What is Lesch-Nyhan Syndrome? What are its causes and Symptoms?

This is a very rare disorder found in the ratio of 1 : 400,000 males.  This disorder is due to deficiency of enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).  It is a hereditary disorder passed by the mother to the son.  The HPRT gene mainly involves in producing purines, one of the components of DNA & RNA.  Mutation in this gene causes an increase in the production of uric acid. This excessive production of uric acid causes damage to the kidney.  Other problems faced by Lesch-Lyhan Syndrome patients are poor muscle control, mental retardation and self-injuring behavior.  An affected person has to live with various physical and mental problems all throughout his life.  As the gene is located in the X-chromosome, this disorder is an X-linked inherited disease.  As such males are mostly affected by the Lesch-Lyhan Syndrome and very rarely do females develop this disease.  Females are only carriers of the defective gene and pass it on to their male child.

The symptoms of Lesch-Lyhan Syndrome start as early as three months from the birth of the child.  The first indications are that of a baby which cannot hold its head up or sit down.  The mutilating behavior starts around the 2^nd or 3^rd year.  The child may try to bite off his lips or the fingers which is a clear indication of self-injury.  Another indication is that of sand-like crystals of uric acid which are seen in the child’s diapers.  This is due to over production of uric acid which forms crystals or stones in the kidneys and bladders.  These crystals may get deposited in joints at a later stage resulting in diseases like arthritis which has a gout-like swelling and tenderness.  These stones often get mixed with urine and causes hematuria or urinary track infections. 

A patient with Lesch-Lyhan Syndrome has abnormal muscle contraction which is seen by way of loss of motor control, arching of the spine, overactive reflexes and writhing motions.  As pointed out earlier, the affected person has a tendency for self-mutilating behavior and gets irritated easily which leads to head-banging and biting off his fingers and lips.  Stress plays a major role in activating these tendencies.  There are also indications of aggressiveness, spitting, vomiting or swearing in this disorder.  The disease may, in most cases, confine the person to a wheelchair as he is unable to walk throughout his life.  Another complication is the occurrence of megaloblastic anemia which is caused due to lack of HPRT, which in turn is due to the body not utilizing the B12 vitamin.

A Lesch-Lyhan Syndrome cannot be cured and in most probability the person dies around the age of 15 – 25 yrs.  Death usually occurs due to renal failure.  The treatment for Lesch-Lyhan Syndrome consists of various methods.  The Gout is treated with allopurinol which controls the excessive amount of uric acid.  The kidney stones which are present can be treated with lithotripsy which is a technique for breaking the stones with shock waves.  Also a number of drugs are prescribed to control excessive amount of uric acid production, or to control the motor activities.  The self-mutilation effect is reduced by a varied combination of medical, physical and behavioral interventions.  Most often the teeth of the person are removed to stop the tendency of biting off the lips, tongue and fingers.  As stress is a major factor for kindling the self-mutilating tendency, it is usually recommended to prescribe aversive techniques.

The families of individuals affected by Lesch-Lyhan Syndrome are recommended to go through various testing and genetic counseling.  The preimplantation Genetic Diagnosis (PGD) test is nowadays conducted on the embryo to diagnose the genetic effects and determine the sex before implantation.  This reduces the chance of having a Lesch-Lyhan Syndrome offspring.

Diagnosing Lesch-Lyhan Syndrome at an early age is difficult as all the three indications are not developed fully.  As the child grows the three elements i.e. neurological dysfunction, self-mutilation and uric acid overproduction are identified clearly.