Lesch Nyhan Syndrome or LNS is a rare disorder, which runs in families. It is observed in males and is present since birth. The disorder is characterized by increased production of uric acid, which is normally found in blood and urine and some neurological and behavioral abnormalities. The abnormally increased uric acid levels can further lead to other medical problems.
Causes of Lesch Nyhan Syndrome
Lesch Nyhan syndrome is caused by a defect in a gene that controls the production of an enzyme called hypoxanthine-guanine phosphoribosyl transferase (HPRT), which is responsible for proper metabolism of purines. Purines are involved in a person's genetic makeup and are a building block of a person's DNA.
Proper recycling of purines is essential to ensure steady supply of these building blocks for production of genes. The lack of this enzyme (HPRT), affects the way purines are recycled and their functioning. This results in building up of abnormally high levels of uric acid, which can lead to other health problems.
Lesch Nyhan Syndrome is caused by a genetic defect on the X- chromosome, hence it is an X-linked genetic disorder. It is transferred from mother to son and as the son bears only one X-chromosome, which is defective, he suffers from the condition.
Signs & Symptoms of Lesch Nyhan Syndrome
The main areas affected in Lesch Nyhan Syndrome are the neurological functioning, behavioral and cognitive abilities and excess uric acid or hyperuricemia.
Overproduction of uric acid increases its level in blood (hyperuricemia). If this remains unnoticed and untreated, excess uric acid can lead to:
- Uric acid crystals or stone formation in kidneys, ureters or bladder. This causes increased risk of urinary infection and at time causes hematuria. Crystals and hematuria appear like orange sand on baby nappies.
- Crystals may also get deposited in some joints, which can cause swelling, tenderness and gout like arthritis.
Neurological impairment mainly presents as low muscle tone and delayed developmental milestones like sitting, crawling, walking, etc during the first year. In older babies spasms of facial muscles and limbs may be seen. Sometimes, difficulty in swallowing and even lack of speech may be noted.
Some other features include, irritability, loss of motor control, abnormal jerking movements of limbs, arching of spine, overactive or increased reflexes and spasticity. Affected persons may have difficulty in walking, may require assistance in these activities and may even have to use a wheelchair.
Behavioral disturbances, often seen later are mainly characterized by self injurious behavior like biting or head banging. These actions that inflict self harm may be noted or increased during times of stress. The self mutilating behavior is a keynote feature of Lesch Nyhan Syndrome and is seen in almost all cases. This self destruction may increase with time and become severe and more like a compulsion. Other behavior issues include being aggressive, non-cooperative and responding coldly or with anger.
Diagnosis of Lesch Nyhan Syndrome
Diagnosis of Lesch Nyhan Syndrome can be made by a detailed case history and thorough examination of the patient. Blood and urine tests are done to detect increased uric acid levels. Blood tests may also reveal microcytic anemia.
Clinical examination to assess neurological functioning, behavioral problems and cognitive abilities are performed. Along with the typical clinical features, the physician may be able to elicit increased reflexes and spasticity. Physical examination to assess growth may reveal, delayed growth and development, learning difficulties, delayed or absent puberty and testicular atrophy.
The three main characteristics, uric acid overproduction, neurological impairment and behavioral problems are typical to make a diagnosis of Lesch Nyhan Syndrome. Exact diagnosis can be obtained by performing tests to study the enzyme activity and genetic testing to find the defect.
Treatment of Lesch Nyhan Syndrome
Lesch Nyhan Syndrome, being a genetic disorder, it does not have treatment to cure the disorder. However, certain medications may be used for reducing symptoms,
- Allopurinol to manage increased uric acid levels or gouty arthritis.
- Drugs like diazepam, haloperidol or gabapentin are sometime used for behavioral problems, spastic and related issues.
- Appropriate intervention is done to treat urinary stones.
- Surgical approach may be considered for muscular and joint complaints.
A normal healthy diet and activity is generally advised. It is important to ensure proper hydration and have increased intake of fluids to reduce the risk of urinary stones.
Physical restraints may be required to prevent major injuries from head banging and biting. Behavior modification techniques and other rehabilitation therapies may be helpful in managing behavioral and cognitive difficulties.
Prevention of Lesch Nyhan Syndrome
Persons with family history of Lesch Nyhan Syndrome should have genetic counseling before planning for a child. Women related to Lesch Nyhan Syndrome patients, like mothers, sisters should be screened to detect if they are carriers. Prenatal screening can be done for pregnant women who are carriers of Lesch Nyhan Syndrome or those who have a history of delivering a child with Lesch Nyhan Syndrome.