Genetics and biochemistry of Lesch-Nyhan syndrome

This is a biochemical pathway chart depicting the loss of HPRT. As I explained in the biochemistry video, you can follow this pathway to see why there is an overproduction of lactic acid and why HPRT is so important. (a)


Genetics and Inheritance


History of LEsch-Nyan Syndrome

In this video I talk about the history of the genetic and biochemical research that has lead to our current Understanding of Lesch-Nyhan Syndrome. Most of the research was done in the sixties and seventies in a very efficient manner. (BTW, the Lesch-Nyhan Syndrome web site that I keep on mentioning in this video is this web site. I posted this on YouTube so...)


The other web site that I have that I mention at the end of this video is

The historical information in this video came from the OMIM web site (b)

Historical Biochemical Study on Lesch-Nyhan Syndrome

A video summarizing a historic study done in the 1960's on Lesch-Nyhan Syndrome (c)

 Just some brief clarifications, this was an early study into Lesch-Nyhan Syndrome, not the first one. Also, I have to read this article 7 or 8 times to understand the study they had done. The reason for this is that the study was one two enzymes with two different families, and information from previous was included. It was a lot of information to absorb,  but well-written.

How Does Our Study of Lesch-Nyhan Syndrome Help Us To Understand Biology in a Broader Sense?

Lesch Nyhan Syndrome in Mice?


The follow-up video

Here are the three studies that were mentioned in the video:\

Environmentally-influenced and Epigenetically Influenced Symptom Expression

The article "Mechanisms for phenotypic variation in Lesch–Nyhan disease and its variants" talked about a mutation in the HPRT gene that caused different symptoms in different individuals, despite the fact that the mutation was exactly the same. 10 individuals from 8 different families with an identical HPRT mutation were studied. A lot of variation was seen between the individuals. None of the individuals had full-blown Lesch-Nyhan Disease, instead they typically had a milder condition called HGprt-related neurologic dysfunction (HND) while one had HGprt-related hyperuricemia (HRH), the mildest of the three conditions. The age that the symptoms were expressed varied greatly, from infancy to 28 years old.

The evidence from the research seems to indicate that the reason there is a lack of HPRT enzyme activity is that the mutation causes the enzyme to experience extreme heat sensitivity. Early in development, when enzyme activity is most crucial, events such as fevers would have had particularly large impacts on the young, developing, individual.

The authors also noted that lack of protein-repair mechanisms can potentially impact enzyme activity, resulting in more severe symptoms.

Frequency of Lesch-Nyhan occurrence.

According to the NIH "The prevalence of Lesch-Nyhan syndrome is approximately 1 in 380,000 individuals. This condition occurs with a similar frequency in all populations." (d)

This is not surprising from a population genetics perspective since affected families likely have each had their own unique mutation event that lead to LND. This is due to the fact that strong environmental factors tend to prevent alleles that cause extremely harmful phenotypes from becoming common in a population. 


accessed 20 March 2013