UNSW Embryology

Abnormal Development - Lesch-Nyhan Syndrome

© Dr Mark Hill (2008)

Acknowledgements

Lesch-Nyhan Syndrome (LNS)

Lesch-Nyhan Syndrome (LNS) was discovered over 30 years ago as an inborn error of purine metabolism by Nyhan et al (J. Pediat. 67: 257-263, 1965). Two years later, the biochemistry has been resolved by Seegmiller et al. ( Science 1967 Mar 31;155(770):1682-4).

X Chromosome - hypoxanthine-guanine phosphoribosyltransferase gene location

LNS is a rare, genetic disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase or HPRT. Many mutations have been identified in a gene on the long arm of the X chromosome in patients with Lesch-Nyhan disease. These mutations lead to a virtually complete loss of function of the enzyme HPRT.

LNS is transmitted as and X-linked recessive trait. Female carriers do not show the symptoms. LNS is characterized by self-mutilating behaviors such as lip and finger biting and/or head banging. The symptoms of LNS usually appear between the ages of 3 and 6 months.The deficiency of HPRT activity leads to accumulation of phosphoribosylpyrophosphate. The disruption of this salvage pathway in the CNS may result in cells in the brain unable to synthesize required nucleotides.

In 1996, scientists at John Hopkins showed that brains of patients with the disorder, Lesch-Nyhan disease, may have much fewer nerve endings containing dopamine, an important chemical messenger. This study also may help researchers better understand the biological causes of a major behavioral problem of the severely mentally retarded.

• NINDS Lesch-Nyhan Syndrome Information Page
• New Approaches to Understanding Lesch-Nyhan Disease
  From the New England Journal of Medicine
• Key Feature of Self-Destructive Brain Disorder Revealed
  Researchers at Johns Hopkins, using high-tech medical imaging techniques, have found the suspected fingerprint of a devastating disorder that afflicts patients
  with uncontrollable urges to hurt themselves.
• The Lesch-Nyhan Syndrome 1
  From the pedriatic database "pedbase".
• The Lesch-Nyhan Syndrome 2
  From the Online Mendelian Iheritance in Men (OMIM) databse.

Where to Next?

You should look at normal development. Development Notes

Alternatively, go on to look at Systematic Development of organs and tissues.

Quick Links

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Finally

For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

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