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| DiseaseID |
HGD13 |
| Genetic
Disorder |
Lesch-Nyhan syndrome
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| Gene
Name |
HPRT1 |
| Description |
Lesch-Nyhan syndrome, a genetic disorder, causes a deficiency of an enzyme called hypoxanthine-guanine phosphoribosyl transferase (HPRT). This leads to a toxic build-up of uric acid in the body, which affects the kidneys, joints, and nervous system. What's so striking (and scary) about Lesch-Nyhan syndrome is that self-injury--biting the lips and fingers, banging the head--is a symptom.
Lesch-Nyhan syndrome occurs in approximately 1 in 380,000 individuals. It affects people of all ethnic backgrounds. A mutation in the HPRT1 gene on the X chromosome causes the syndrome. Because Lesch-Nyhan syndrome is an X-linked disorder, it occurs most often in boys.
Mutations of the HPRT1 gene cause three main problems. First is the accumulation of uric acid that normally would have been recycled into purines. Excess uric acid forms painful deposits in the skin (gout) and in the kidney and bladder (urate stones). The second problem is self-mutilation. Affected individuals have to be restrained from biting their fingers and tongues. Finally, there is mental retardation and severe muscle weakness
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| Symptoms |
An infant born with Lesch-Nyhan syndrome appears normal at first. Beginning around age 3 to 6 months, however, he starts to develop symptoms such as:
• weak muscle tone (he has difficulty holding up his head or sitting)
• uncontrollable, abnormal muscle movements (flexing, jerking, flinging, or flailing)
• muscle stiffness
• urine that looks like it contains orange sand (uric acid crystals in the urine)
• difficulty speaking
• severe gout
• kidney problems
• compulsive self-injury (banging the head, or biting the lips, tongue, and fingers)
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| Causes |
Lesch-Nyhan syndrome is inherited as an X-linked trait . Therefore, the disease is seen mainly in males. It is characterized by increased blood and uric acid levels and by the absence of the enzyme hypoxanthine guanine phosphoribosyltransferase (HGP).
Males with Lesch-Nyhan have delayed motor development followed by bizarre, sinuous movements and increased deep tendon reflexes. A striking feature of Lesch-Nyhan syndrome is self-destructive behavior characterized by chewing off fingertips and lips, if not restrained.
The excess uric acid levels cause children to develop gout-like swelling in some of their joints. In some cases, renal dysfunction develops because of the excess uric acid levels. |
| Diagnosis |
Diagnosis of Lesch-Nyhan syndrome is usually suggested by the child’s symptoms, such as abnormal muscle movements.
Parents may notice the "orange sand" in an infant's diaper, for example.
A blood or urine test can check uric acid levels. Another blood test can be conducted to check HPRT enzyme levels and confirm a diagnosis (a low level would mean testing positive for Lesch-Nyhan syndrome.) DNA testing can also be done to look for mutation in the HPRT1 gene -- another way to confirm diagnosis.
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| Treatment |
Diagnosis of Lesch-Nyhan syndrome is usually suggested by the child’s symptoms, such as abnormal muscle movements.
Parents may notice the "orange sand" in an infant's diaper, for example.
A blood or urine test can check uric acid levels. Another blood test can be conducted to check HPRT enzyme levels and confirm a diagnosis (a low level would mean testing positive for Lesch-Nyhan syndrome.) DNA testing can also be done to look for mutation in the HPRT1 gene -- another way to confirm diagnosis. |
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