Lesch-Nyhan syndrome: Treatment, symptoms, advice and help
About Lesch-Nyhan syndrome
Lesch-Nyhan syndrome is a very rare disorder. This X-linked disorder is of purine metabolism that results from HPRT deficiency. Absence of HPRT prevents the normal metabolism of hypoxanthine resulting in excessive uric acid production and manifestions of gout. The behaviour disorder is not caused by hyperuricemia or excess hypoxanthine.
This enzyme is normally present in each cell in the body, but its highest concentration is in the brain, especially in the basal ganglia. This syndrome ischaracterized by deficiency of this very metabolic enzyme named ‘hypoxanthine guanine phosphoribosyltransferase’ which is responsible for the metabolism of purine. Purine is a normal constituent of human genetic material (RNA and DNA). It is an inherited disease with progressively disabling complications. The mechanism whereby HPRT deficiency leads to the neurological and behavioural symptoms is unknown.
Lesch-Nyhan syndrome: Incidence, age and sex
Lesch-Nyhan syndrome is present since birth and becomes evident in childhood itself. Almost 1 in 380,000 infants may get affected. It is seen more frequently in boys as compared to girls. The disorder appears in males; occurrence in females in extremely rare. The prevalence of the classic Lesch-Nyhan syndrome has been estimated at 1/100,000 to 1/380,000.
Signs and symptoms of Lesch-Nyhan syndrome: Diagnosis
The clinical features of Lesch-Nyhan syndrome are manifested in childhood itself. The syndrome is characterized by neurological and behavioural problems. There seems to be developmental delay in motor activities accompanied with abnormal tendon reflexes. Behavioural problems include a strange tendency towards self destruction.
At birth, infants with LNS have no apparent neurologic dysfunction. Before the age of 4 months, hypotonia, recurrent vomiting, and difficulty with secretions may be noted. Other clinical manifestations include hyperuricemia, intellectual disability, a dystonic movement disorder that may be accompanied by choreoathetosis and spasticity, dysarthric speech, and compulsive self-biting, usually beginning with the eruption of teeth.
However the most typical feature of Lesch-Nyhan syndrome is deposition of uric acid in certain joints resulting in gout like swelling. Occasionally kidney stones, have also been documented in affected individuals.
A detailed clinical examination may reveal exaggerated tendon reflexes along with other neurological abnormalities. Blood test and urinalysis may reveal increased level of uric acid in body. The presence of dystonia along with self-mutilation of the mouth and fingers suggests Lesch-Nyhan syndrome. The definitive diagnosis requires an analysis of the HPRT enzyme. This is assayed in an erythrocytic lysate. Individuals with classic LNS have near 0% enzyme activity and those with partial variants show value between 1.5% and 60%. Molecular genetic studies of the HPRT gene mutations may confirm diagnosis, and are particularly helpful for subsequent 'carrier testing' in at-risk females such as close family relatives on the female side.
Causes and prevention of Lesch-Nyhan syndrome
Lesch-Nyhan syndrome is a hereditary disorder which results from absence of a metabolic enzyme named ‘hypoxanthine guanine phosphoribosyltransferase’. This results in metabolic imbalance of ‘purine’ thereby resulting in increased level of uric acid. It is an X linked recessive disorder, meaning it requires defective X genes from both the parents in order to cause the disease in a female baby. But a single defective X gene in a male baby is sufficient to cause the disease. Couples with family history of Lesch-Nyhan syndrome are advised to go in for genetic counselling when planning a family.
Lesch-Nyhan syndrome: Complications
Lesch-Nyhan syndrome is a serious disorder which may progress to fatal health concerns resulting in severe disability, requiring intensive supportive care. Self-biting is intense and causes tissue damage and may result in the amputation of fingers and substantial loss of tissue around the lips. Acute renal failure may occur in infancy.
Lesch-Nyhan syndrome: Treatment
Unfortunately the available treatment modalities are not very promising in curing the disease. However they include medications of gout, namely Allopurinol, which may help in reducing the uric acid levels. Symptomatic relief and supportive care plays an important role in managing the condition. Lesch-Nyhan syndrome carries a poor prognosis with most of the affected individuals succumbing to neurological affects of the disease resulting in severe disability. Medical management of this disorder focuses on the prevention of renal failure by pharmacologic treatment of hyperuricemia with high fluid intake , alkali and allopurinol. Self mutilation is reduced through behavior management and the use of restraints, removal of teeth, or both. Diazepam may be helpful for anxiety symptoms, and carbamazepine or gabapentin for mood stabilization. Some centres use a protective mouth guard designed by a dentist.