Lesch-Nyhan syndrome
Classification according to ICD-10 | |
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E79.1 | Lesch-Nyhan syndrome |
ICD-10 online (WHO version 2019) |
The Lesch-Nyhan syndrome ( LNS ), also under the definition hyperuricemia syndrome and Hyperurikose known, is a metabolic disorder resulting from a genetic defect , the X-linked recessive inherited. The syndrome is comparatively rare: since it was first described in 1964 by the pediatrician William L. ("Bill") Nyhan and the student Michael Lesch, over 150 cases have been documented. Almost exclusively boys and men are affected. The syndrome occurs with an average frequency of 1: 100,000 to 1: 50,000.
Genetics and pathophysiology
Lesch-Nyhan syndrome is caused by a greatly reduced activity (<1%) of the enzyme hypoxanthine-guanine-phosphoribosyltransferase (HGPRT), which is caused by a mutation of the HPRT1 gene on the X chromosome (Xq26-q27.2) becomes. In addition to Lesch-Nyhan syndrome, other diseases caused by mutations in this enzyme are known. If the activity of this enzyme is partially preserved, there is a Kelley-Seegmiller syndrome . HGPRT is involved in the purine metabolism of hypoxanthine and guanine , which as nucleosides are building blocks for DNA and RNA ; the reduced activity leads to a sharp increase in uric acid , a breakdown product of purines.
Lesch-Nyhan syndrome is inherited in an X-linked recessive manner. Since men only have one X chromosome, Lesch-Nyhan syndrome occurs as soon as it is affected. Women can only develop Lesch-Nyhan syndrome in extremely rare cases because they have two X chromosomes and both should be affected. However, they can be carriers of the chromosomal particularity. Women can only become ill if the father and mother inherit an affected X chromosome, i.e. if the father suffers from Lesch-Nyhan syndrome and the mother is the carrier of an affected chromosome.
Clinical picture
In about the tenth month after birth , babies with Lesch-Nyhan syndrome have a noticeable stance on their legs and the child tends to be sedentary and delayed in development, movement disorders up to choreoathetosis . An increased urine residue in the diaper can also be a first sign.
While only an increased uric acid excretion can be observed in a mild form of the disease , typical self- injuries (often lip and finger bites as a possibility for autostimulation ) and cognitive impairments occur in more severe forms . With the auto-aggressive behavior on the extremities , it should be noted that the affected people only bite one hand.
In addition to the described autoaggression, sick people can also show aggressive behavior from others. This is usually aimed at emotionally close reference persons (parents, siblings, friends, carers).
Diagnosis
The diagnosis is often based on the clinical picture. Elevated uric acid levels in the blood and urine are further, but unspecific indications. The diagnosis is confirmed by the measurement of the HGPRT activity in the blood and tissue, which is greatly reduced, and confirmed by the genetic detection of the HPRT1 mutation. This is also possible prenatally .
Therapy, prognosis
The Lesch-Nyhan syndrome cannot be cured. Treatment with medication ( allopurinol ) that inhibit the breakdown of purines and a special diet means that some of the symptoms can be treated. 5-Hydroxytryptophan can improve the athetosis . In some cases, preventive removal of the milk teeth is necessary. If left untreated, boys with Lesch-Nyhan syndrome die within the first few years of life and do not reach adolescence. New approaches based on deep brain stimulation promise alleviation of symptoms through to the complete cessation of self-attacks.
literature
- Klaus Sarimski: Developmental Psychology of Genetic Syndromes. 3. Edition. Hogrefe, Göttingen 2003, ISBN 3-8017-1764-X .
- Regine Witkowski, Otto Prokop , Eva Ullrich, Gundula Thiel: Lexicon of Syndromes and Malformations. 7th edition. Springer, 2003, ISBN 3-540-44305-3 .
- Manfred Dworschak: Mortal enemy in the head . In: Der Spiegel. 6/2008, pp. 116-119. ISSN 0038-7452
- RJ Torres, JG Puig: Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. In: Orphanet Journal of Rare Diseases. Volume 2, 2007, p. 48, ISSN 1750-1172 . doi: 10.1186 / 1750-1172-2-48 . PMID 18067674 . PMC 2234399 (free full text). (Review).
Web links
- Lesch-Nyhan syndrome. In: Online Mendelian Inheritance in Man . (English)
- Lesch-Nyhan Syndrome at emedicine.com (engl.)
Individual evidence
- ↑ Michael Lesch, WL Nyhan: A familial disorder of uric acid metabolism and central nervous system function. In: The American journal of medicine. (AJM). Orlando 1964, 36, pp. 561-570, PMID 14142409 ISSN 0002-9343 .
- ↑ DGSculley, PADawson, BTEmmerson, RBGordon: A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. In: Human genetics. (Hum Genet.). Berlin 90.1992,3 (Nov), pp. 195-207, PMID 1487231 ISSN 0340-6717 .