Abstract
In an effort to further understand the pathogenesis of Lesch-Nyhan syndrome, an X-linked
recessive disease of purine metabolism associated with a deficiency of hypoxanthineguanine
phosphoribosyltransferase, we have analyzed the amino acids in autopsy brain material
obtained from five patients and six controls. The amino acids glycine and glutamine
serve as substrates for the synthesis of purines in man.
Amino acids were measured in the occipital cortex, limbic cortical area, cerebellar
cortex, hippocampus and putamen. In general the amino acids were usually lower in
concentration in brain material from affected individuals. Most dramatically decreased
were threonine, serine, valine, isoleucine, lysine and arginine. Only glutamine and
urea were higher than controls. Glutamate, gamma-aminobutyrate and cystathionine were
essentially unaffected.
The data reported here do not support a role for increased glycine in the pathogenesis
of this disease as implied by findings previously reported in cultured cell lines
(Skaper and Seegmiller 1976, 1977). The current findings suggest that individuals
with Lesch-Nyhan syndrome have a generally lower concentration of free amino acids
in brain. This decrease may be involved in the etiology of the disease or the decrease
may be a result of the generally malnourished state of these individuals. These results
imply that affected patients have a limited supply of amino acid precursors available
for the synthesis of either proteins or neurotransmitters that the brain requires
for normal function. Thus, the low amino acid pools could be an important factor in
the brain dysfunction observed in patients with Lesch-Nyhan syndrome.
Key words
Lesch-Nyhan syndrome - HGPRT deficiency - Brain amino acids - Glycine - Glutamine
- Decreased amino acid content
