The symptoms of Lesch-Nyhan syndrome may become apparent as early as six months of age. Earlier urate crystal formation, resulting from abnormally increased levels of uric acid in the urine, leads to the presence of orange colored deposits (“orange sand”) in the diapers of infants with this disorder. This may be the first manifestation of Lesch-Nyhan syndrome, but it is seldom recognized in early infancy.
Urate stones may develop in the kidneys of infants with Lesch-Nyhan syndrome as a result of excessive amounts of uric acid that are excreted as sodium urate. These stones may cause blood to appear in the urine (hematuria) and increase the risk of urinary tract infections. Urate crystals may also be found in the joints, but in general, it is not until the late teens or adulthood that untreated patients with Lesch-Nyhan syndrome experience recurring episodes of Pain and swelling of the joints, just like those of adults with gout. These episodes may become progressively more frequent once they begin.
In older children with this disorder, deposits of sodium urate may collect in cartilaginous tissues in joints and in the ears; in the ears, they form visible “bulges” called tophi. This is the picture commonly known as gout.
Neurological symptoms associated with Lesch-Nyhan syndrome usually begin before the age of 12 months. These may include involuntary writhing movements of the arms and legs (dystonia) and purposeless repetitive movements (chorea) such as flexing of the fingers, raising and lowering of the shoulders, and/or facial grimacing. Infants who had previously been able to sit upright typically lose this ability. Initially, muscles may be soft (hypotonia) and lead to difficulty in holding the head in an upright position. Affected infants may fail to reach developmental milestones such as crawling, sitting or walking (developmental delay). Eventually, most children with Lesch-Nyhan syndrome experience abnormally increased muscle tone (hypertonia) and muscle rigidity (spasticity). Deep tendon reflexes are increased (hyperreflexia). Intellectual disability may also occur and is typically moderate. However, accurate evaluation of intelligence may be difficult because of poorly articulated speech (dysarthria). Some patients have normal intelligence.
The most striking feature of Lesch-Nyhan syndrome, which has been observed in approximately 85 percent of patients, is self-mutilation. These behaviors most often begin between the ages of two and three years. However, they can also develop during the first year of life or much later during childhood. Self-injurious behavior may include repeated biting of the lips, fingers, and/or hands, and repetitive banging of the head against hard objects. Some children may scratch their face repeatedly. However, individuals with Lesch-Nyhan syndrome are not insensitive to pain. Additional behavioral abnormalities include aggressiveness, vomiting, and spitting. Self-mutilating behaviors regularly lead to loss of tissue.
Children with Lesch-Nyhan syndrome may have Difficulty swallowing (dysphagia) and may be difficult to feed. Vomiting is common, and most affected children are underweight for their age. Additional symptoms may include Irritability or screaming. Some children with Lesch-Nyhan syndrome may also develop a rare Anemia known as megaloblastic anemia.
Another symptom of Lesch-Nyhan syndrome may be a severe muscle spasm that causes the back to arch severely and the head and heels to bend backward (opisthotonos). Affected children may also experience hip dislocation, fractures, abnormal curvature of the spine (scoliosis) and/or permanent fixation of several joints in a flexed position (contractures).
Female carriers usually do not have symptoms of the disorder, but may develop gout later in life as a result of untreated excess uric acid in the blood (hyperuricemia).