What is Lesch Nyhan Syndrome?
Lesch-Nyhan syndrome is a rare genetic disorder that is characterized by the excessive production and accumulation of uric acid, (a chemical waste product that is eliminated out of the system) in the urine and blood. The abnormal, excessive production of uric acid can result in kidney stones, gouty arthritis (due to the uric acid accumulation in the joints), and bladder stones. The patients affected with this disorder often present with abnormal involuntary muscle movements like jerking, flexing, and flailing. The condition is accompanied by the manifestation of impaired behavior and disturbances in nervous system. Other clinical features of the Lesch-Nyhan syndrome include walking disability, inability to sit without assistance, and necessity of being wheelchair-bound. They can also commonly display distinctive behavioral problems including self-injurious habits like biting and head banging, which is a typical indication of Lesch-Nyhan syndrome.
Define Lesch Nyhan Syndrome.
According to Stedman's Medical Dictionary, It is defined as follows:
Lesch Nyhan Syndrome is a disorder of purine metabolism due to deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT); characterized by hyperuricemia, uric acid renal stones, mental retardation, spasticity, choreoathetosis, and self-mutilation of fingers and lips by biting; X-linked inheritance, caused by mutation in the HPRT gene on Xq.
According to Dorland's medical dictionary, it is defined as follows:
Lesch-Nyhan syndrome an X-linked disorder of purine metabolism with physical and mental retardation, compulsive self-mutilation of fingers and lips by biting, choreoathetosis, spastic cerebral palsy, and impaired renal function, and by extremely excessive purine synthesis and consequently hyperuricemia and excessive urinary secretion of uric acid.
According to Merriam-Webster, it is defined as follows:
Lesch-Nyhan syndrome is a rare and usually fatal genetic disorder of male children that is inherited as an X-linked recessive trait and is characterized by hyperuricemia, mental retardation, spasticity, compulsive biting of the lips and fingers, and a deficiency of hypoxanthine-guanine phosphoribosyltransferase--called also Lesch-Nyhan disease.
According to Wikipedia, it is defined as follows:
Lesch-Nyhan syndrome (LNS), also known as Nyhan's syndrome, Kelley-Seegmiller syndrome and Juvenile gout, is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), produced by mutations in the HPRT gene located on (the) X chromosome.
What are the other names for the Lesch Nyhan Syndrome?
The other names for Lesch Nyhan Syndrome include:
Choreoathetosis self-mutilation syndrome
Complete HPRT deficiency
Complete hypoxanthine-guanine phosphoribosyltransferase deficiency
Deficiency of guanine phosphoribosyltransferase
hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency
Deficiency of hypoxanthine phosphoribosyltransferase
Juvenile hyperuricemia syndrome
Mental retardation syndrome
Total HPRT deficiency
Primary hyperuricemia syndrome
Total hypoxanthine-guanine phosphoribosyl transferase deficiency
X-linked uric aciduria enzyme defect
X-linked primary hyperuricemia
What are the causes of Lesch Nyhan Syndrome?
Lesch-Nyhan syndrome is an X-linked recessive disorder that is mainly inherited from the female carriers as an X-linked trait by their sons. Therefore male patients are more likely to develop this rare genetic disorder.
Lesch-Nyhan syndrome is also known to run-down in the families that presents with an abnormal production and break down of purine compounds. Purines are part of our body tissue, present in various food sources and are vital for the synthesis of our system's genetic blueprint, DNA. The syndrome is thus known to be inherited as an X-linked recessive trait. The insufficient amount of purine compound in the system retains serum uric acid levels thus resulting in serious health complications.
In addition, patients with this condition either have a missing or complete lack of an enzyme known as hypoxanthine guanine phosphoribosyltransferase 1 (HGP). This substance is vital for recycling the purine compound in the body thus resulting in an abnormal increase in the serum uric acid levels. It is believed to be caused by the complete absence of an important enzyme that modulates the uric acid level in the body.
Lesch-Nyhan disease and its sub-types are also caused by the genetic, heterogeneous mutation of the HPRT gene located on the X- chromosome. These mutations are of 400 varieties that present with the single chromosomal base substitutions, insertions, deletions, and so on. Moreover, the associated gene is situated on one of the two sex chromosomes, X chromosome. In general, males possess one X and one Y chromosome. The syndrome develops if the only one X chromosome normally present in males has an abnormal gene. In contrary, the females normally possess two X-chromosomes and the condition can occur only when both the gene copies undergo mutation. Females are more unlikely to have two copies of the mutated gene and hence males are commonly affected by the disorder.
What are the Signs and Symptoms of Lesch Nyhan Syndrome?
Lesch-Nyhan syndrome, also referred to as Kelley-Seegmiller syndrome or HPRT deficiency, is one among the rarest genetic condition that commonly affects males. Male patients often present with mental retardation, physical handicapping, and kidney problems. Self- mutilation or self- injury is a typical characteristic feature of this genetic condition. These patients develop delayed motor response accompanied by increased muscle reflexes and abnormal body movements. One can also develop tender and swollen joints due to the development of gout disease. As the disease progresses, the male patients can develop kidney damage due to massive kidney stones. Male patients present with delayed growth including puberty, and majority of them have testicular atrophy (shrunken testicles). Although, female carriers may be unaffected however they are more likely to develop gouty arthritis.
Commonly, the patients present with gout-like swelling in the joints due to an abnormal rise in uric acid levels. In some patients, bladder and kidney stones can develop. The self-destructive behavior is a striking feature of Lesch-Nyhan syndrome that includes biting lips and chewing off fingertips. However, the main cause of this abnormal behavior pattern is unknown.
Lesch-Nyhan disease can affect very young children. Some of the clinical manifestations in children include loss of voluntary muscle control, kidney stones, and a strong urge to physically hurt them-selves. However, male babies with Lesch-Nyhan syndrome may appear normal at birth and be free from symptoms. This is followed by the normal growth for the first few months and the symptoms usually predominate between 3 to 6 months of age. The first symptom of this condition can be observed by the care-takers by noticing the sand like crystals (uric acid crystals) in the diapers and the baby can present with unusual irritability.
Moreover, inability to sit up or lift up one's head is the first sign that indicates nervous system impairment. Moreover, the child may never learn to walk and one can present with abnormal, spasmodic facial muscle and limb movements (chorea) by the end of first year. In addition, an evidence of defective development of motor system can be noted by the presence of writhing motions (athetosis). At 3 years, the child can present with compulsive self-injury such as biting of the tongue, buccal tissue and lips. The self-inflictive behavior gradually increases as the disease progresses and can be triggered during stressful situations.
Moreover, the Lesch-Nyhan syndrome is generally characterized by three major clinical conditions which are as follows:
- Impairment of nervous system including neurologic dysfunction
- Disturbances in cognitive and behavioral functions accompanied with compulsive self-mutilation
- Hyperuricemia (over-production of uric acid)
Impairment of Nervous system
Developing infants commonly develop developmental delay, abnormal low muscle tone (hypotonia) during the first 3 to 6 months of age. Affected infants never walk or crawl or speak and can present with severe irritability. Abnormal involuntary muscle contractions, writhing motions (choreoathetosis), motor control (dystonia), and arching of the spine (opisthotonus) can occur due to the involvement of extrapyramidal system. Other symptoms involving the pyramidal system include overactive reflexes (hyperreflexia), spasticity, and extensor plantar reflexes. All these symptoms can force the patients to seek wheelchair support for a lifetime.
Affected patients have cognitive impairment and present with behavioral disturbances during 2 to 3 years of age. The overwhelming self-injury includes biting of the tongue, lips, fingers and head banging as the disease progresses. Around 85 percent of males develop self-harming habit which can get worse during times of stress. In addition, compulsive behavior can also develop which includes vomiting, aggressiveness, spitting, and coprolalia (involuntary swearing).
Overproduction of uric acid
Lesch-Nyhan syndrome is mainly characterized by the uric acid crystals that appear like sandy crystals in the diapers of the affected baby. Excessive abnormal production of uric acid results in the accumulation of either uric acid crystals or stones in the ureters, kidneys, or bladder. These crystals can later develop in joints resulting in tenderness and swelling eventually causing gout-like arthritis. These crystals can ultimately coalesce to form small multiple stones or prominent large stones in the urinary tract consequently causing hematuria (blood in the urine) and UTI. Untreated renal stones can cause serious complications like kidney damage.
What are the complications of Lesch Nyhan Syndrome?
Some of the complications of the Lesch-Nyhan syndrome include:
Severe, progressive disability
Renal complications, including renal failure
Hypotonia eventually resulting in death
Sudden unexpected death