Lesch-Nyhan syndrome

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.

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.

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.