Lesch-Nyhan syndrome ... (Lesch-Nyhan syndrome) - Gen HPRT1
Lesch-Nyhan is a process that affects almost exclusively males, characterized by neurological and behavioral anomalies and excessive formation of uric acid, which can accumulate leading to gouty arthritis, or kidney stones or bladder . Neurological disorders include involuntary muscle movement disorders such as dystonia, spasmodic movements (chorea), and shaking of the limbs (ballismus). For these reasons, those affected usually can not walk and require the use of a wheelchair. Self - injury, including biting and head banging, the problem is most common and distinctive in people with Lesch-Nyhan syndrome behavior.
This process is due to mutations in the gene HRPT1, located on the long arm of the X chromosome (Xq26.1). This gene encodes the enzyme hypoxanthine-phosphoribosyl 1, which is involved in purine metabolism, making recycling when nucleic acids (RNA or DNA) are degraded. Purines recycling ensures that the cells have an abundant supply of amino acids in the coding DNA and RNA.
There are more than 200 mutations in the gene responsible HPRT1 Lesch-Nyhan syndrome. These mutations include nucleotide changes, insertions or deletions. that result encoding nonfunctional January 1, or low function-hypoxanthine phosphoribosyltransferase. Consequently, purines from nucleic acids not recycled, causing excessive accumulation of uric acid in the form., Which may lead to gouty arthritis, kidney stones and vesivcales calculations. However, it is unclear how functional enzyme deficiency leads to the characteristic neurological and behavioral problems of Lesch-Nyhan syndrome.
For reasons not well understood, the deficiency of this enzyme is associated with a deficiency of dopamine in the central nervous system. Dopamine is involved in controlling movements and emotional behaviors, so in patients with motor problems and other disorders of the central nervous system appear. Some patients with mutations in the gene HPRT1 produce a functional enzyme, and are considered to have variant Lesch-Nyhan syndrome, with signs and symptoms milder than usual syndrome. These mutations have also been associated with gouty arthritis called "related HPRT1 drop", Kelley-Seegmiller or syndrome in which there are no changes in the nervous system.
This process is inherited sex - linked recessive, because the gene is located on chromosome X. Having males one X chromosome, the alteration of this single gene is sufficient for the process is revealed. In women, having two X chromosomes, the mutation must occur on both chromosomes to express syndrome. For this reason, males are affected much more frequently than women, because it is very rare that they have two copies of the gene on both X chromosomes altered. A feature of these processes linked to chromosome X, is that parents can not pass this genetic trait to their children.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Lesch-Nyhan syndrome, by complete PCR amplification of the exons of the gene HPRT1, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).