Diagnosis and treatment of Lesch Nyhan Syndrome

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How is the Lesch Nyhan Syndrome diagnosed?

The Lesch-Nyhan syndrome is initially diagnosed by the presence of typical characteristic features in children like failure to crawl, involuntary muscle movements and problem walking at normal age. The involuntary muscle movement is basically due to the uric acid excessive production in some cases. Clinically, one can recognize it in the child's diapers in the form of orange sand. The orange color is due to a blood tinge that sticks over the uric acid crystals.


One may not possibly diagnose Lesch-Nyhan syndrome by measuring the uric acid amount in a patient's urine or blood. It can be diagnosed through a blood test by measuring the HPRT enzyme activity. Low activity of this enzyme is suggestive of Lesch-Nyhan syndrome. Another diagnostic alternative for this condition is DNA testing, which is a blood test that detects the genetic mutation of HPRT gene. The findings of DNA testing help to determine a final diagnosis and it also helps to guide the child's family. The child's mother should undergo prenatal testing for all subsequent pregnancies.

The condition can also be diagnosed prenatally through DNA testing by obtaining a fetal tissue sample either by chorionic villus sampling (CVS) or amniocentesis. If the mother carries a mutated HPRT gene, then the fetus should be tested to rule out the condition. Women with a family history of Lesch-Nyhan syndrome or a son with Lesch-Nyhan syndrome are at a higher risk of being carriers. These women should undergo a blood test that includes DNA testing.

The condition can be determined by the physician by performing a physical examination which includes:


Over-exaggerated reflexes

In addition, urine and blood tests may contain high uric acid levels. A skin biopsy may reveal low activity level of the HGP enzyme.

The diagnosis of LNS can be quickly made when an affected person completely develops 3 of these important clinical criteria: overproduction of uric acid, neurologic dysfunction, disturbed behavioral and cognitive function. However, early stage LNS is hard to diagnose as the 3 clinical manifestations do not develop full course. Physicians can easily suspect the condition when an affected child presents with hyperuricemia, in addition to developmental delay. Other diagnostic symptoms include delayed growth in association with hematuria (blood in urine), nephrolithiasis (kidney stone formation) due to uric acid stones.

Sometimes, Lesch-Nyhan syndrome may get diagnosed when a child develops injuries or visible tissue loss due to self-inflicted behavior; however, various other medical conditions are also associated with self-injurious behaviors. The typical characteristic feature of Lesch-Nyhan syndrome is biting the lips, cheeks and fingers; however other behavioral manifestations include head banging, self-injury, and nonspecific self-mutilation. Lesch-Nyhan syndrome is usually diagnosed by a physician when the affected child presents with LNS symptoms like neurological dysfunction and hyperuricemia in conjunction with self-injurious behavior.

What is the treatment for Lesch Nyhan Syndrome?

Currently, the neurological defects of Lesch-Nyhan syndrome are not treatable. LNS is basically managed with symptomatic treatment.The blood uric acid levels can be reduced by medications such as Allopurinol (Zyloprim, Aloprim), which are also indicated to reduce the incidence of gout attacks. Most of the medications are used as a preventive measure to reduce the progression of Lesch-Nyhan syndrome. LNS associated spasticity can be effectively managed with muscle relaxant medications like benzodiazepine tranquilizers and baclofen (Lioresal).

In some cases, affected patients require teeth extractions to avoid self-injury. Self-destructive behaviors can be minimized with physical restraints; however, behavioral modification therapy (BMT) in conjunction to medication therapy is advised in case of patients with serious behavioral problems.

Laser lithotripsy is recommended in case of kidney stones. It is a laser surgery that focuses laser beam over the kidney stones and breaks them using shock waves. The neurological symptoms of LNS have no standard treatment and few neurological symptoms can be relieved with medicines like diazepam, haloperidol, levodopa or carbidopa, and phenobarbital. However, there is no effective treatment for extrapyramidal symptoms of LNS.

LNS treatment is generally aimed at controlling the over-production of uric acid and reducing the associated complications like nephrolithiasis, nephropathy, and gouty arthritis. The allopurinol drug prevents the conversion of oxypurines to uric acid and also reduces the risk of developing kidney stones, arthritic tophi that follows a chronic gout, and nephropathy, which eventually leads to an end stage kidney disease.

Affected children with behavioral problems and self-injurious require a combination of physical, medical, and behavioral interventions. Restraints are effective in reducing the self-mutilation. About 60 percent of them with self-injury behavior benefitted from an effective management technique, teeth extraction. In addition, self-injury can be reduced by 75 percent when restrained.

According to Gary E. Eddey, the effective treatment for LNS patients includes:

1) Use of protective devices;

2) Selective ignoring behavioral technique with activity redirection; and

3) Medication therapy

1) Use of protective devices

Self-injury can be prevented by the application of protective devices such as splints or straps at all times during night time sleeping and while undergoing medical tests. These devices are often referred to protective devices rather than restraints, which are used for patients with other growth disorders in hospitals.

2) Management of behavioral conditions with behavior technique modifications

Many patients with Lesch-Nyhan disease lead an active lifestyle despite being profound motor handicaps. However, serious behavioral problems, including self-injurious behavior are hard to manage. Hence, the combination of medication therapy and behavioral-modification technique is reinforced to manage the condition. Best results can be achieved by the positive reinforcement and behavioral extinction methods. Attenuating problem behavior can be managed with adjunctive drugs, benzodiazepines and gabapentin. Severe conditions are treated with short term neuroleptics.

In addition, serious tissue injury caused by self-injurious biting habits may require dental extraction if not controlled with combination therapy like medical/behavioral therapy. Complications from neurologic manifestations often require orthopedic intervention to treat joint complications, spinal deformity, subluxed joints and to release the contractures.

3) Medication therapy

Hypouricemic agents

Hypouricemic drugs are indicated to reduce hyperuricemia and associated health complications such as gouty arthritis, nephrolithiasis, and subcutaneous tophi. Allopurinol (Zyloprim) drug works by inhibiting the hypoxanthine metabolism and xanthine conversion to uric acid by blocking the function of xanthine oxidase enzyme. This medication improves hyperuricemia condition and reduces the risk of developing related complications.

Febuxostat (Uloric): Febuxostat is a hypouricemic drug and an alternative to allopurinol. Febuxostat inhibits the xanthine oxidase enzyme, blocks the production of uric acid and reduces the high serum uric acid level to normal levels. It is a thiazolecarboxylic acid derivative unlike allopurinol, which is a purine base analog. Febuxostat mainly targets the active site of xanthine oxidase enzyme, molybdenum-pterin channel, which is finally metabolized by glucuronidation and liver oxidation.


Benzodiazepines are muscle relaxant drugs and are used to reduce the neurologic symptoms of LNS. Commonly used Benzodiazepine drugs include alprazolam or diazepam, which lower the anxiety and severity of the neurologic manifestations including the extrapyramidal abnormalities. In addition, Behavioral problems can be effectively treated with the combination of adjunctive medications such as gabapentin and benzodiazepines.

Lorazepam (Ativan): Lorazepam belongs to the benzodiazepine class and acts as a sedative-hypnotic. It has a rapid onset of action and works by stimulating the gamma-aminobutyric acid (GABA) production, a neurotransmitter which depresses all parts of central nervous system (CNS), including the reticular formations and limbic system. Lorazepam is best advised to achieve more than 24 hours of sedation in high risk patients.

Diazepam (Diastat, Valium): Diazepam also stimulates the production GABA neurotransmitter which depresses all CNS including reticular formation and limbic system.


Anticonvulsant drugs reduce the severity of the LNS associated extrapyramidal manifestations. These drugs are usually prescribed as adjuvants in combination with other medications like benzodiazepines and gabapentin in case of attenuating behavioral problems.

Gabapentin (Neurontin): Gabapentin is an analogue of inhibitory GABA neurotransmitter and a membrane stabilizer. It acts mainly on the voltage driven calcium channels and auxiliary subunits of alpha (2) delta1 and alpha (2) delta2. Gabapentin drug is used for sedation purpose and to treat neuropathic pain.

Skeletal Muscle Relaxants

Skeletal muscle relaxants are used to reduce the severity of the neurologic manifestations of LNS. These drugs are used to reduce muscle pain; however, they should be used under physicians' guidance as they cause deep sedation and have highest addictive potential.

Baclofen (Gablofen, Lioresal): Baclofen is an anti-spasticity agent, which works by promoting the afferent terminal hyperpolarization and by suppressing the polysynaptic and monosynaptic reflexes at the spinal level.

Surgical intervention

Some patients may require gastrostomy due to dysphagia. Laser lithotripsy is often advised to extract kidney stones and to treat urogenital obstruction associated with nephrolithiasis.


What is the disease Prognosis?

The treatment outcome for Lesch-Nyhan disease is usually poor. Affected patients will be confined to a wheelchair and need assistance to walk and sit. The risk of developing LNS can be reduced by providing genetic counseling to the parents with LNS child.











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Dr Chaitra S's picture
Author: Dr Chaitra S

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