A metabolic disorder that occurs before birth and causes problems with the brain and behavior is called Lesch-Nyhan syndrome (LNS). It happens very rarely and before birth. People with this syndrome may also experience intellectual disability, poor muscle control, and severe arthritis. Typically, the primary symptom of Lesch-Nyhan syndrome is uncontrollable self-injury (such as head banging or finger or lip biting).
In people with LNS, there is a buildup of a natural waste product known as uric acid in the body. According to some research, this syndrome also affects dopamine levels. This is a chemical messenger that helps the brain function properly. Unfortunately, there is no way to cure this condition, and the outlook is poor. The only way to control this syndrome is early detection and prompt treatment.
Generally, it happens rarely and affects about 1 in 380,000 people. Most of the time, it affects boys. Furthermore, this syndrome was discovered in 1964.
Types of Lesch-Nyhan Syndrome
Usually, children with the classic form of this syndrome experience severe symptoms. However, those who develop other types of this condition tend to have milder symptoms. Furthermore, they may not injure themselves or develop movement issues. Check the types below:
- HPRT1-related neurologic function (HND)
- HPRT1-related hyperuricemia (Kelley-Seegmiller syndrome), which is one of the mildest types of LNS
What Are The Symptoms of Lesch-Nyhan Syndrome?
This condition causes multiple symptoms. While the most common signs of LNS are poor muscle control and developmental delays, it may also cause other symptoms. Sometimes, you may notice small orange-colored crystals in the baby’s diaper. It indicates an increased uric acid level in the blood. Check for other symptoms of LNS below:
Injuring Themselves and Others
Uncontrollable self-injury is one of the most common symptoms of LNS. The behavior often involves banging the head or limbs, biting lips, fingers, or cheeks, and poking the eyes. In rare cases, the babies may try to hurt other people.
Muscle and Movement Issues
These include:
- Opisthotonos (arched back caused by muscle spasms)
- Dysphagia (swallowing problems)
- Hyperreflexia
- Dystonia (involuntary muscle movements)
- Choreoathetosis (involuntary wiggling, writhing, or twitching)
- Ballismus (repetitive movement of the legs or arms)
- Problems with walking and feeding with hands
- Chorea (jerking movements)
- Spasticity (muscle stiffness)
- Dysarthria (slow or slurred speech)
Learning Problems
In some cases, children with LNS may experience learning disabilities, mental problems (including poor memory and short attention span), and difficulty making complex plans.
Diseases
Those who develop LNS may also experience the following health conditions. They are often caused by the buildup of uric acid in the body. Check some examples below:
- Gout
- Kidney stones or failure
- Recurrent vomiting
- Megaloblastic anemia (which is often caused by a deficiency of vitamin B12)
- Bladder stones
If you notice your child has any of the symptoms listed above, immediately contact your healthcare professional. Otherwise, it may lead to serious complications.
Causes
This condition occurs due to a mutation (change) in the HPRT1 gene. It is responsible for producing an important enzyme called HPRT that helps the body function properly by speeding up chemical reactions in the body (metabolism). However, in children with LNS, the body cannot process chemicals (purines) properly. As a result, these chemicals turn into uric acid, which is a waste product found in the blood.
Most of the time, uric acid passes through the kidneys in the urine and leaves the body. In people with LNS, this acid begins to build up in the body (hyperuricemia). Therefore, the acid clumps into small stones or crystals in the hands, feet, and skin. They can cause inflammation and certain health conditions (such as gout). In addition, people with LNS may also experience kidney or bladder stones that block the urine and cause pain. If you develop a severe form of LNS, the kidneys may not work properly, leading to renal failure.
While LNS is an inherited metabolic disorder that is often passed from biological mothers to their biological sons. In any case, there are people with LNS who do not have a family history of the disease. In this case, children develop a mutation in the HPRT1 gene spontaneously.
Are There Other Conditions Similar to Lesch-Nyhan Syndrome?
In general, there are multiple diseases that cause symptoms similar to LNS. That’s why it is important to get an accurate diagnosis. Check some examples below:
- Cerebral palsy
- Autism spectrum disorder
- Familial dysautonomia
- Fragile X syndrome
- Cornelia de Lange syndrome
- Hereditary sensory neuropathy
- Huntington’s disease
- Phosphoribosyl pyrophosphate (PRPP) synthetase hyperactivity
- Rett syndrome
- Tourette syndrome
- G6PD (glucose 6-phosphate dehydrogenase) deficiency
How to Prevent Lesch-Nyhan Syndrome?
Unfortunately, there is no way to prevent this condition because it occurs during pregnancy. Sometimes, performing genetic tests before pregnancy may help identify the abnormal gene that causes this syndrome. It is very important to understand the risks of having children with LNS.
Diagnosis
Like the diagnosis of other health conditions, the LNS diagnosis begins with a physical examination in which doctors will try to find signs associated with LNS. They may also ask some questions about the symptoms and family history to gather more information about your disease. However, they may also perform some tests that may help confirm or rule out LNS. For example:
- Blood tests
- Genetic tests
In some cases, LNS can be diagnosed before birth. Usually, doctors perform amniocentesis or chorionic villus sampling.
Treatment
Commonly, children with LNS need a healthcare team to manage their condition. It often includes neurologists, nephrologists, geneticists, occupational and physical therapists, pediatricians, social workers, speech-language pathologists, and urologists. There is no way to cure this condition. That’s why the treatment goal is to relieve the symptoms, prevent life-threatening complications, and improve your child’s quality of life. Check below some treatment options often recommended by doctors for people with LNS:
- Medicines to treat high levels of uric acid
- Feeding and swallowing support
- Physical and occupational therapy
- Supportive equipment (including a wheelchair)
- Certain procedures to break up kidney or bladder stones (such as shockwave or laser lithotripsy)
- Protective devices, such as a splint or mouthguard, to prevent involuntary movements
Frequently Asked Questions
When should I seek care for my child?
Typically, it is recommended to visit a doctor if you notice your child has symptoms that resemble LNS. Early detection and prompt treatment are very important.
What is the outlook for Lesch-Nyhan syndrome?
Generally, the prognosis for children with LNS is poor. Frequently, they cannot walk and need a wheelchair, and most of them have a shortened lifespan. In rare cases, children with LNS can live more than 20 years.
Are there other names for Lesch-Nyhan syndrome?
Yes, this condition has multiple names. Check some of them below:
- X-linked hyperuricemia
- Primary hyperuricemia syndrome
- Total HPRT deficiency
- Lesch-Nyhan disease (LND)
- Kelley-Seegmiller syndrome
- Juvenile hyperuricemia syndrome or juvenile gout
- Complete hypoxanthine-guanine phosphoribosyltransferase deficiency
- Choreoathetosis self-mutilation syndrome and others
Can Lesch-Nyhan syndrome affect girls?
Yes, but it is extremely rare. Because Lesch-Nyhan syndrome is an X-linked genetic disorder, it primarily affects boys. Girls usually have one healthy copy of the HPRT1 gene that protects them from developing the classic form of the disease. However, in rare cases, females can develop symptoms due to unusual genetic changes or abnormalities involving the X chromosome.
At what age do symptoms of Lesch-Nyhan syndrome usually appear?
Most infants appear healthy at birth. The first signs often develop between 3 and 6 months of age, when developmental delays, poor muscle control, and low muscle tone become noticeable. Self-injurious behaviors typically begin after the first year of life, often when teeth erupt.
Does every child with Lesch-Nyhan syndrome develop self-injury?
No. While self-injurious behavior is a hallmark of the classic form of Lesch-Nyhan syndrome, children with milder HPRT1-related disorders may never develop this symptom. The severity of symptoms depends largely on how much HPRT enzyme activity remains.
Can people with Lesch-Nyhan syndrome attend school?
Many children with Lesch-Nyhan syndrome can attend school with appropriate accommodations. They often benefit from individualized education programs (IEPs), physical and occupational therapy, speech therapy, and assistive communication devices. The level of support needed depends on the severity of their physical and cognitive impairments.
How is high uric acid managed in people with Lesch-Nyhan syndrome?
Doctors commonly prescribe medications that lower uric acid levels, such as Allopurinol, to help prevent kidney stones and gout. In addition, drinking plenty of fluids and having regular follow-up appointments can help reduce complications caused by excess uric acid.
Is genetic counseling recommended for families affected by Lesch-Nyhan syndrome?
Yes. Genetic counseling is strongly recommended for families with a history of Lesch-Nyhan syndrome. A genetic counselor can explain inheritance patterns, discuss the likelihood of future children being affected, and review available carrier testing and prenatal testing options.
Can adults live with Lesch-Nyhan syndrome?
Yes. Although Lesch-Nyhan syndrome is associated with a shortened life expectancy, advances in supportive care have allowed some people to survive into adulthood. Ongoing medical care, nutritional support, prevention of kidney complications, and management of neurological symptoms can improve both longevity and quality of life. Ask your healthcare provider if you have any other questions.
