Lesch–Nyhan syndrome

The Lesch -Nyhan syndrome ( LNS), also known under the synonyms of hyperuricemia syndrome and Hyperurikose, is a metabolic disease that results from a genetic defect which is inherited as an X-linked recessive. The syndrome is relatively rare: Since its first description in 1964 by pediatrician William L. ( "Bill" ) Nyhan and student Michael Lesch are over 150 documented cases. It affects almost exclusively boys or men. The syndrome occurs with an average frequency of 1:100,000 to 1:50,000.

Genetics and pathophysiology

The reason for the Lesch -Nyhan syndrome is a greatly reduced activity of the enzyme hypoxanthine - guanine phosphoribosyl transferase ( HGPRT or HPRT), which is caused by a mutation of the HPRT1 gene on the X chromosome ( Xq26 - q27.2 ). In addition to the Lesch -Nyhan syndrome and other disorders caused by mutations of this enzyme are known. HGPRT is involved in purine metabolism of hypoxanthine and guanine, which are nucleosides as building blocks for DNA and RNA; the decreased activity has a strong increase of uric acid breakdown product of purines that result.

The Lesch -Nyhan syndrome is an X-linked recessive trait. Since men have only one X chromosome, it comes to the Lesch -Nyhan syndrome, as soon as this is concerned. Women can get only in extremely rare cases, the Lesch -Nyhan syndrome, since they have two X chromosomes and both would be affected. However, they can be carriers of chromosomal specificity. Only if the father and mother inherit an affected X chromosome, that is the father of the Lesch -Nyhan syndrome ill and the mother is to be a carrier of a chromosome affected, and women can suffer.

Disease

In about the tenth month after the birth of a conspicuous position of the legs is noticeable in babies with Lesch -Nyhan syndrome and the child is prone to motion poverty and development gaps. Increased Harnrückstand in the diaper can also be the first sign.

While only an increased uric acid secretion is observed with a slight manifestation of the disease, occurs in severe forms also to typical self-injury (often lip and finger biting as a way to auto stimulation) and cognitive impairments. In the auto-aggressive behavior on the extremities should be noted that the affected people just bite into a hand.

In addition to the described auto-aggression can also show foreign aggression ill people. This depends as a rule against emotionally related caregivers (parents, siblings, friends, carers ).

Diagnostics

The diagnosis is often done by the clinical picture. Elevated uric acid levels in blood and urine are more, but non-specific instructions. The diagnosis is confirmed by measuring the HGPRT activity in the blood and tissues, which is strongly reduced and maintained by the genetic detection of HPRT mutation. Such is already prenatally possible.

The Lesch -Nyhan syndrome is not incurable. Treatment with drugs ( allopurinol), which inhibit the Purinabbau, and a special diet the symptoms are treatable to some extent. 5 -Hydroxytryptophan - shares can improve the athetosis. In some cases, removal preventive of the deciduous teeth is necessary. Untreated die boy with the Lesch -Nyhan syndrome within the first years of life and do not reach adolescence. New approaches based on deep brain stimulation promise relief from the symptoms to the complete set of self- attacks.