Timeline of Syndrome
Symptoms
- Infants will have "orange sand" in diapers
- Symptoms become evident between 3-6 months
- Urine may be pink or reddish in color (hematuria)
Healed scars on Lesch-Nyhan patient as a result of self-biting
- Involuntary movements begin between 6 - 18 months
- Patient may develop kidney stones or kidney failure
Lesch-Nyhan patient with head protection and no teeth
- Due to muscle weakness (hypotonia), patient may be slow at learning how to crawl, roll over, or sit and may never learn to walk
- Behavioral problems and self-injury not usually present until after the 2nd birthday
- On average, most die in their 20s or 30s
- Weak muscles affect ability to eat and swallow which can lead to aspirating food into the lungs, causing aspiration pneumonia
Treatment
- Usually treated with medication called allopurinol, urine alkalinization, and hydration
- Physical rehibilitation for management of muscle weakness
- Behavior problems may include abnormal involuntary movement, self-mutilation, and complusive behaviors
- No treatment for neurological and behavioral symptoms
Lesch-Nyhan patient with custom helmet and limited motion elbow orthoses
- Self-injury requires restraints and in some cases surgical extraction of teeth to prevent patient from harming himself
- Irritability and uncontrolled aggressive behavior
The Science Behind It Cont.
- Formation of DNA - nucleotides
The Science Behind It Cont.
- Nucleotides synthesized from amino acids
- In absence of HGPRT, purine bases degrade and are excreted as uric acid, as well as the synthetic rate for purines is accelerated
- HGPRT is the "salvage enzyme" for the purines
- Increased production of uric acid = hyperuricemia
Bibliography
- Failure of HGPRT enzyme results in cell breakdown products not being reused and therefore degraded. This increases uric acid and a purine breakdown product
- Hyperuricemia: Excess of uric acid in the blood
- Inflammatory reaction and gouty arthritis
- Urate stones, hematuria, and UTIs
What is Lesch-Nyhan Syndrome?
Kale, A., K. Shah, and S. Hallikerimath. "Lesch-Nyhan Syndrome: A Case Report." Journal of Indian Society of Pedodontics and Preventative Dentistry. Wolters Kluwer - Medknow, 1 May 2005. Web. 3 June 2015.
The Science Behind It
- LNS is an X-linked recessive disorder, caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and produced by mutation in HGPRT gene
A rare X-linked recessive condition in which there is complete absense of activity from the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT).
- HGPRT enzyme present in each cell in body but highest concentration is in the basal ganglia part of the brain
"Madisons Foundation - Moms And Dads In Search Of Needed Support." Madisons Foundation. Madisons Foundation, 31 Aug. 2003. Web. 3 June 2015.
- Basal ganglia is thought to be the director of which of the potential actions the cortex might be planning gets executed. May also play a role in planning and coordinating specific movement sequences
Who Does it Effect?
- Males have the disease and females are carriers
How is it Caused?
- HGPRT gene localized on the long arm of the X chromosome
- If mother is carries, 50/50 chance that sons will have disease and 50/50 chance that daughters will be carriers
Denny, Dallas. "Self-Injurious Behavior In Lesch-Nyhan Syndrome (1985)." Dallas Denny Body of Work. George Peabody College of Vanderbilt University, 1985. Web. 3 June 2015.
- The lack of HPRT activity results in an overproduction of uric acid
Diagnosis
- Distributed evenly between races and geographic locations
- Occurs as frequently as 1 in every 380,000 births
- LNS can be diagnosed based on symptoms described
- Most commonly inherited in an X-linked recessive pattern from carrier mother
- Blood and/or urine tests to look for elevated levels of uric acid
- Can occur from spontaneous genetic mutation
- 1/3 of cases are spontaneous
Palermo, Elizabeth. "What Is Uric Acid?" LiveScience. TechMedia Network, 26 Apr. 2014. Web. 3 June 2015.
- HPRT enzyme action in blood and/or cells is tested
- Molecular genetic testing
- Prenatal diagnosis possible if history of this mutation in the family
Garcia Puig, Dr. Juan, and Dr. Rosa Torres Jimenez. "Lesch-Nyhan Syndrome." Orphanet. Orphanet, 1 Apr. 2010. Web. 3 June 2015.
- Other diagnosis: cerebral palsy, autism, Tourette syndrome, Cornelia de Lange syndrome, idiopathic intellectual deficit, and severe psychiatric disorders
"Lesch-Nyhan Syndrome." Genetics Home Reference. Genetic Home Reference, 1 Feb. 2013. Web. 3 June 2015.
Chhabra, Namrata. "Case Study-Lesch- Nyhan Syndrome." Biochemistry for Medics. 19 Mar. 2012. Web. 4 June 2015.
Lesch-Nyhan Syndrome