the earlobes, leading to the formation of so-called tophi. In the urine, uric acid crystals are found that have an orange color. In addition, joints, usually small ones, are involved in the process. They develop an inflammatory process - arthritis.
Behavior
Does Lesha-Nihan disease affect lifestyle and habits? The syndrome seriously changes the patient's behavior due to damage to the central nervous system. The child becomes very restless, his mood is constantly changing. Particularly noteworthy are attacks of aggression that can occur for no reason at any time. Such children have a tendency to self-harm, that is, they inflict bites and scratches on themselves. This is what is considered a characteristic symptom of pathology. Even the preservation of full pain sensitivity does not stop patients. They may scream in pain, but continue to injure themselves.
Diagnosis
The diagnosis of "Lesch-Nyhan syndrome" (photos of patients are presented in the article) is based on a clinical examination and special additional research methods. Three main symptom complexes will help to suggest pathology. Pay attention to muscle disorders of a convulsive nature, a tendency to self-harm and polyuria. Injury to oneself plays a special role, which should alert parents. After identifying the symptoms, the child is sent for a urine and blood test. Biochemistry will allowdetermine the level of uric acid in these body fluids. It is also necessary to make a genetic examination, which will confirm the diagnosis. An ultrasound of the kidneys is recommended to detect pathology in them. After confirming the disease, the child is registered with a neurologist and rheumatologist.
Treatment
Pharmacological and non-drug methods help to correct the Lesch-Nyhan syndrome. Treatment is aimed at preventing complications and improving the condition. To reduce the risk of kidney failure, it is necessary to reduce the level of uric acid, which is achieved by Allopurinol. The use of "Diazepam" is recommended to calm the patient and eliminate attempts to injure himself. Other sedatives may be taken. In addition to this, constant monitoring of behavior is necessary. With aggressive attacks, the appointment of "Risperidone" is possible. In addition, stressful situations should be excluded. This will help the patient to adapt to his environment and come into close contact with other people. The support of relatives is an integral factor that will help correct behavior. Swaddling or soft gloves are recommended to protect against self-harm. Previously, they often resorted to the extraction of teeth in order to exclude bites. At the moment, the development of medicine, in particular dentistry, allows the use of special plates that are put on the teeth without causing discomfort to the patient.
Complications
Like most pathologies, Lesch-Nihan disease also has complications. The syndrome can lead to consequences associated with the accumulation of uric acid and hypoxanthine. These violations reduce life expectancy and do not allow normal adaptation in society. Significant disorders include arthritis and nephrolithiasis.
Inflammation of the joints is associated with the deposition of uric acid. The accumulation of its crystals has a destructive effect on cartilage and its environment. As a rule, the joints of the feet and hands are affected. In the area of inflammation, soreness and hyperemia appear. Pain increases with movement.
Nephrolithiasis (or kidney stones) can lead to complications such as pyelonephritis. The renal pelvis is involved in the inflammatory process. The infection can spread by the hematogenous or urinogenous route and affect the tissue and interstitium. With the transition of inflammation to the chronic stage, the processes of irreversible sclerosis are triggered. The development of pathology leads to the formation of severe renal failure. Particularly dangerous is the replacement of the structural elements of the kidney with connective tissue, this is what irreversibly disrupts its function - the release of substances unnecessary to the body.
This is the peculiarity of Lesh-Nihan's pathology. The syndrome is completely incurable. Therapy is aimed at reducing clinical manifestations and stabilizing the condition. The patient's environment and living conditions play a big role in this.
