Patients with Lesch-Nyhan Syndrome Have Biochemically Altered Skin, Urine, and Spinal Fluid

According to News Medical, a recent international study designed to understand Lesch-Nyhan syndrome and its potential treatments discovered something intriguing: biochemical changes in the skin, cerebrospinal fluid, and urine. Now, researchers seek to understand how this can be harnessed for treatment. Check out the full study findings in PNAS.

Lesch-Nyhan Syndrome

According to the Genetic and Rare Disease Information Center (GARD), Lesch-Nyhan syndrome, sometimes referred to as Lesch-Nyhan disease, is:

a condition characterized by neurological and behavioral abnormalities and the overproduction of uric acid in the body [which] occurs almost exclusively in males.

In general, it mostly impacts males because it is an X-linked recessive genetic disorder. In this case, the genetic mutation occurs in the HPRT1 gene. Only 1 in every 380,000 infants will inherit Lesch-Nyhan syndrome.

In addition to a build up of uric acid, those with Lesch-Nyhan syndrome also experience sodium urate accumulation in the joints and kidneys. Symptom onset can occur as early as six months. These include:

  • Gout
  • Kidney and bladder stones
  • Bloody urine
  • Urinary tract infections
  • Bulges in the ear
  • Anemia
  • Involuntary muscle movements
  • “Floppy” muscle tone in infants
  • Developmental delays
  • Moderate cognitive or intellectual delays
  • Self-harming behaviors (which occur in around 85% of patients)

Learn more about Lesch-Nyhan syndrome.

Recent Study

Prior Findings

Those with Lesch-Nyhan syndrome often lack an enzyme called HGprt, which regulates purine nucleotide metabolism. What are purines? Well, they’re part of DNA and RNA structures.

Usually, researchers test nucleotide levels in cell cultures. But there were never any abnormalities in cultures of Lesch-Nyhan syndrome. However, researchers discovered that biochemical changes couldn’t be seen in these cultures because of folic acid.

You may know folic acid as vitamin B9. It has a lot of uses: making DNA, strengthening skin and nail health, supporting prenatal health and fetal development. Additionally, cell cultures use extremely high levels of folic acid, up to 100x more than is naturally found in the blood. According to researcher José Manuel López:

“This is for cells to divide and grow faster, but it does not reproduce what happens [naturally] in the body.”

Changing Folic Acid Levels to Study Lesch-Nyhan Syndrome

In this most recent study, researchers examined Lesch-Nyhan cells using cultures with a natural level of folic acid. As a result, they found that biochemical changes caused by this condition include:

  • Lower levels of ATP, a purine nucleotide used for energy
  • Higher levels of ZMP, a potentially toxic substance
  • Increased derivatives of ZMP in the urine and cerebrospinal fluid

However, their findings also suggest that folic acid could be used as a potential treatment. As high levels of folic acid in the cultures reversed these changes, using it to treat patients could see beneficial reactions.


Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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