Lesch-Nyhan Disease

Self-mutilation is a Major Sign of Lesch-Nyhan Disease

Humans are remarkably different from other species in this universe as they are blessed with thinking abilities. People worldwide follow different traditions, cultural practices and eating habits as per their upbringing. During early ages man hunted animals for food and survival, started farming for growing crops, ate the different produce and grains he/she reaped advancing to our present eating habits. Eating insects became popular sometime back and people now eat everything from ants, crickets and cockroaches to beetles and bugs. Get an idea on the most-popular insects preferred by people worldwide from the website www.firsteatright.com. Even cannibalism was practiced during early centuries as a means of self-defense, occult culture, revenge or during famine. While cannibalism is the act of eating another human’s flesh and organs, there are a strange few who love to eat their own flesh and body parts! It does sound weird, horrifying and terrorizing but its true.
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Lesch-Nyhan Syndrome
A type of rare disease, Lesch-Nyhan syndrome is characterized by the deficiency/absence of the activity of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). We call it rare because only 1 person of every 3,80,000 people are affected by this disease and rarely these individuals live past their 40th birthday. Hypoxanthine and guanine are purines (nitrogen-containing compounds found in foods such as meat and poultry) and the absence of the HPRT enzyme prevents these purines from building into nucleotides. Further, they are degraded and excreted as uric acid which accounts for unusually high uric acid levels in people with this syndrome.

Gene Inheritance
Lesch-Nyhan disease predominantly strikes the male gender (85%) and is inherited in an X-linked recessive manner. X chromosomes is one of the two sex chromosomes. Females have two X chromosomes and males have one X and one Y chromosome. Females who have one mutant copy of the gene do not have the diseases but are called as carriers as they have one copy of the gene responsible for the disease. The female carrier possess a 25% chance to give birth to a carrier daughter just like herself, a 25% chance of giving birth to a non-carrier daughter, a 25% chance of giving birth to a son who has the disease and a 25% chance to give birth to a perfectly normal son. Males with one mutant copy of the responsible gene show signs and symptoms of the syndrome as they don’t have another X chromosome with a normal working gene as present in the female population. That’s the primary reason why X-linked recessive disorders such as Lesch-Nyhan syndrome mostly strike the male population. Such affected males will surely pass this disease onto their daughters (all of them) as the dad always passes the X chromosome to his girl child who then becomes a carrier of the gene. Likewise, a male can never pass over this disease to his son as it is always the Y chromosome that the father passes onto his son. The only gene associated with Lesch-Nyhan syndrome is located on the X chromosome and called as HPRT1.

Signs & Symptoms
Neurological and behavioral abnormalities and overproduction of uric acid are the three-most common characteristics of this disease. Different symptoms occur due to this disease at different stages of life.

During Infancy/Childhood

1. Symptoms might appear as early as six months of age in the form of orange crystals/sand in the diapers of the infants with this disorder but are rarely diagnosed during this stage. The orange coloration is due to abnormally high levels of uric acid in the urine.
2. Excess uric acid released as sodium urate lead to urate stones developing in the kidneys of infants with Lesch-Nyhan syndrome
3. Urate stones might lead to blood in the urine or urinary tract infection too
4. Neurological symptoms start before an infant completes 12 months which include involuntary writhing movements of the arms and legs, repetitive movements such as flexing the fingers, raising/lowering shoulders and scowling face expressions.
5. Infants fail to reach developmental milestones such as crawling, sitting or walking. Even those infants who could sit upright lose their ability to do so as they grow
6. Affected infants experience increased muscle tone and muscle rigidity
7. Mental retardation is seen rarely but in general, IQ level is lesser compared to other infants due to poor speech
8. The most important symptom observed in almost 85% patients is self-mutilation which begins between the ages of two and three. This can also begin as early as the child’s first birthday or even during childhood. Typical symptoms include repeated biting of the lips, fingers, hands and nails that lead to constant loss of tissue and repeated banging of the head against some hard object. Aggressiveness, vomiting, spitting, face scratching, screaming, irritation and difficulty in swallowing are also observed in the affected children.
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Teenage/Adulthood

1. Urate crystals can be present in joints and it is not until teenage or adulthood that untreated patients experience constant pain and swelling of the joints. Once these start, such individuals face frequent episodes of these symptoms.
2. Severe muscle spasms occur that causes the back muscle to arch and the head and heels to bend backward.
3. Affected children/teens may also be affected by hip dislocation, fractures, abnormal curvature of the spine or joint abnormalities
4. Female patients don’t have much of any of these symptoms but may develop gout later in life due to excess uric acid in the blood.

Diagnosis
The physician usually requests for a detailed patient history and specialized blood tests. Genetic testing for the HPRT1 gene can also determine the specific disease-causing mutation. Carrier testing and prenatal diagnosis is also possible.

Treatment
Treatment depends on the symptoms exhibited. It might require the combined effort of a team of pediatricians, orthopedics, physical therapists and other health care professionals to understand and plan the child’s treatment procedure.

No definite treatment plan/drug is said to be helpful in treating neurological problems and there is minimal positive effect found in reducing self-mutilation rates with the help of behavior-modification techniques. The self-mutilation behavior might decrease or even stop as the adult reaches adulthood. Certain drugs do ease pain to a certain extent. Genetic counselling might work for families who have children with Lesch-Nyhan syndrome. Affected individuals mostly don’t survive past their first or second decade of life due to renal failure.