Lesch-nyhan syndrome

Boys with Lesch-Nyhan syndrome have significant problems controlling their muscles. For this reason, almost all children with Lesch-Nyhan syndrome never learn to walk.

The best person to discuss the symptoms of Lesch-Nyhan syndrome is a specialist in medical genetics (a specialist in inherited/genetic conditions) or pediatric neurology (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologiest in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

Genetic testing can be offered for other family members if a HPRT1 gene change is identified in an affected person. Testing can be offered to other people depending on who is diagnosed first and the carrier status of the mother. A few examples are the following:

Urinary differences that can be seen in Lesch-Nyhan syndrome occur because of the build up on uric acid in the body. The extra uric acid can form into crystals and stones. These crystals may be seen as "orange-colored sand" deposits in the diapers. A stone may become caught in the kidneys and cause blood in the urine (hematuria). The stones can lead to urinary tract infections, bladder stones-if it travels to the bladder, and can cause more serious kidney problems if not treated. Management includes drinking plenty of fluids (staying hydrated) and treatment with the medication allopurinol. With proper management, the complications can be greatly reduced.

A pediatric urologist (a doctor specializing in problems with the kidneys and urinary tract) can help manage these complications. To find a pediatric urologist, ask your doctor for a recommendation.

If a female has the possibility to be a carrier of Lesch-Nyhan syndrome, testing is available.

HPRT (hypoxanthine phosphoribosyltransferase) enzyme analysis is not widely used to see if a female is a carrier of Lesch-Nyhan syndrome because there is a chance for false positives and false negatives. However, testing can be done to measure the frequency of HPRT-deficient white blood cells in their growth medium.

Genetic testing is also available to see if a female is a carrier of Lesch-Nyhan syndrome. For genetic testing, the HPRT1 gene is analyzed usually using a blood sample. It is most useful to perform carrier testing when the specific change or gene mutation in the HPRT1 gene is known in the family. This is usually found by first performing genetic testing on the person who has Lesch-Nyhan syndrome.

To learn more about testing for Lesch-Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

It is extremely rare for females to be diagnosed with Lesch Nyhan syndrome or Lesch Nyhan variant. Most females with a mutation in HPRT1, the gene associated with Lesch Nyhan, are carriers of the disease and do not have any symptoms; but there have been reports, less than 10 currently, of females with the condition. Of the cases that have been reported, most of the females were diagnosed with the most severe end of the syndrome, Lesch Nyhan syndrome. Most of the girls presented with developmental delay and later were found to have hyperuricemia, intellectual disability, severe dystonia, and self-injurious behavior, which are symptoms typical of a male with the condition. There is one report of a female who presented with acute renal failure at 2 months of age, and was later diagnosed with Lesch Nyhan syndrome. There is also one report of a female with the hyperuricemic (HRH) variant, in which patients have hyperuricemia without any neurological or behavioral abnormalities, who presented with gout.

In all of these cases, it was discovered that there was non-random X-inactivation in each of the females. Typically, females each have 2 X chromosomes, though one X chromosome in every cell is inactivated or "turned off". In most females, the X that is inactivated is random, and occurs very early in development. This was found to be the case in all females with Lesch Nyhan syndrome; the X with the HPRT1 mutation was the X that was active.

Greater than 90-95% of males with Lesch-Nyhan syndrome are found to have a change (mutation) in the HPRT1 gene located on the X chromosome. A person can still have Lesch-Nyhan syndrome even if a gene change is not found on genetic testing.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Neurological differences that can be seen in Lesch-Nyhan syndrome are usually noticeable before 12 months of age. These include uncontrollable movements in the arms and legs (dystonia), repetitive movements (chorea) such as raising and lowering of the shoulders, and/or facial grimacing, and low muscle tone or soft muscles (hypotonia). Later there is increased muscle tone and muscle rigidity (spasticity). These neurological differences may resemble cerebral palsy.

Developmental delays are also evident within the first year of life with many affected boys delayed in reaching, or failing to reach, developmental milestones such as sitting and crawling. Most will not learn to walk.

The best person to diagnose Lesch-Nyhan syndrome and discuss the symptoms is a specialist in medical genetics (a specialist in inherited/genetic conditions) or pediatric neurology (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologiest in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

The usual abbreviation for Lesch-Nyhan syndrome is LNS.

To learn if there is another name or abbreviation for Lesch Nyhan syndrome a doctor might use, ask them if they are using another term for Lesch Nyhan syndrome or look on a reliable website such Genetics Home Reference.

Lesch-Nyhan syndrome is a condition that causes neurological problems that resemble cerebral palsy and characteristic behavioral issues. It almost always occurs in boys and is due to a build up of uric acid in the body. Uric acid is a waste product of normal chemical processes of the body and is found in blood and urine.

Neurological differences in Lesch-Nyhan syndrome are usually noticeable before 12 months of age. These include uncontrollable movements in the arms and legs (dystonia), repetitive movements (chorea), and low muscle tone or soft muscles (hypotonia). Later there is increased muscle tone and muscle rigidity (spasticity). These neurological differences may resemble cerebral palsy. Many affected boys are delayed in reaching, or fail to reach, developmental milestones such as sitting and crawling. Most will not learn to walk.

People with Lesch-Nyhan syndrome often try to injure themselves through biting, banging of their heads, arms, and legs, and scratching. The biting behaviors are severe and often lead to loss of tissue.

The extra uric acid sometimes forms crystals in the kidneys causing kidney stones. These can also lead to other problems in the urinary tract and kidneys if not treated. Crystals formed from the uric acid may also be found in the joints. This can cause stiffness and swelling in the joints (gouty arthritis).

The best person to diagnose Lesch-Nyhan syndrome and discuss the symptoms is a medical geneticist (a specialist in inherited/genetic conditions) or pediatric neurologist (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologist in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

Harmful changes (mutations) in the HPRT1 gene are known to cause Lesch-Nyhan Syndrome. The HPRT1 gene is named after the protein that it gives the instructions to make, the enzyme “hypoxanthine-guanine phosphoribosyltransferase" or HPRT for short. The gene is located on the X chromosome (one of the sex chromosomes; the other sex chromosome is the Y chromosome). The exact location of the HPRT1 gene is chromosome Xq26.1.

To learn more about the genetics of Lesch-Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

When a person inherits a “variant” in the HPRT1 gene for Lesch-Nyhan syndrome, it means they have a change in the gene, but it is currently not known if this change actually causes Lesch-Nyhan syndrome. These are often called variants of uncertain significance (VUS). Sometimes the interpretation of variants change as more people are tested and more data is received by the laboratory. Your genetics doctor can also help to decide whether or not they think the variant of uncertain significance is significant for you or not.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Genotype refers to the specific change in a gene. Phenotype is the outward traits that are observed. Genotype-phenotype correlation means that a specific change in the gene causes specific traits or medical concerns. HPRT1 gene mutations that completely disrupt HPRT (hypoxanthine-guanine phosphoribosyltransferase) enzyme function, meaning that very little or no ezyme is made, are associated with Lesch-Nyhan syndrome. HPRT1 gene mutations that do not completely disrupt HPRT enzyme function and allow the enzyme to function at higher levels cause HPRT-related hyperuricemia and HPRT-related gout.

HPRT-related hyperuricemia may cause pain and swelling in joints (gout), crystals in the urine (this can be seen on urine test), and kidney stones. Sometimes renal disease may occur. Males affected with this condition usually show symptoms in childhood. Female carriers may develop features of this condition later in life. People with this condition do not have the neurological or behavioral problems of those with Lesch-Nyhan syndrome.

HPRT-related gout (also known as Kelley-Seegmiller syndrome) explains less than 2% of adult males with gout.

It will be important to ask your geneticist and genetic counselor if there are any reports of genotype-phenotype correlation if a HPRT1 gene mutation is found. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

The most significant behavioral differences that can be seen in Lesch-Nyhan syndrome are the self-injuring behaviors. A child may repeatedly bite their lips, cheeks, fingers, and hands. These behaviors may lead to loss of tissue. They may also hit their head, arms, and legs against hard objects. Some children may scratch their face repeatedly. However, they can still feel pain. It is often necessary to restrain boys with Lesch-Nyhan syndrome when these behaviors appear, or they may cause serious injuries. In many cases, being restrained is comforting to the boys because they know that they will not hurt themselves. This is sometimes treated by removing teeth and behavioral therapy. Some medications have also shown benefit in some people.

These behaviors often begin between the ages of 2-3, but may occur in the first year of life, or may begin much later.

Other behavior may include aggressiveness, spitting, foul language, and vomiting.

The best person to diagnose Lesch-Nyhan syndrome and discuss the symptoms is a specialist in medical genetics (a specialist in inherited/genetic conditions) or pediatric neurology (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologiest in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

Lesch-Nyhan syndrome is a condition that causes neurological problems that resemble cerebral palsy and characteristic behavioral issues. It almost always occurs in boys and is due to a build up of uric acid in the body. Uric acid is a waste product of normal chemical processes of the body and is found in blood and urine.

Symptoms of Lesch-Nyhan syndrome may be seen as early as six months of age. Early signs of Lesch-Nyhan syndrome include orange-colored deposits (“orange sand”) in the diapers of infants. These are crystals formed from the extra uric acid. Sometimes kidney stones develop and can cause blood in the urine (hematuria) and increase the chance of urinary tract infections. If untreated, the kidney stones can lead to very serious kidney problems. The excess uric acid is treated with a medication called allopurinol. Crystals formed from the uric acid may also be found in the joints. This can cause pain and swelling in the joints (gout). However, this does not usually occur until the teenage or adult years and can be treated with the same medication.

Neurological differences in Lesch-Nyhan syndrome are usually noticeable before 12 months of age. These include uncontrollable movements in the arms and legs (dystonia), repetitive movements (chorea) such as raising and lowering of the shoulders, and/or facial grimacing, and low muscle tone or soft muscles (hypotonia). The low muscle tone may make it difficult for them to hold up their head in infancy. Later there is increased muscle tone and muscle rigidity (spasticity). These neurological differences may resemble cerebral palsy.

Developmental delays are also evident within the first year of life. Many affected boys are delayed in reaching, or fail to reach, developmental milestones such as sitting and crawling. Most will not learn to walk. Intelligence is usually moderately affected although it is difficult to assess because many boys cannot speak well, have difficulty with movement, and behavior problems

The most significant behavioral differences that can be seen in about 85% of boys with Lesch-Nyhan syndrome are the self-injuring behaviors. A child may repeatedly bite their lips, cheeks, fingers, and hands. These behaviors may lead to loss of tissue. They may also hit their head, arms, and legs against hard objects. Some children may scratch their face repeatedly. However, they still feel pain. It is often necessary to restrain boys with Lesch-Nyhan syndrome when these behaviors appear, or they may cause serious injuries. In many cases, being restrained is comforting to the boys because they know that they will not hurt themselves. These behaviors often begin between the ages of 2-3, but may occur in the first year of life, or may begin much later. Other behaviors may include aggressiveness, spitting, foul language, and vomiting.

Other health concerns that can be seen in Lesch-Nyhan syndrome include trouble swallowing and feeding difficulties due to recurrent vomiting. This is sometimes severe enough to impair nutrition and growth and they may be underweight for their age. If it is severe, a feeding tube may have to be inserted into the stomach. Another issue is anemia with very large red cells in the blood (megaloblastic anemia). Fortunately, this does not usually cause problems or require treatment. Some experience severe muscle spasms, scoliosis, hip dislocations, and fixation of joints in a flexed position (contractures). Not all people with Lesch-Nyhan Syndrome have these features.

With proper management, boys with Lesch-Nyhan syndrome can live into their teens and twenties.

The best person to discuss the symptoms of Lesch-Nyhan syndrome is a medical geneticist (a specialist in inherited/genetic conditions) or pediatric neurologist (a specialist in conditions of the nervous system for children). Pediatric urologist (kidney and urinary tract specialists) should also be consulted. Medical geneticists and pediatric neurologist in an area can be found by talking to doctors about who they would recommend or to find a genetics clinic use the “Find Genetic Services” function at the American College of Medical Genetics.

When a boy has been diagnosed with Lesch-Nyhan syndrome the following evaluations are recommended to establish a treatment and management plan:

Early signs of Lesch-Nyhan syndrome include orange-colored deposits (“orange sand”) in the diapers of infants, uncontrollable movements, low muscle tone (hypotonia), and developmental delay. The orange-colored deposits are due to high levels of uric acid in the urine. Uncontrollable movements can be seen before the age of 12 months, in addition to delayed developmental milestones such as sitting or crawling. Another early sign in the first few years may include self-injuring behaviors (biting themselves, scratching themselves, hitting their head, arms, and legs against objects).

The best person to diagnose Lesch-Nyhan syndrome and discuss the symptoms is a specialist in medical genetics (a specialist in inherited/genetic conditions) or pediatric neurology (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologiest in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

Other health concerns that can be seen in Lesch-Nyhan syndrome include trouble swallowing and feeding difficulties due to recurrent vomiting. This is sometimes severe enough to impair nutrition and growth and they may be underweight for their age. If it is severe, a feeding tube may have to be inserted into the stomach. Another issue is anemia with very large red cells in the blood (megaloblastic anemia). Fortunately, this does not usually cause problems or require treatment. Some experience severe muscle spasms, scoliosis, hip dislocations, and fixation of joints in a flexed position (contractures). Not all people with Lesch-Nyhan syndrome have these features.

The best person to discuss the symptoms of Lesch-Nyhan syndrome is a medical geneticist (a specialist in inherited/genetic conditions) or pediatric neurologist (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologist in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

People with Lesch-Nyhan syndrome have symptoms that affect many different systems of the body. They should seek advice and medical care from a team of specialists that may include:

The treatment for Lesch-Nyhan syndrome is individualized and is focused on the following three areas:

There is a "hallmark" feature of Lesch-Nyhan syndrome. In about 85% of affected males, self-injury/self-mutilation occurs. This behavior usually begins between 2-3 years of age, but can also occur earlier or later. A child may repeatedly bite their lips, cheeks, fingers, and hands. These behaviors may lead to loss of tissue. They may also hit their head, arms, and legs against hard objects. Some children may scratch their face repeatedly. It is often necessary to restrain boys with Lesch-Nyhan syndrome when these biting behaviors appear, or they may cause serious injuries. In many cases, being restrained is comforting to the boys because they know that they will not hurt themselves.

The best person to discuss the symptoms of Lesch-Nyhan syndrome is a specialist in medical genetics (a specialist in inherited/genetic conditions) or pediatric neurology (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologist in an area can be found by talking to doctors about who they would recommend or using the "Find Genetic Services" function at the American College of Medical Genetics.

Each state has a newborn screen which includes a group of genetic conditions. Lesch-Nyhan syndrome is not included in any newborn screens in the United States. If there is a family history of Lesch-Nyhan syndrome or if Lesch-Nyhan syndrome is suspected in a child, genetic testing can be performed using cord blood or another blood sample.

A geneticist or genetic counselor can help explain information about testing for Lesch-Nyhan syndrome. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Testing for Lesch-Nyhan syndrome includes both HPRT (hypoxanthine-guanine phosphoribosyltransferase) enzyme activity test and genetic testing. Sometimes an initial screen to check the uric acid levels in the blood or urine is performed. If there is uric acid overproduction (hyperuricemia), this is a feature of Lesch-Nyhan syndrome and increases the likelihood that Lesch-Nyhan syndrome is a possibility. This test is not diagnostic (it can’t give a yes or no answer about if a person has LNS) and further testing will likely be needed.

For enzyme testing, the HPRT enzyme activity assessed. If this enzyme activity is less than 1.5% of the normal levels in cells from any tissue (blood, skin cells), a male receives a diagnosis of Lesch-Nyhan syndrome.

As of January 11, 2016, there is only one gene, HPRT1, currently known to be associated with Lesch-Nyhan syndrome. Genetic testing involves analyzing this gene for changes. There are two main types of analyses; these are called sequencing and deletion/duplication. You can imagine the HPRT1 gene as a long sentence that provides instruction to the body. Sequencing looks for spelling errors in this sentence. Deletion/duplication involves looking for extra or missing words in this sentence. Spelling errors and extra/missing words can cause the sentence to no longer make sense and therefore no longer provide the proper instruction for the body, causing Lesch-Nyhan syndrome. Some labs in the United States offer both sequencing and deletion/duplication of the HPRT1 gene. Some labs in the United States just offer sequencing or deletion/duplication of the HPRT1 gene. Some labs look only for the specific spelling error when a HPRT1 gene mutation is known in the family.

A geneticist or genetic counselor can help a person get tested and interpret the results. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

There is no cure for Lesch-Nyhan Syndrome. Treatment is limited to management and surveillance of medical concerns in the following areas:
1. Overproduction of uric acid. One can control the increased production of uric acid by taking allopurinol. Allopurinol slows down the production of uric acid. It is also important to drink lots of fluids to stay hydrated; this helps the uric acid be better eliminated in the urine. This helps prevent kidney and bladder stones from forming. If stones do form, they can usually be broken up or removed. Certain medications called uricosuric drugs, like probenecid, should also be avoided.
2. Neurological concerns. For spasticity, medications such as baclofen and benzodiazepines can be taken. Having a comfortable wheelchair is also important.
3. Behavior concerns. Medication may be taken for behavioral concerns but there is no current effective intervention. Promising medications include gabapentin, carbamazepine, diazepam, others. Physical restraint is often needed. Sharp and dangerous objects should not be in arm’s reach. Some people get their teeth removed if they can’t control biting themselves. Behavioral therapy is also important.

Treatment should be discussed with a team of specialists which may include a medical geneticist, pediatric neurologist or pediatric nephrologist (kidney specialist), in addition to a specialist in behavioral therapy. These specialists can be found by talking to doctors about who they would recommend. A genetics clinic can be located using the “Find Genetic Services” function at the American College of Medical Genetics.

The life expectancy for males with Lesch-Nyhan syndrome is reduced. With proper management, most males survive into their teens or 20’s.

If a male is affected with Lesch-Nyhan Syndrome, he should avoid Probenecid and other uricosuric drugs because they may cause the kidneys to fail to produce urine because of the formation of uric acid crystals. One should also avoid dehydration.

A pediatric urologist (a doctor specializing in problems with the kidneys and urinary tract) can help manage these complications. To find a pediatric urologist, ask your doctor for a recommendation.

Most males with the same HPRT1 gene mutation causing Lesch-Nyhan syndrome have similar medical concerns and clinical features, but there have been a few exceptions seen before.

To learn more about the genetics of Lesch-Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

If a HPRT1 gene mutation cannot be identified in the family, testing for Lesch-Nyhan syndrome during the pregnancy is still available. The first step is to determine if the baby is male or female. Chorionic villus sampling (CVS) and amniocentesis are both available. CVS involves removing a small sample of the placenta and sending it to a laboratory for genetic testing. CVS can be performed around 10-12 weeks of gestation. Amniocentesis involves taking a sample of amniotic fluid and sending it to the laboratory for genetic testing. This testing can be performed starting at 15 weeks of gestation. Each test has a small risk for miscarriage. If the baby is male, further testing can be performed on the cells. If a HPRT1 gene mutation is not known in the family, a test to check the levels of the HPRT enzyme can be performed. If one is interested in this prenatal diagnostic testing, they can speak with a reproductive genetic counselor in their area. Genetic counselors can be found using the website for the National Society of Genetic Counselors under "Find a Counselor".

To learn more about testing for Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

If someone has Lesch-Nyhan syndrome, their primary care provider should know the management and surveillance guidelines. A complete blood count will be needed to evaluate for megaloblastic anemia. Supportive services (speech therapy, physical therapy, occupational therapy) need to be started early on. The primary care provider should look for early signs of self-injury and monitor uric acid levels. They should also look for signs of kidney stones. Continued follow up with a neurologist, developmental specialist, and nephrologist/urologist will be needed.

The best person to discuss the symptoms of Lesch-Nyhan syndrome is a medical geneticist (a specialist in inherited/genetic conditions) or pediatric neurologist (a specialist in conditions of the nervous system for children). Pediatric urologist (kidney and urinary tract specialists) should also be consulted. Medical geneticists and pediatric neurologist in an area can be found by talking to doctors about who they would recommend or to find a genetics clinic use the “Find Genetic Services” function at the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Lesch-Nyhan syndrome (LNS) is inherited in an X-linked recessive pattern. The “X” chromosome is a sex chromosome. The “Y” chromosome is the other sex chromosome. Males usually have one X chromosome and one Y chromosome. Females usually have two X chromosomes. The HPRT1 gene for Lesch-Nyhan Syndrome is located on the X chromosome. When a female has a change (mutation) in one of her two HPRT1 genes, she is called a carrier for LNS.

If a woman is a carrier of Lesch-Nyhan syndrome (LNS), there is 50% chance that each male child will have LNS, and a 50% chance of a male child NOT having LNS. For a female child of a carrier, there is a 50% chance that she will be a carrier of Lesch-Nyhan syndrome.

Overall, in each pregnancy there is a 25% chance to have a boy with LNS, 25% chance to have a boy who does not have LNS, 25% chance to have a girl who is a carrier, 25% chance to have a girl who is not a carrier.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

If a mother is a carrier of Lesch-Nyhan syndrome and the gene change in the family is known, testing can be performed during the pregnancy. The first step is to see if the baby is male or female, then the specific gene can be looked at for the change that is in the family. If the gene change is not known, enzyme testing may be possible.

Chorionic villus sampling (CVS) and amniocentesis two options for prenatal screening for Lesch-Nyhan syndrome. CVS involves removing a small sample of the placenta and sending it to a laboratory for genetic testing. CVS can be performed around 10-12 weeks of gestation. Amniocentesis involves taking a sample of amniotic fluid and sending it to the laboratory for genetic testing. This testing can be performed starting at 15 weeks of gestation. Each of these procedures has a small risk for miscarriage. If the baby is found to be male, further testing can be performed on the cells. If the mother knows what specific HPRT1 gene mutation she is a carrier of, this HPRT1 gene mutation can be looked for specifically. If a HPRT1 gene mutation is not known in the family, a HPRT enzyme test to check the levels can be performed.

Pre-implantation genetic diagnosis, where an embryo that is being used for in vitro fertilization is tested for gender and/or the genetic change, could also be performed when there is a known mutation in the family.

If one is interested in this prenatal testing, they can speak with a reproductive genetic counselor in their area. Genetic counselors can be found using the website for the National Society of Genetic Counselors under "Find a Counselor".

To learn more about testing for Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

It is a personal decision whether or not to pursue genetic testing during a pregnancy. Even if a mother is not found to be a carrier of the same HPRT1 gene mutation previously found in her child, there is still the small possibility of germline mosaicism. Germline mosaicism is where only some of the egg cells have the HPRT1 gene mutation; this is unable to be detected through a blood draw which is usually how mothers are tested to see if they are carriers. The recurrence risk for future pregnancies is low, likely less than 1%, but prenatal genetic testing can still be pursued if parents desire. If parents are interested, they can speak with a prenatal/reproductive genetic counselor. Genetic counselors can be found using the website for the National Society of Genetic Counselors under "Find a Counselor".

Most males with Lesch-Nyhan syndrome cannot have children. If a male is affected with Lesch-Nyhan syndrome, his ability to have children will depend on the severity of his condition.

Lesch-Nyhan syndrome is inherited in an X-linked recessive pattern. The “X” chromosome is a sex chromosome. The “Y” chromosome is the other sex chromosome. Males usually have one X chromosome and one Y chromosome. Females usually have two X chromosomes. The HPRT1 gene for Lesch-Nyhan Syndrome is located on the X chromosome.

If a male is mildly affected and decides to have children, there is a 0% chance that his male children will be affected (because males pass on their Y sex chromosome to their male children), and a 100% chance that his female children will be carriers (because males pass on their X chromosome to their female children).

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

A change in the HPRT1 gene causing Lesch-Nyhan syndrome can be inherited from a "carrier" mother or it can occur for the first time in the child (de novo mutation). When a boy has a HPRT1 gene mutation, it is predicted that about 2/3 (66%) of the time the mother will be a carrier, and 1/3 (33%) of the time the HPRT1 gene mutation happens for the first time in the child and is not inherited from the mother (de novo). Some studies show that there may be a higher chance than 2/3 (66%) for the mother to be carrier in Lesch-Nyhan syndrome.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

A change in the HPRT1 gene causing Lesch-Nyhan syndrome can be inherited from a "carrier" mother or it can occur for the first time in the child (de novo mutation). When a boy has a HPRT1 gene mutation, it is predicted that about 2/3 (66%) of the time the mother will be a carrier, and 1/3 (33%) of the time the HPRT1 gene mutation happens for the first time in the child and is not inherited from the mother (de novo). Some studies show that there may be a higher chance than 2/3 (66%) for the mother to be carrier in Lesch-Nyhan syndrome.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

As of January 11, 2016, there are over ten different laboratories in the United States that perform testing for Lesch-Nyhan Syndrome. Two laboratories offer HPRT (hypoxanthine-guanine phosphoribosyltransferase) enzyme activity test. Over ten labs offer genetic testing which involves HPRT1 gene analysis.

Testing is typically ordered by a geneticist and genetic counselor. Two great websites that list the different labs are the following:

Lesch-Nyhan syndrome is inherited in an X-linked recessive pattern. The “X” chromosome is a sex chromosome. The “Y” chromosome is the other sex chromosome. Males usually have one X chromosome and one Y chromosome. Females usually have two X chromosomes. The HPRT1 gene for Lesch-Nyhan Syndrome is located on the X chromosome. Because males only have one X chromosome, and therefore one HPRT1 gene, if this gene has a change (mutation) causing the gene to not work correctly, the male is affected with Lesch-Nyhan syndrome. Because females have two X chromosomes, if one of their HPRT1 genes has a change (mutation) and the other does not have a change, they are known as “carriers.” Most female carriers have no symptoms of Lesch-Nyhan syndrome. There have been a few very rare reports of females who have severe symptoms of Lesch-Nyhan syndrome.

A change in the HPRT1 gene can be inherited from a "carrier" mother or it can occur for the first time in the child (de novo mutation). When a male child has a HPRT1 gene mutation, it is predicted that about 2/3 (66%) of the time the mother is found to be a carrier and 1/3 (33%) of the time the HPRT1 gene mutation happens brand new in the child and is not inherited from the mother (de novo). There is some suspicion for a higher chance than 2/3 (66%) for the mother to be carrier in Lesch-Nyhan syndrome.

The chance of having another child with Lesch-Nyhan syndrome will depend on whether the mother is a carrier or not. If the mother is not a carrier, the chance of having another child with Lesch-Nyhan syndrome is small although not impossible due to the chance that more than one of her eggs may contain the gene change (germline mosaicism).

If a female is a carrier of Lesch-Nyhan syndrome (LNS), there is 50% chance that each male child will have Lesch-Nyhan syndrome, and a 50% chance of a male child NOT having Lesch-Nyhan syndrome. For a female child of a carrier there is a 50% chance that she will be a carrier of Lesch-Nyhan syndrome. Overall, in each pregnancy there is a 25% chance to have a boy with LNS, 25% chance to have a boy who does not have LNS, 25% chance to have a girl who is a carrier, 25% chance to have a girl who is not a carrier.

Genetic testing of the HPRT1 gene is available.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Lesch-Nyhan syndrome is caused when there is a change in the HPRT1 gene on the X chromosome. The protein produced from the HPRT1 gene is an enzyme called hypoxanthine-guanine phosphoribosyltransferase (HPRT). This protein helps the cells in our body recycle something called purines. Purines are building blocks of DNA and RNA (these carry our genetic information) and these need to be recycled in order to produce DNA. Purines are found in many foods such as meats and legumes. When there is a mutation in the HPRT1 gene, the HPRT enzyme either does not work properly, works at very low levels, or does not work at all. Because of this, a waste product of purine breakdown called uric acid builds up in the body. This buildup of uric acid can cause “gouty” arthritis, kidney stones, and bladder stones. Researchers are currently not sure how this causes the neurological and behavior features of Lesch-Nyhan syndrome.

To learn more about the genetics of Lesch-Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

If a male is suspected to be affected with Lesch-Nyhan syndrome (LNS), enzyme testing and genetic testing are both available. Sometimes an initial screen to check the uric acid levels in the blood or urine is performed. If there is uric acid overproduction (hyperuricemia), this is a feature of Lesch-Nyhan syndrome and increases the likelihood that Lesch-Nyhan syndrome is a possibility. This test is not diagnostic (it can’t give a yes or no answer about if a person has LNS) and further testing will likely be needed.

For enzyme testing, the HPRT (hypoxanthine-guanine phosphoribosyltransferase) enzyme activity is looked at. If this enzyme activity is less than 1.5% of the normal levels in cells from any tissue (blood, skin cells), a male receives a diagnosis of Lesch-Nyhan syndrome.

For genetic testing, the HPRT1 gene is analyzed to see if there are any changes (mutations) in the gene. This testing is usually done on a blood sample. There are two main types of analyses; these are called sequencing and deletion/duplication. You can imagine the HPRT1 gene as a long sentence that provides instruction to the body. Sequencing looks for spelling errors in this sentence. Deletion/duplication involves looking for extra or missing words in this sentence. Spelling errors and extra/missing words can cause the sentence to no longer make sense and therefore no longer provide the proper instruction for the body, causing Lesch-Nyhan syndrome. Some labs in the United States offer both sequencing and deletion/duplication of the HPRT1 gene. Some labs in the United States just offer either sequencing or deletion/duplication of the HPRT1 gene. Some labs also look for the particular spelling error identified when an HPRT1 gene mutation is known in the family.

Enzyme analysis and genetic testing for Lesch-Nyhan syndrome are typically ordered by a geneticist and genetic counselor after seeing them for an appointment. A clinic appointment typically involves a complete review of the patient’s medical history, a three generation family history that documents health problems and genetic conditions, a detailed physical examination, discussion of recommended testing, and consent for genetic testing if the patient/guardian is interested. Sometimes this happens in one clinic visit, and sometimes this happens over the span of a few clinic visits. Each clinic is different. In terms of insurance, sometimes the clinic checks with your insurance, and sometimes it is your responsibility to call your insurance. As stated earlier, each clinic operates differently. If enzyme analysis or genetic testing are pursued, a blood sample and signed paperwork is sent to a laboratory that performs the testing. Results are then sent back to the geneticist and genetic counselor who contact the patient/guardian with results.

To learn more about testing for Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

If a male is suspected to be affected with Lesch-Nyhan syndrome (LNS), both enzyme testing and genetic testing are available. Sometimes and initial screen to check the uric acid levels in the blood or urine. If there is uric acid overproduction (hyperuricemia), this is a feature of Lesch-Nyhan syndrome and increases the likelihood that Lesch-Nyhan syndrome is a possibility. This test is not diagnostic (it can’t give a yes or no answer about if a person has LNS) and further testing will likely be needed.

For enzyme testing, the HPRT (hypoxanthine phosphoribosyltransferase) enzyme activity assessed. If this enzyme activity is less than 1.5% of the normal levels in cells from any tissue (blood, skin cells), a male receives a diagnosis of Lesch-Nyhan syndrome.

For genetic testing, the HPRT1 gene is analyzed to see if there are any changes (mutations) in the gene. This testing is usually done on a blood sample. There are two main types of analyses; these are called sequencing and deletion/duplication. You can imagine the HPRT1 gene as a long sentence that provides instruction to the body. Sequencing looks for spelling errors in this sentence. Deletion/duplication involves looking for extra or missing words in this sentence. Spelling errors and extra/missing words can cause the sentence to no longer make sense and therefore no longer provide the proper instruction for the body, causing Lesch-Nyhan syndrome. Some labs in the United States offer both sequencing and deletion/duplication of the HPRT1 gene. Some labs in the United States offer either sequencing or deletion/duplication of the HPRT1 gene. Some labs also look for the particular spelling error identified when an HPRT1 gene mutation is known in the family.

Enzyme analysis and genetic testing for Lesch-Nyhan syndrome are typically ordered by a geneticist and genetic counselor after seeing them for an appointment. A clinic appointment typically involves a complete review of the patient’s medical history, a three generation family history that documents health problems and genetic conditions, a detailed physical examination, discussion of recommended testing, and consent for genetic testing if the patient/guardian is interested. Sometimes this happens in one clinic visit, and sometimes this happens over the span of a few clinic visits. Each clinic is different. In terms of insurance, sometimes the clinic checks with your insurance, and sometimes it is your responsibility to call your insurance. As stated earlier, each clinic operates differently. If enzyme analysis or genetic testing are pursued, a blood sample and signed paperwork is sent to a laboratory that performs the testing. Results are then sent back to the geneticist and genetic counselor who contact the patient/guardian to explain the results.

You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Clinical research for Lesch-Nyhan syndrome can be found on the following sites:

Lesch-Nyhan syndrome occurs in about 1 in 380,000 people. It occurs almost exclusively in boys.

The best person to diagnose Lesch-Nyhan syndrome and discuss the symptoms is a medical geneticist (a specialist in inherited/genetic conditions) or pediatric neurologist (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologist in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

Most children with Lesch-Nyhan syndrome develop self-injurious behavior around 2-3 years of age. Some children develop these behaviors during the first year of life, and some children don’t display these behaviors until they are much older.

The best person to diagnose Lesch-Nyhan syndrome and discuss the symptoms is a specialist in medical genetics (a specialist in inherited/genetic conditions) or pediatric neurology (a specialist in conditions of the nervous system for children). Medical geneticists and pediatric neurologist in an area can be found by talking to doctors about who they would recommend or using the “Find Genetic Services” function at the American College of Medical Genetics.

HPRT (hypoxanthine-guanine phosphoribosyltransferase) enzyme activity test can be done using either a blood sample or skin cells (fibroblasts) from a skin biopsy.

Genetic testing for Lesch-Nyhan syndrome typically involves using a blood sample. Some laboratories accept saliva samples; it is best to call the lab to see if they accept a saliva sample beforehand or speak with your geneticist or genetic counselor.

To learn more about testing for Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Lesch-Nyhan syndrome is caused when there is a change in the HPRT1 gene on the X chromosome. The protein produced from the HPRT1 gene is an enzyme called hypoxanthine-guanine phosphoribosyltransferase (HPRT). Some changes (mutations) in the HPRT1 gene, cause the HPRT enzyme to not work properly, work at very low levels, or not work at all. Typically all people with a “severe” HPRT1 gene mutation have Lesch-Nyhan syndrome.

Sometimes there are mutations in HPRT1 that allow more of the enzyme to be made and work better, although still not to normal levels. These mutations can cause HPRT-related hyperuricemia and HPRT-related gout. Both of these conditions are caused by partial HPRT enzyme deficiency. The specific HPRT1 gene mutations are less severe and people have lower than normal levels of the needed protein (HPRT enzyme), but not as low as people with Lesch-Nyhan syndrome.

HPRT-related hyperuricemia may cause pain and swelling in joints (gout), crystals in the urine (this can be seen on urine test), and kidney stones. Sometimes kidney disease may occur. Males affected with this condition usually show symptoms in childhood. People with this do not show the neurological or behavioral issues seen in Lesch-Nyhan syndrome.

HPRT-related gout (also known as Kelley-Seegmiller syndrome) explains less than 2% of adult males with gout.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

Yes. There is an available technology called preimplantation genetic diagnosis (PGD). This is available if a HPRT1 gene mutation is known in the family. If some embryos are made in the laboratory using mother’s egg cells and father’s sperm cells (in vitro fertilization-IVF), genetic testing can be performed to see if the HPRT1 gene mutation is present. The female embryos or male embryos that don’t have the HPRT1 gene mutation can then be implanted in the mother. If one is interested in pursuing this, they can speak with a genetic counselor who specializes in preimplantation genetic diagnosis and/or assisted reproductive technology. Genetic counselors can be found using the website for the National Society of Genetic Counselors under "Find a Counselor".

Female carriers of Lesch-Nyhan syndrome generally do not have symptoms. However, they may have increased uric acid in their urine that can lead to symptoms of gout and/or kidney stones when they are older.

Lesch-Nyhan syndrome (LNS) almost always occurs in boys. It is inherited in an X-linked recessive manner. The HPRT1 gene is located on the X chromosome. Because boys only have one X chromosome (the other is the Y chromosome), if their HPRT1 gene has a change and is not working correctly, they have (LNS). Because females usually have two X chromosomes, and therefore two copies of the HPRT1 gene, if one copy has a change and is not working correctly, their other copy can usually compensate and make enough of the gene product for there to not be symptoms.

As of January 11, 2016, there have been less than ten females reported to be actually affected with Lesch-Nyhan syndrome. These females all had something called “skewed inactivation of the X-chromosome.” A female has two X chromosomes in every cell. One X chromosome (and therefore one HPRT1 gene) is randomly inactivated in every cell. In these affected females, one of their X chromosomes in every cell has a HPRT1 gene mutation. In skewed inactivation of the X-chromosome, more cells have the “normal” X chromosomes inactivated, and more cells have the X chromosomes with the HPRT1 gene mutation activated. Because these females have more X chromosomes with the HPRT1 gene mutation that are active, they are actually affected with Lesch-Nyhan syndrome. Again, this is very rare.

To learn more about the genetics of Lesch Nyhan syndrome, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

To establish the extent of disease and needs in an individual diagnosed with Lesch-Nyhan syndrome, the following evaluations are recommended:

There are other names for Lesch-Nyhan syndrome (LNS). They include the following:

There are other conditions besides Lesch-Nyhan syndrome caused by HPRT1 gene mutations. These include HPRT-related hyperuricemia and HPRT-related gout. Both of these conditions are caused by partial HPRT ((hypoxanthine-guanine phosphoribosyltransferase) enzyme deficiency. The specific HPRT1 gene mutations cause people to have lower than normal levels of the needed protein (HPRT enzyme), but not as low as people with Lesch-Nyhan syndrome.

HPRT-related hyperuricemia may cause pain and swelling in joints (gout), crystals in the urine (this can be seen on urine test), and kidney stones. Sometimes renal (kidney) disease may occur. Males affected with this condition usually show symptoms in childhood. Female carriers may develop features of this condition later in life. People with this do not show the neurological or behavioral issues seen in Lesch-Nyhan syndrome.

HPRT-related gout (also known as Kelley-Seegmiller syndrome) explains less than 2% of adult males with gout.

To learn more about the genetics of Lesch-Nyhan syndrome and these variants, speak with a geneticist or genetic counselor. You can find a genetics clinic near you by searching the American College of Medical Genetics. To find a genetic counselor search on the National Society of Genetic Counselors under "Find a Counselor".

There are support groups for Lesch-Nyhan syndrome. Some are specific for the condition, and some are for features of the condition. They are the following:

There are other genetic conditions that are similar to Lesch-Nyhan syndrome due to their similarities with self-injurious behavior and developmental delay. Conditions in which self-injurious behavior is also seen include nonspecific intellectual disability, autism, Rett syndrome, Cornelia de Lange syndrome, Tourette syndrome, familial dysautonomia, and several psychiatric conditions. However, of these, only individuals with Lesch-Nyhan syndrome, Cornelia de Lange syndrome, and familial dysautonomia regularly display loss of tissue as a result of the behavior. These conditions are described in more detail below. Specific finger and lip biting is characteristic of Lesch-Nyhan syndrome.