Males are mostly affected by the uncommon hereditary condition known as Lesch Nyhan syndrome (LNS). It is brought on by a mutation in a gene that codes for the purine metabolism-related enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Substances called purines are found in cell RNA and DNA. Those who have LNS lack or do not have HPRT, which causes the body to produce too much uric acid. Urine contains uric acid, which is a waste product that often dissolves in blood. On the other hand, uric acid builds up in the tissues and blood of those who have LNS, leading to a number of health complications. LNS also causes neurological and behavioral problems by affecting the brain and nervous system. We'll talk about LNS causes, symptoms, diagnosis, treatment, and prevention in this blog article.
Because LNS is inherited as an X-linked recessive trait, a mutation in a gene on the X chromosome is the source of the condition. Among the sex chromosomes that define a person's gender is the X chromosome. Females have two X chromosomes, whereas men have one X and one Y chromosome. Males will develop LNS if they inherit the faulty gene from their mother since they have one copy of the X chromosome. However, because they have a normal copy of the gene on their other X chromosome, females who inherit the mutant gene from either parent will not develop LNS. On the other hand, females who have the mutant gene may pass it on to their sons.
The HPRT gene mutation can be inherited from a carrier mother or it can happen sporadically in certain families without a history of LNS. With every pregnancy of a carrier woman, there is a 50% chance of producing a son with LNS. Having a daughter who carries the gene carries a 50% chance of success. There is a 25% chance of producing a child that is neither impacted nor a carrier.
The symptoms of LNS usually appear in the first year of life, and they vary in severity and type. The main symptoms of LNS are:
Hyperuricemia, or elevated blood uric acid levels, is linked to kidney damage, gout, kidney stones, and urinary tract infections. Gout is a disorder that affects the joints, particularly the big toe, causing pain, edema, and inflammation. Hard uric acid deposits called kidney stones can obstruct the passage of urine from the kidneys. The buildup of uric acid crystals in the kidney tissues can cause damage to the kidneys, impede their functionality, and ultimately result in renal failure. When germs invade the urinary system and produce discomfort and inflammation, urinary tract infections may result.
Neurological issues, including seizures, intellectual incapacity, poor coordination, involuntary muscular movements, and stiffness. Spasms, jerks, twitches, and writhing are examples of involuntary muscular movements. Muscle rigidity can impair movement and cause pain in the neck, trunk, and limbs. Ineffective coordination can impact swallowing, speaking, and balance. Periods of aberrant electrical activity in the brain that can result in convulsions, unconsciousness, and other symptoms are called seizures. A person with an intellectual impairment has difficulties with learning, reasoning, and solving problems.
Behavioral issues include compulsions, anger, irritability, self-harm, and impulsivity. One of the hallmarks of LNS is self-harm, which includes hitting the head or limbs on hard surfaces or biting the lips, tongue, fingers, or other body parts. Beating, biting, kicking, and hurling items are examples of aggression. Crying, yelling, or throwing fits are examples of irritability. Impulsivity can manifest as a lack of thought before acting, as well as trouble waiting or sharing. Repetition of words or behaviors, as well as strict adherence to routines or regulations, are examples of compulsions.
Based on the symptoms, family history, and results of laboratory testing, LNS can be diagnosed. Genetic testing, which can identify the mutation in the HPRT gene, helps validate the diagnosis. Prenatal testing is another method of making the diagnosis before to delivery. This involves analyzing the fetus's DNA from a sample of placenta or amniotic fluid.
The laboratory tests that can help diagnose LNS include:
Blood tests, which can measure the level of uric acid and other substances in the blood. People with LNS have high levels of uric acid and low levels of HPRT enzyme activity in the blood.
Urine tests, which can detect the presence of uric acid crystals and other substances in the urine. People with LNS have high levels of uric acid and low levels of hypoxanthine and xanthine (two purine metabolites) in the urine.
Cerebrospinal fluid (CSF) tests, which can analyze the fluid that surrounds the brain and spinal cord. People with LNS have high levels of uric acid and low levels of hypoxanthine and xanthine in the CSF.
There is no cure for LNS, and the treatment is aimed at managing the symptoms and preventing complications. The treatment may involve a combination of medication, surgery, diet, and supportive care. The treatment options for LNS include:
Medication, which can help reduce the production and accumulation of uric acid in the body, and control the seizures and muscle movements. Some of the medications that can be used to treat LNS are:
Allopurinol, which inhibits an enzyme that converts purines into uric acid, and lowers the level of uric acid in the blood and urine.
Febuxostat, which is similar to allopurinol, but may be more effective and have fewer side effects.
Rasburicase, which is an enzyme that converts uric acid into a more soluble and less toxic substance, and lowers the level of uric acid in the blood and urine.
Anticonvulsants, which are drugs that prevent or reduce the frequency and severity of seizures, such as phenobarbital, phenytoin, carbamazepine, valproic acid, or levetiracetam.
Antispasmodics, which are drugs that relax the muscles and reduce the involuntary muscle movements, such as baclofen, diazepam, or tizanidine.
Surgery can be used to replace the damaged kidneys with a donor kidney or to help remove or eliminate the kidney stones. Kidney stones can be removed via percutaneous nephrolithotomy, which involves putting a tube through the skin into the kidney, or by utilizing sound waves to break them up (lithotripsy). When the kidneys are unable to function effectively, kidney transplantation may be done. To prevent rejection, immunosuppressive medications must be taken for the rest of one's life and a suitable donor must be found.
Diet, which can aid enhance uric acid excretion and decrease purine synthesis and ingestion. items include fruits, vegetables, cereals, dairy products, eggs, and lean meats can all be included in a low-purine diet; items like organ meats, shellfish, alcohol, and yeast should be avoided. A large fluid intake might aid in flushing out the uric acid and diluting the urine. A low-protein diet may assist in lowering uric acid production. Kidney stones can be avoided by eating a low-salt diet.
Supportive care, which can enhance the well-being and quality of life for the individual with LNS and their family. Physical therapy, occupational therapy, speech therapy, special education, behavioral treatment, counseling, and social services are examples of supportive care. Maintaining or enhancing muscle strength, flexibility, and mobility can be facilitated by physical therapy. Occupational therapy can support the growth or improvement of everyday living abilities including grooming, eating, and clothing. Speech therapy can facilitate better swallowing and communication. A proper curriculum and learning environment can be provided with assistance from special education. Self-harm and other behavioral issues can be lessened or modified with the use of behavioral treatment. Counseling can assist in overcoming the psychological and emotional obstacles. Social services can facilitate access to support networks and other resources.
Although LNS cannot be prevented, it can be identified early by prenatal and genetic testing. Genetic testing can determine who is afflicted and who carries the mutant gene. Prenatal testing can identify the fetus's condition and provide the parents the information they need to make decisions. Families impacted with LNS may benefit from knowledge and direction provided by genetic counseling.
