What Is Lesch-Nyhan Disease?
Lesch Nyhan syndrome is a disorder that is characterized by uric acid overproduction in the body as well as neurological and behavioral problems. It mainly affects men. Inflammatory arthritis or gout, kidney and bladder stones, as well as mild cognitive impairment may be the signs and symptoms. Involuntary muscle movements and self-injury are just two examples of neurological and behavioral disorders that might arise. Lesch Nyhan syndrome patients frequently use wheelchairs, cannot sit without assistance, and cannot walk. Lesch Nyhan syndrome is an X-linked recessive condition brought on by mutations in the HPRT1 (Hypoxanthine-guanine phosphoribosyl transferase) gene, which is characterized by its absence or insufficient activity. This disease is a rare inborn defect of purine metabolism, and many foods include purines, which are nitrogen-containing substances, for example, poultry and legumes. In the insufficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase or HPRT, the purines hypoxanthine and guanine are not converted into nucleotides. Lesch-Nyhan syndrome patients have excessively high uric acid levels, and renal and joint sodium urate crystal accumulation is also possible.
One in every 380,000 people has Lesch-Nyhan syndrome, according to statistics. In all populations, this condition is prevalent at a similar frequency.
What Are the Symptoms and Signs Seen in Lesch-Nyhan Disease?
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A movement disorder with a neurological foundation that is characterized by modifications in the speed and coordination of voluntary motions or abnormality in the motion.
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Behavioral abnormality disorder which is a mental health condition characterized by a variety of affective, behavioral, cognitive, and perceptual problems. An intelligence quotient (IQ) between 50 and 69 is considered to be mild intellectual impairment, and a score of 35 to 49 on the intelligence quotient (IQ) is considered to be moderate mental impairment.
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Loss of strength in one side of the body; arm, leg, or occasionally face is seen. Hemiparesis is a relatively modest loss of strength, whereas hemiplegia is a significant or complete loss of strength.
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Repeated episodes of acute inflammatory arthritis involving one or more joints brought on by high blood uric acid levels that crystallize and deposit in tendons, joints, and surrounding tissues.
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A decline is seen in the kidneys' ability to perform their various tasks, including concentrating urine, eliminating wastes, maintaining electrolyte balance, maintaining blood pressure homeostasis, and metabolizing calcium.
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Anemia or a decrease in the volume or hemoglobin concentration of erythrocytes.
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Muscle spasticity is a motor disease characterized by increased muscular tone, enhanced or hyperexcitable tendon reflexes, and a velocity-dependent rise in tonic stretch reflexes which is also observed.
What Causes Lesch-Nyhan Disease?
The HPRT1 gene is mutated in Lesch-Nyhan syndrome. The HPRT1 gene guides the enzyme hypoxanthine phosphoribosyl transferase. Purines, a sort of building material for DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are recycled by this enzyme. Recycling purines ensures that cells have an ample supply of the components needed to make DNA and RNA.
Hypoxanthine phosphoribosyl transferase 1 is severely deficient or completely absent due to HPRT1 gene mutations that cause the Lesch-Nyhan syndrome. Purines are broken down but not recycled when this enzyme is absent, resulting in excessively high levels of uric acid. The lack of the enzyme hypoxanthine phosphoribosyl transferase 1 is connected, for unclear reasons, to low levels of dopamine, a chemical messenger present in the brain. Dopamine is a neurotransmitter that helps the human brain govern both muscle movements and emotional behavior; hence, a lack of dopamine may contribute to the disorder's mobility issues as well as other symptoms. Some HPRT1 gene mutation carriers produce some active enzymes. Lesch-Nyhan variation is claimed to exist in these people. Lesch-Nyhan variation does not involve self-injury and frequently exhibits milder symptoms than Lesch-Nyhan syndrome.
How is Lesch-Nyhan Syndrome Diagnosed?
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A comprehensive clinical assessment, which includes a full patient history and blood testing, may be used to confirm the diagnosis of Lesch-Nyhan syndrome. Blood levels of uric acid are excessively high in children with this condition.
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The diagnosis is confirmed by the lack of the HPRT enzyme in the cells from any tissue. It is possible to identify the precise disease-causing mutation by performing molecular genetic testing for the HPRT1 gene. Molecular genetic testing allows for Lesch-Nyhan syndrome carrier detection. If the disease causing HPRT1 gene mutation has been found in an affected family member, preimplantation genetic diagnosis and prenatal diagnosis may be achievable.
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Enzyme analysis is another method for prenatal diagnosis.
What Is the Treatment for Lesch-Nyhan’s Disease?
The precise symptoms that are present in each person with Lesch-Nyhan syndrome are targeted for treatment. The coordinated and combined efforts of a group of professionals might be necessary throughout treatment.
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Physical therapists, pediatricians, specialists in the diagnosis and treatment of skeletal problems (orthopedists), and other health care providers might need to carefully and thoroughly arrange an afflicted child's treatment.
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Allopurinol is a medication used to treat symptoms brought on by high levels of uric acid and to treat Lesch-Nyhan syndrome-related high levels of uric acid. However, the neurological or behavioral signs of this condition are unaffected by this treatment.
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The neurological issues linked to Lesch-Nyhan syndrome have not been successfully treated with long-term care or pharmacological therapy. For the treatment of spasticity, people have utilized Benzodiazepines or Baclofen. Diazepam might be helpful.
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Behavior modification strategies intended to reduce self-mutilating habits have reportedly proven helpful for people with Lesch-Nyhan syndrome, although actual success is uncommon. Lesch-Nyhan syndrome patients typically require physical restraint at the elbows, chest, and hips to prevent self-injury. Hands remain free when using elbow restraints. Biting of the fingers and lips, which can result in lifelong deformity, can be avoided by wearing an oral prosthetic mouth guard or by having the teeth extracted. Many afflicted people ask for constraints on their own. Some affected people's self-mutilating behaviors may get better or stop as they age.
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Drugs have been used to treat Lesch-Nyhan syndrome-related behavioral problems in some patients. These include Baclofen, Carbamazepine, Gabapentin, and Sodium Valproate. Lesch-Nyhan syndrome symptoms of anxiety can occasionally be treated with Benzodiazepines.
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For the families having children with Lesch-Nyhan syndrome, genetic counseling is advised. Other forms of treatment are supportive and symptomatic.
Conclusion
People who have a rare disease may experience enormous difficulties. A range of pressures that may alter over time is typical for patients and their families. These difficulties could include limited knowledge of the condition and available treatments, economic and financial challenges, alterations to routine roles and activities, social repercussions and seclusion, a variety of thoughts and emotions, and caregiving obligations. Children and adults with rare diseases, as well as the people who care for them, are urged to communicate their demands to the medical staff and ask for the help they need. The medical staff can create a plan of care and can refer patients. Support can come from close friends and family. Organizations for patients and caregivers can aid in social interaction, offer financial and disability help, and provide quick aid over the phone.
