Research Highlights

Potential treatment for rare group of childhood brain disorders

Published online 29 August 2013

Sara Osman

Purines are a group of nucleotides that include ATP and GTP — molecules that form the building blocks of DNA — and transport energy in cells. The cells can synthesise GTP from scratch, or make it by recycling bits of broken down purines.

An international team of researchers from the United States, Egypt, Saudi Arabia and Turkey found a link between mutations in the gene that codes for the enzyme AMPD2, which is involved in regulating de novo biosynthesis of purines, and a group of childhood neurodegenerative diseases known as pontocerebellar hypoplasia (PCH), publishing their results in Cell1. In PCH, the brainstem and lower parts of the brain are shrunken, resulting in cerebral palsy and mental impairment.

The team compared the genomes of 30 PCH patients to 1500 people living in the Middle East, and found that the AMPD2 gene was mutated in 5 PCH patients. They then inserted mutated forms of the gene into AMPD-knockout yeast, and could not detect AMPD activity, suggesting the mutations rendered AMPD2 dysfunctional.

There were lower levels of GTP when AMPD2 was missing, resulting in the faulty production of proteins, causing neurodegeneration. By administering purine precursors to either the knockout yeast or the PCH patients' stem cells, GTP levels and protein synthesis were restored. This suggests that administering de novo purine precursors may be a potential cure for the so far incurable PCH.


  1. Akizu, N. etal. AMPD2 Regulates GTP Synthesis and Is Mutated in a Potentially Treatable Neurodegenerative Brainstem Disorder. Cell (2013) doi:10.1016/j.cell.2013.07.005