The Chamorros, the indigenous people of Guam, suffer from a neurodegenerative disorder known as lytico-bodig, which has a mixture of similarities to Parkinson's and Lou Gehrig's diseases, including muscle wasting, tremor, dementia and death. A 1958 survey estimated that 10% of Chamorro adults had this disease, which is about 100 times the incidence of Lou Gehrig's disease worldwide. The epidemic has greatly subsided since the 1970's.
Scientists interested in neurodegenerative disease have been going to Guam because of the high incidence of the disease and because the disease seems to be a mixture of pathologies seen in other degenerative conditions . However, despite 40 years of collecting blood samples, though, the causes of the disease have been difficult to sort out. The current consensus is that it is caused by a combination of genetic susceptibility and one or more environmental factors. The environmental insults have been variously proposed to be the cycad plant toxin BMAA , bacterial contamination in river water or magnesium deficiency.
Efforts to identify genetic factors which contribute to the disease have given mixed success. However, a advance publication to appear in PNAS is now reporting a point mutation in a calcium/magnesium channel in autopsy tissue from five patients out of 21 checked. The point mutation in TRPM7 removes a conserved phosphorylation site, and the mutant channel is thus more sensitive to magnesium inhibition. The authors propose that this channel mutation increases susceptibility to whatever environmental insult to result in the disease. The authors favor the magnesium dietary deficiency hypothesis, as it dovetails best with the defect seen in the mutant channel.
The strong point of this article is the identification of a somatic genetic alteration in a substantial fraction of lytico-bodig suffers. This point mutation is present in the public (SNP) databases, and seems to have occurred all over the world, i.e. it is not causative for the disease. However, the functional data in the paper on what this means for the channel and Ca/Mg homeostasis are really tantalizing.
In the end, the rapid disappearance of the epidemic argues against any strict genetic cause of this illness. The cycad hypothesis has received the most attention (possibly because Oliver Sacks was a co-author) and may account for the sufferers without this genetic predisposition.
I keep thinking about the human cost to these people of an epidemic of this horrifying disease, and what it must feel like for the affected families to be asked to give blood over and over again. The epidemiologist looking for mechanism might look right through the person. I have this problem generally with Sacks' writings. The NIH has been administering research into this disease since the late 50's, and hopefully there have been standards for sample sharing that are minimally onerous to the disease sufferers.