Learn: Understanding Lesch-Nyhan

This website was created by parents who have experienced what you are currently going through.  We also collaborated closely with medical experts in their respective fields along the way.

We vividly recall the emotional impact of receiving such a diagnosis and the apprehension associated with navigating the uncertainties ahead. The overwhelming sense of grief can be immobilizing.

Relying on the families and community who have been through this, we have compiled resources to help answer any immediate questions you may have.

The following information is comprehensive and may feel overwhelming. We encourage you to take it one step at a time. Remember, Lesch-Nyhan Syndrome (LNS) is a spectrum and not every child experiences every symptom. Most importantly, we want you to know you are not alone and you will get through this. We are here to help in any way we can.

Understanding Lesch-Nyhan Syndrome

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Signs and Symptoms

Research and Development

Glossary of Terms

Basic Overview

Lesch-Nyhan Syndrome is an uncommon genetic condition caused by a small error in the body's genetic code. This error leads to a lack of a crucial enzyme, which affects how the body handles certain substances. People with Lesch-Nyhan Syndrome may experience an increase in uric acid levels, potentially leading to kidney-related issues. They might also face challenges related to movement and behavior, such as difficulty controlling movements or a tendency towards self-harming actions. This condition is unique and multifaceted, requiring thoughtful and dedicated care for those living with it.

In-Depth Medical Perspective

Lesch-Nyhan Syndrome is a complex motor-behavioral condition that results from mutations in the gene coding for the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT), that results in increase in production of uric acid and hyperuricemia. There are two classes of LNS: Classic and Variants. Here's a more detailed breakdown on the difference between Classic LNS and LNS Variants:

  1. Classic Lesch-Nyhan Syndrome: This form is characterized by self-harmful behaviors, neurological disability, and overproduction of uric acid. These patients typically display the full range of symptoms associated with LNS.

  2. Lesch-Nyhan Variants (LNV): This category is more nuanced. It includes:

    • Individuals with neurological symptoms (which can vary in severity) but without the behavioral issues like direct self-harm.

    • Individuals with only high uric acid levels and no significant neurological or behavioral symptoms. This is also known as HPRT-related hyperuricemia (HRH).

The assessment of HPRT (hypoxanthine-guanine phosphoribosyltransferase) enzyme activity was a key diagnostic tool in the past. Measuring HPRT activity helped in differentiating between the classic form of LNS and its variants. However, it's important to note that diagnosis and understanding of the disease have evolved with advances in genetic testing and a deeper understanding of the condition's clinical spectrum.

The distinction between classic LNS and its variants is based not only on the presence or absence of specific symptoms but also on their severity and combination.

Lesch-Nyhan Syndrome is like many other illnesses where the symptoms and how bad they are can differ from person to person. Just like there are different shades of a color, there are different types (or "phenotypes") of this disease that determine what symptoms someone might have and how severe they might be.

While living with Lesch-Nyhan Syndrome presents its unique challenges, it's important to remember that children with this condition can lead joyful lives. These special children possess the wonderful ability to laugh, smile, and enjoy the world around them. They form meaningful friendships and participate in playful activities, sometimes with a bit of extra support or in their own unique way. Their experiences may be different, but they are full of life, capable of happiness, and have endless potential for creating beautiful moments. Every child with Lesch-Nyhan Syndrome brings their own special light to the world, teaching us about strength, resilience, and the power of an optimistic spirit. In their journey, they remind us that happiness and love know no bounds.

The three major clinical symptoms of Lesch-Nyhan Syndrome  are:

  • Overproduction of uric acid

  • Neurologic disability

  • Behavioral problems

The characteristic evolution of motor involvement is:

  • 3-6 months: Hypotonia

  • 6-24 months: Involuntary movements (predominantly dystonia)

  • 24-48 months: Self injury and oppositional behavior

Three phenotypes are recognized in the spectrum of HPRT1 disorders: Lesch-Nyhan Syndrome  at the most severe end, the intermediate phenotype HPRT1-related neurologic dysfunction (HND). and HPRT1-related hyperuricemia (HRH) at the milder end of the continuum. HPRT activity and genotype has significant correlation with the severity of the neurological disease.

There are more than 2,000 gene variants (mutations) reported and affects 1: 235,000 to 380,000 newborn males.

X linked disorder. If the mother of the proband has an HPRTI variant, the chance of transmitting it in each pregnancy is 50%: males who inherit a pathogenic HPRT1 variant will be affected, females who inherit the pathogenic variant will be carriers.