Alicia's research paper

Alicia Prewett
Biology 351
March 13, 2009

Lesch-Nyhan Syndrome: a genetic disease

In genetics, a biochemical disorder in which cell metabolism is nonstandard is known as a hereditary disease. A defective enzyme of which metabolism is abnormal is inherited. Therefore, the cause of these hereditary diseases are referred to as inborn errors of metabolism. Each enzyme is important in biochemical pathways of development. So as a result of a defective enzyme, the developmental pathway of a certain gene is faulty, usually resulting in a mutation or an inherited disease. The rare Lesch-Nyhan syndrome is one such genetic disease.

More specifically, Lesch-Nyhan syndrome is an inborn error of purine metabolism. A purine is a nitrogenous base that is one of the building blocks of deoxyribonucleic acid and ribonucleic acid. Adenine and guanine are examples of purines. In patients with Lesch-Nyhan syndrome, purine metabolism is abnormal and results in the overproduction and massive excretion of purine. Normal purine metabolism consists of producing uric acid. With the overproduction of purine comes an excess of uric acid, causing uric acid crystals to build up in the joints and to be micturated in the urine. The discovery of uric acid crystals in the urine is one method of diagnosing Lesch-Nyhan syndrome.

In patients with Lesch-Nyhan syndrome, there is a close relationship between uric acid overproduction and a deficiency of a specific enzyme known as hypoxanthine phosphoribosyltransferase (HPRT). “In the absence of HPRT, hypoxanthine is degraded into xanthine and uric acid in liver by xanthine oxidase.” (Lapucci 2006) Additionally, the more of the HPRT gene that’s lacking, the more severe the Lesch-Nyhan disease is. The loss of activity of the HPRT enzyme is ultimately the cause of Lesch-Nyhan syndrome. HPRT is a housekeeping enzyme. It is a major constituent in purine metabolism, and in it’s absence, the excess of purine accumulates and degrades into uric acid. The HPRT gene codes for a protein that is 219 amino acids long. HPRT is located on the X-chromosome in a region called Xq26. On the X-chromosome, the region Xq26 is simply a genetic marker.

HPRT is recessive and since it affects the X-chromosome, it only effects males. The trait can be carried in females but they are usually asymptomatic. Lesch-Nyhan syndrome patients show symptoms of “mental retardation, dysarthia, chorea, dystonia, spasticity, and ataxia.” (Jankovic 1987) The deficiency of HPRT leading to the abnormal metabolism of purine also has an undesirable effect on “somatic growth, the maturation of bone marrow stem cells into erythrocytes, and on gastrointestinal motility.” (Jinnah 2009) The lack of red blood cells, restraint of body cell growth and problematic digestive system all stem from this HPRT deficit.

However, the most remarkable symptom of patients with Lesch-Nyhan syndrome is self-mutilation and self-injurious behavior. Among other urges that contradict what patients really think or how they really feel, self-mutilation is a major demise. Lesch-Nyhan patients cannot deny urges to chew off their own fingers or to chew off their own lips. Psychologically, they also will say awful, hurtful things to the people closest to them and/or patients will often lie, especially when it hurts their own interests. Most Lesch-Nyhan patients are wheel-chair bound and constantly restrained. They can live into their early to mid-twenties but most don’t.

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