Lesch-Nyhan syndrome

Related Terms

Aggressive behaviors, ballismus, behavioral problems, choreoathetosis, choreoathetosis self-mutilation syndrome, cognitive dysfunction, complete HPRT deficiency, complete hypoxanthine-guanine phosphoribosyltransferase deficiency, deficiency of guanine phosphoribosyltransferase, deficiency of hypoxanthine phosphoribosyltransferase, dystonia, gouty arthritis, HGPRT deficiency, HPRT deficiency, HPRT deficiency-neurologic variant, HPRT1 deficiency, HRH, HRND, hyperreflexia, hyperuricemia, hypoxanthine guanine phosphoribosyltransferase 1 deficiency, hypoxanthine-guanine phosphoribosyl transferase, hypoxanthine-guanine phosphoribosyltransferase deficiency, impulsive behaviors, juvenile gout-choreoathetosis-mental retardation syndrome, juvenile hyperuricemia syndrome, Kelley-Seegniller syndrome, Lesch-Nyhan disease, LNS, nephrolithiasis with renal failure, neurologic disability, overproduction of uric acid, primary hyperuricemia syndrome, self-injurious behaviors, spasticity, tophi, total HPRT deficiency, total hypoxanthine-guanine phosphoribosyl transferase deficiency, X-linked hyperuricemia, X-linked primary hyperuricemia, X-linked uric aciduria enzyme defect.

Background

Lesch-Nyhan syndrome (LNS) is a rare genetic disorder that affects the joints, muscles, and brain. LNS is characterized by the overproduction and accumulation of uric acid, a waste product of normal chemical processes found in blood and urine. The overproduction of uric acid can cause gouty arthritis from the accumulation of uric acid in the joints, kidney stones, and bladder stones. Problems with the nervous system and behavioral disturbances are also characteristic of this disorder. Abnormal involuntary muscle movements such as flexing, jerking, and flailing are often displayed by people affected with this disorder. People with LNS usually cannot walk, require assistance to sit, and are often wheelchair-bound. Self-injury, including biting and head banging, is the most common and distinctive behavioral problem in people with LNS.
LNS is caused by mutations or defects in the HPRT1 gene, which lead to a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1). Insufficient levels of the HPRT1 enzyme cause a buildup of uric acid in bodily fluids. Uric acid is a waste product of normal chemical processes in the body found in the blood and urine. When uric acid accumulates in the joints, kidneys, central nervous system, and other tissues, damage may occur. A high uric acid level may appear prior to the development of high blood pressure, heart disease, or chronic kidney disease, but it is often unclear whether a high uric acid level is a direct cause or merely an early warning sign of these conditions.
Symptoms of LNS include gout, which is characterized by high levels of uric acid, painful joints, poor muscle coordination, and moderate intellectual disabilities. Individuals with LNS also demonstrate self-mutilating behaviors, including lip and finger biting, which usually appear during the second year of life.
LNS is inherited or passed down among family members as an X-linked recessive trait. This means that the defective gene is located on the X chromosome, which is one of the two types of sex chromosomes.
The prevalence of LNS is about one in 380,000 people. The condition mainly affects males, because it is X-linked, although cases have been reported in females. LNS does not appear to affect any one ethnicity more than another.
LNS is apparent at birth. There is no cure for the disorder. Instead, treatment aims to reduce symptoms and prevent complications. The prognosis for people with LNS is poor, with most individuals experiencing fatal kidney problems during the first or second decade of life. Few people with LNS live beyond 40 years of age.

Signs and symptoms

General: Individuals with Lesch-Nyhan syndrome (LNS) tend to develop normally in the womb and shortly after birth, but symptoms progress as the patient gets older. LNS is typically apparent in males at birth. Decreased muscle tone and developmental delays are apparent by about 3-6 months of age. The most obvious feature seen in the general physical examination is growth retardation. Somatic growth is affected more than head circumference; bone age is affected only slightly. Puberty is delayed or absent. Behavioral disturbances and problems with the nervous system are also characteristic of this disorder. Abnormal involuntary muscle movements such as flexing, jerking, and flailing are often displayed by people affected with this disorder. Men with LNS usually cannot walk, require assistance to sit, and are often wheelchair-bound. Self-injury, including biting and head banging, is the most common and distinctive behavioral problem in people with LNS. Cognitive function is impaired, with intelligence quotient (IQ) scores of approximately 60. Although females have LNS rarely, those who do tend to have mild symptoms that occur later in life and may include increased excretion of uric acid, a waste product of normal chemical processes found in blood and urine. Further discussion on the symptoms associated with LNS will relate to males.
Cognitive disorders: Most men with LNS have moderate intellectual disabilities. Intelligence quotient (IQ) scores are about 60 in patients with this disorder (compared to the average IQ between 90 and 100). Cognitive symptoms of LNS tend to emerge between two and three years of age. These may include self-injuring behaviors, such as biting the fingers, hands, lips, and cheeks, and persistent banging of the head or arms and legs. Additional behavioral problems may include aggressiveness, acting on impulse rather than on thought, attention deficit, vomiting, spitting, and involuntary uttering of obscene words.
Developmental disorders: Men with LNS tend to have developmental delays. Children affected by LNS have delayed attainment of developmental milestones such as sitting and standing. Most individuals with this condition never learn to walk. They may require assistance to sit and are often wheelchair-bound. Growth and puberty are generally delayed in individuals with LNS.
Gouty arthritis: The buildup of uric acid in the joints leads to a condition known as gouty arthritis. This condition is arthritis or painful joints caused by the accumulation of uric acid crystals. Acute gout attacks are characterized by a rapid onset of pain in the affected joint, followed by warmth, swelling, reddish discoloration, and marked tenderness. Tenderness can be so intense that even a blanket touching the skin over the affected joint can be unbearable. Patients can develop fever with acute gout attacks. These painful attacks usually subside in hours to days, with or without medication. In rare instances, an attack can last for weeks. Most patients with gout will experience repeated flare-ups of arthritis over the years.
Kidney and bladder stones: The buildup of uric acid leads to the formation of painful stones in the kidneys, ureters, and bladder. These stones often do not cause any symptoms. Usually, the first symptom of a kidney stone is extreme pain, which begins suddenly when a stone moves in the urinary tract and blocks the flow of urine. Typically, a person feels a sharp, cramping pain in the back and side in the area of the kidney or in the lower abdomen. Sometimes nausea and vomiting occur. Later, pain may spread to the groin.
Neurological disorders: People with LNS tend to have poor muscle tone, which may cause coordination problems that resemble cerebral palsy, a disorder that affects muscle tone, movement, and motor skills. They also have involuntary movements called choreoathetosis, flinging of the limbs, facial grimacing, spasticity (continuous contraction of certain muscles), overactive reflexes, opisthotonos (abnormal posturing), and extensor plantar reflexes (certain abnormal reflexes).
Tophi: Uric acid may also accumulate in the skin in deposits called tophi, which are solid collections of uric acid crystals. These tophi are deposited in the joints and cause inflammation and gout.
Other: Males with LNS may have underdeveloped testicles, which may be accompanied by loss of function.

Diagnosis

General: If not detected at birth by a physician, caregivers of individuals with Lesch-Nyhan syndrome (LNS) generally seek medical care when the child is 3-12 months old and exhibits increased or decreased muscle tone, involuntary movements, or poor motor skill development. Between the ages of six and 18 months, involuntary movements become more obvious. Some individuals with LNS will require medical care when caregivers notice "orange sand," that is, uric acid crystals, in the diapers. Most of the uric acid is filtered out by the kidneys and passes out of the body in urine; a small amount also passes through stool. But if too much uric acid is being produced or if the kidneys are not able to remove it from the blood normally, the level of uric acid in the blood increases. High levels of uric acid in the blood can cause solid crystals to form within joints, and, if left untreated, kidney failure. Other patients may require medical care only after developing kidney, ureter, or bladder stones, blood in the urine, or kidney failure.
Blood tests: A complete blood count should be used to evaluate the presence of megaloblastic anemia, a blood disorder that occurs when the levels of red blood cells becomes too low. Levels of vitamin B12, folate, and iron should also be evaluated. Blood tests can be used to detect increased levels of uric acid and decreased HPRT1 enzyme activity.
Imaging studies: Ultrasound, a noninvasive procedure that uses sound waves to create a moving image of internal structures, can be used to evaluate the presence of stones in the kidney, ureters, and bladder in patients with LNS. Imaging studies of the spine may reveal early signs of degenerative joint disease, the "wear and tear" of joint surface cartilage, which is usually accompanied by osteophytes (overgrowths of bone), narrowing of the joint space, sclerosis or hardening of bone at the joint surface, and deformity in joints.
Neurological exam: A neurological exam assesses motor and sensory skills, the functioning of one or more cranial nerves, hearing and speech, vision, coordination and balance, mental status, and changes in mood or behavior, among other characteristics.
Urine tests: Analysis of a urine sample can evaluate the level of uric acid. Reference values for 24-hour urinary uric acid vary from laboratory to laboratory but are generally found within the 250-750 milligram range. Uric acid levels in individuals with LNS are typically elevated.
Genetic testing: If LNS is suspected, a deoxyribonucleic acid (DNA) test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the HPRT1 gene. If this defect is detected, a positive diagnosis is made.
Prenatal DNA testing: If there is a family history of LNS, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose LNS. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.
During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the HPRT1 gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

Anemia: People with Lesch-Nyhan syndrome (LNS) may develop a type of anemia (low numbers of red blood cells) called megaloblastic anemia, which results from inhibition of DNA synthesis in red blood cell production, usually because of a deficiency of vitamin B12. Some research suggests that individuals with LNS have normal levels of vitamin B12 and therefore may not be affected by this cause of anemia, which usually occurs because the digestive system is unable to absorb the B12.
Developmental disorders: Individuals with LNS tend to have developmental delays. Children affected by LNS have delayed attainment of developmental milestones such as sitting and standing. Most individuals with this condition never learn to walk. They may require assistance to sit and are often wheelchair-bound. Growth and puberty are generally delayed in individuals with LNS.
Heart problems: Complications of gout (gouty arthritis) include coronary artery disease, heart problems, congestive heart failure, and high blood pressure.
Kidney failure: In severe cases, individuals with LNS may develop kidney failure from a buildup of uric acid crystals in the urinary tract. This buildup of crystals may develop into kidney stones.
Neurological disorders: People with LNS tend to have poor muscle tone, which may cause coordination problems that resemble cerebral palsy, a disorder that affects muscle tone, movement, and motor skills. People with LNS usually cannot walk, require assistance to sit, and are generally wheelchair-bound.
Pain: Deposits of uric acid in the joints, skin, kidneys, ureters, and bladder can cause severe pain in individuals with LNS.
Pneumonia: Poor muscle tone may contribute to swallowing problems, which can cause food or liquid to enter the lungs and may ultimately cause pneumonia.
Sudden death: A significant proportion of individuals with LNS die of sudden death. The cause for this is yet unknown but may be related to breathing problems caused by poor muscle tone.

Treatment

General: There is currently no known cure for Lesch-Nyhan syndrome (LNS). Instead, treatment focuses on the reduction of symptoms and prevention of complications. With optimal medical care, affected individuals typically live into their thirties. While many with LNS die from aspiration pneumonia or complications from chronic kidney damage and kidney failure, a significant proportion of patients die suddenly and unexpectedly from unknown causes.
Medications: Allopurinol is a drug commonly used for the treatment of gout, a disease characterized by high levels of uric acid. This drug blocks the metabolism of certain substances called hypoxanthine and xanthine into uric acid, thereby decreasing overall production of uric acid. Use of this therapy may cause excessive amounts of hypoxanthine and xanthine, which may cause kidney or bladder stone formation. Therefore, care should be taken to avoid dehydration in individuals who are susceptible to stone formation, particularly those taking allopurinol. The dose of allopurinol may require adjustment in individuals with kidney disease. Even if allopurinol is started early in life, there is no evidence of its effect on any other symptoms of LNS, such as neurological problems. Allopurinol should not be used with certain types of drugs that also treat gout, such as probenecid. This is because these drugs increase the excretion of uric acid in the urine, which can lead to kidney, ureter, and bladder stone formation. The side effects of allopurinol are rare, though they are significant when they occur. A small percentage of people develop a rash and must discontinue the drug.
Medications such as baclofen, which is a muscle relaxer, and benzodiazepines, a class of drugs that induce anticonvulsive activity, may be used to manage spasticity, or the persistent contraction of certain muscles, seen in LNS.
Medications such as gabapentin and carbamazepine, which are both mood-stabilizing drugs, may help decrease self-injury and other behavioral problems commonly seen in LNS. The most common side effects observed in individuals taking gabapentin include dizziness, drowsiness, coordination problems, fever, nausea, vomiting, fluid retention, and unusual eye movements. Gabapentin has been used in children and young adolescents in countries outside the United States. In the United States, gabapentin is approved only for use in patients over the age of 12. For carbamazepine, serious side effects include dangerously low red and white blood cell counts. Severe skin reactions and liver abnormalities, such as hepatitis, may occur. Low sodium levels and thyroid abnormalities have been described. More common minor side effects include dizziness, unsteadiness, nausea, and vomiting. Carbamazepine should not be used in patients with a history of previous bone marrow depression or hypersensitivity to the drug, or in patients who are taking drugs to treat depression or other mood disorders.
Medications to avoid: Certain drugs, such as probenecid, that reduce the concentration of uric acid in the blood should be avoided in individuals with LNS. This is because these drugs increase the excretion of uric acid in the urine, which can lead to kidney, ureter, and bladder stone formation.
Vitamin B12 supplementation: If vitamin B12 deficiency is the cause of anemia, as is the case in megaloblastic anemia, then supplementation with B12 is the standard approach. A physician should evaluate patients with anemia in order to diagnose and address the underlying cause.
Behavioral therapy: Behavioral therapy may be beneficial for individuals with self-injuring behaviors. Behavioral therapy is available to help LNS patients improve their communication and social skills, as well as their learning abilities and adaptive behaviors. Evidence suggests that behavioral therapy is most effective if it is started early in life, when the patient is 3-4 years of age or younger.
Diet: If swallowing problems develop, individuals with LNS may benefit from a diet that does not include any pure liquid foods, but rather pureed, or thickened, liquids, which reduce the risk of aspiration, or entry of food or liquid into the lungs.
Education: By law, patients with LNS must have access to education that is tailored to their specific strengths and weaknesses. According to the Individuals with Disabilities Education Act, all children with disabilities must receive free and appropriate education. According to the law, staff members of the patient's school should consult with the patient's parents or caregivers to design and write an individualized education plan. The school faculty must document the child's progress in order to ensure that the child's needs are being met.
Educational programs vary among patients. In general, most experts believe that children with disabilities should be educated alongside their nondisabled peers. The idea is that nondisabled students will help the patient learn appropriate behavioral, social, and language skills. Therefore, some LNS patients are educated in mainstream classrooms. Others attend public schools but take special education classes. Still others attend specialized schools that are equipped to teach children with disabilities.
Lithotripsy: Lithotripsy uses shock waves to physically break up kidney, ureter, or bladder stones. This procedure is generally safe. However, as with any medical procedure, complications can occur. Complications can include pieces of stone being left in the body; bleeding around the kidney, which, in rare cases, may require a blood transfusion; damage to the kidney tissue or nearby structures in the stomach area; and blockage of urine flow from pieces of stone. How well a patient does with this procedure depends on the number, size, and location of the stones. However, lithotripsy completely removes stones in most patients who have the procedure.
Occupational therapy: Patients may benefit from occupational therapy. During sessions, a therapist helps the child learn skills needed to perform basic daily tasks, such as eating, dressing, and communicating with others. Some patients work with therapists who specialize in disorders and disabilities. Parents and caregivers can ask their child's pediatrician for recommended therapists.
Protective equipment: Certain protective equipment, such as a helmet or knee pads, may be helpful in reducing self-injury in people with LNS, such as repeated banging of the head and limbs on hard surfaces.
Psychotherapy: People with LNS, most of whom have self-injury behaviors, may benefit from psychotherapy. Psychotherapy is an interactive process between an individual and a qualified mental health professional (e.g., psychiatrist, psychologist, clinical social worker, licensed counselor, or other trained practitioner). Its purpose is the exploration of thoughts, feelings, and behavior for the purpose of problem solving or achieving higher levels of functioning.
Restraints: Restraints, which are used to prevent an individual from moving his or her hands and feet, may be required to decrease the self-injury behaviors seen in most individuals with LNS. LNS is one of very few diseases for which continuous and long-term restraints are acceptable to the Joint Commission on Accreditation of Healthcare Organizations (JCAHO).
Physical therapy: According to the American Physical Therapy Association, the goal of physical therapy or physiotherapy is to improve mobility, restore function, reduce pain, and prevent further injury by using a variety of methods, including exercises, stretches, traction, electrical stimulation, and massage. Physical therapy has been reported to be useful in neurological disorders.
Surgery: Severe kidney or bladder stones may require surgical removal. Other surgical procedures may be needed in individuals with LNS for the release of persistently contracted muscles, joint problems, and spinal problems.
Caregiver support: Movement disorders confront individuals and their caregivers with many complex problems that must be managed for the patient's entire lifetime. While it may be emotionally difficult, it is important for patients and caregivers to make informed, carefully considered decisions regarding the future while the patient is capable of making his or her contribution to a planned course of action.
Adaptive equipment: Special equipment is also available for individuals with LNS. Wheelchairs, walkers, and braces may help individuals with LNS to perform daily tasks. A wheelchair is sometimes used if a person with LNS cannot walk independently. Many people with LNS can use their arms to roll the wheels of the wheelchair on their own and can move around without much difficulty. There are also motorized wheelchairs available, which may be especially useful for a child. A walker is a piece of equipment usually made out of light metal with adjustable legs. Some people with LNS can walk but have poor balance and may fall. A walker can help these people balance and get around without the use of a wheelchair. Because of the fine motor problems often associated with LNS, individuals may have a hard time using conventional eating utensils. Specially designed eating utensils are available, as are specialized tools to help perform activities of daily living.
Teeth extraction: About 60% of people with LNS eventually have their teeth extracted to prevent ongoing self-injury behaviors such as biting the fingers, lips, and cheeks.
Pain relievers: Pain relievers, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can be used to reduce pain associated with gout. Some NSAIDs include ibuprofen and naproxen. NSAIDs are safest when low doses are taken for brief periods. Side effects most commonly occur when taking large doses over a prolonged time. Some are mild and go away on their own or after reducing the dose, while others may be more serious and need medical attention. Common side effects of NSAIDs include stomach pain and heartburn; stomach ulcers; an increased bleeding tendency; headaches and dizziness; ringing in the ears; allergic reactions, such as rashes, wheezing, and throat swelling; liver or kidney problems; high blood pressure; and leg swelling.
Experimental treatments: Deep brain stimulation (DBS), a procedure in which stimulating electrodes are placed in a part of the brain called the basal ganglia, has been studied for the treatment of both poor muscle tone and self-injury behaviors. Deep brain stimulation involves a surgically implanted, battery-operated medical device (called a neurostimulator) used to deliver electrical stimulation to areas of the brain that control movement, such as the basal ganglia. The electrical charge blocks nerve signals that trigger abnormal movement. In DBS, an electrode is inserted through a small incision in the skull and implanted in the targeted area of the brain. An insulated wire is then passed under the skin in the head, neck, and shoulder, connecting the lead electrode to the neurostimulator, which is surgically implanted in the chest or upper abdomen. Side effects of deep brain stimulation include bleeding at the implantation site, depression, impaired muscle tone, infection, loss of balance, slight paralysis, slurred speech, and tingling in the head or the hands.

Integrative therapies

Currently there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of Lesch-Nyhan syndrome (LNS).

Prevention

General: Because Lesch-Nyhan syndrome (LNS) is an inherited condition, there is currently no known way to prevent the disease. However, a number of options are available for prospective parents with a family history of LNS.
Genetic testing and counseling: Individuals with LNS may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with a family history of LNS may meet with a genetic counselor to determine whether they carry the defective HPRT1 gene. Carriers can be determined through detailed family histories or genetic testing.
Known carriers of LNS may undergo genetic counseling before they conceive a child. Genetic counselors can explain the options and the associated risks of various tests, including preimplantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
Preimplantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective HPRT1 gene, and only the embryos that are not affected may be selected for implantation. Because LNS can be detected in a fetus, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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Causes

Genetic mutations: Lesch-Nyhan syndrome (LNS) is caused by mutations or defects in the HPRT1 gene, which lead to a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1).
Decreased levels of HPRT1 may lead to a buildup of uric acid in bodily fluids. Uric acid is a waste product of normal chemical processes and is normally found in the blood and urine. When uric acid accumulates in the joints, kidneys, central nervous system, and other tissues, damage may occur. The increased concentration of uric acid leads to the formation of tophi, which are solid collections of uric acid crystals. These tophi are deposited in the joints and cause inflammation and gout. Increased levels of uric acid also collect in the kidneys, ureters, and bladder, causing the formation of stones. The causes of the neurological symptoms seen in LNS are not well understood.
X-linked recessive inheritance: LNS is inherited, or passed down among family members, as an X-linked recessive trait. This means that the defective gene is located on the X chromosome, which is one of the two types of sex chromosomes. Females have two X chromosomes, while males have one X and one Y chromosome. Females inherit an X chromosome from each parent, one from the mother and one from the father, while males inherit an X chromosome from the mother and a Y chromosome from the father. Therefore males can inherit LNS only from their mothers.
Females must inherit two copies of the defective HPRT1 gene in order for the condition to occur. Males, on the other hand, need to inherit only one copy of the defective HPRT1 gene for the disease to occur. Therefore, LNS occurs more frequently in males than in females.
It is currently unknown whether LNS can occur from a spontaneous mutation.

Risk factors

Lesch-Nyhan syndrome (LNS) is inherited, or passed down among family members. Therefore, the only known risk factor is a family history of the disease. The prevalence of LNS is about one in 380,000 people. The condition does not appear to affect any one ethnicity more than another.
LNS is inherited as an X-linked recessive trait. This means that the defective gene is located on the X chromosome, which is one of the two types of sex chromosomes. Females have two X chromosomes, while males have one X and one Y chromosome. Females inherit an X chromosome from each parent, one from the mother and one from the father, while males inherit an X chromosome from the mother and a Y chromosome from the father. Females must inherit two copies of the defective HPRT1 gene in order for the condition to occur. Males, on the other hand, need to inherit only one copy of the defective HPRT1 gene for the disease to occur. Female carriers usually do not have any symptoms but occasionally develop inflammation of the joints (i.e., gout) as they get older. Mothers and sisters of LNS patients should be tested to determine whether they are carriers.

Types of the disease

Although information on different types of Lesch-Nyhan syndrome (LNS) is limited, some researchers suggest that the extent of the deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) may indicate the type of disease. Severe deficiency of HPRT1 is associated with LNS, whereas partial deficiency of the enzyme is associated with a condition called Kelley-Seegmiller syndrome, which is a variant of LNS. While LNS features accumulation of uric acid, a waste product of normal chemical processes found in blood and urine, and cognitive, behavioral, and neurological symptoms, Kelley-Seegmiller syndrome tends to feature only accumulation of uric acid, with resulting kidney stones, other kidney problems, and potentially gout. Individuals with another variant of LNS tend to be more severely affected neurologically. However, there is very limited information on this type.