Autistic children differ markedly from healthy volunteers in metabolic compounds shed in their urine, raising hopes for a biological test for the disorder that could allow doctors to catch it before behavioral symptoms show up.

While autism is largely thought of as a cluster of developmental disorders, researchers at Imperial College London found dramatic differences in the amounts of metabolites released in the urine in autistic subjects when compared against healthy volunteers as well as their non-autistic siblings, including metabolites implicated in Parkinson's disease.

The findings, published Friday in the Journal of Proteome Research, back up earlier research suggesting autistic children demonstrate abnormalities in metabolism and even bear different colonies of microbes in their guts.

"What we were able to show was that autistic children were metabolically quite different from normal children," Jeremy Nicholson, a professor at Imperial College and head author of the paper, told DOTmed News. Nicholson helped found the field of "metabolomics," the study of chemicals produced by people and the bacteria that call them home.

Intriguingly, in the study, non-autistic siblings of autistic children were not "biochemically normal," Nicholson said, with metabolic profiles landing somewhere between full-blown autistic children and healthy controls.

"Non-autistic siblings actually have some of the same biomarker differences, but much less marked, so they were enough to make them statistically different from the control group, but distinguishable from autistic brothers and sisters," Nicholson said, making it "an interesting discovery in its own right."

In the study, the researchers matched urine samples of 39 autistic children aged 3 to 9 with 34 same-aged healthy volunteers and 28 non-autistic siblings. The urine samples for autistic children, their siblings and some of their controls came from University of South Australia. A second group of control samples came from the Swiss Tropical Institute. (Although diet is presumably quite different in Switzerland and Australia, urine make-up was statistically indistinguishable, the researchers said.)

The urine was analyzed with a device known as a nuclear medicine spectrometer, and the content of urine was compared to creatinine levels in the urine to control for liquid volume.

The findings were curious. Autistic children showed lower levels of the compounds hippurate and PAG, byproducts of digestion produced by gut microbes. PAG comes from the breakdown of proteins by gut flora known to help their hosts extract energy from food. Autistic children also have decreased levels of glutamate in their urine, also associated with energy metabolism, Nicholson said.

"Glutamate is important in protein building and as an energy source," he noted.

Autistic children are known to have a different composition of gut flora, the microbes inhabiting our intestines, with around eight species of Clostridia bacteria not found in most children, Nicholson said.

Clostridal bacteria include some "nasty ones," he added, such as C.difficile, a hard-to-kill bug responsible for many hospital-acquired infections, as well as the germ that produces botulinum, a powerful neurotoxin. But there's no evidence for a causal relationship with autism: it's just as likely some autistic children have behaviors, diets or changes to the immune system that result in unusual populations of gut microbes.

The compounds showing the greatest (and only reliable statistical) difference between autistic subjects and controls were with succinate, involved in amino acid metabolism, and byproducts of metabolizing nicotinic acid. High excretion of one of these products, NMND, is also implicated in Parkinson's disease. A structurally similar byproduct found in badly made street heroin causes a Parkinson's-like condition in street addicts, Nicholson said.

Also, large amounts of taurine were shed in the urine of some, but not all, autistic subjects. Taurine, a sulfur-containing, non-protein-building amino acid, helps create the bile acids involved in breaking down fat in the gut.

"We know in liver diseases you get taurine in the urine," Nicholson said. Earlier research has pointed to sulfur metabolism problems in autistic children.

But the study in many ways raises more questions than it answers, and it's still too early to tell if a urine test really could reliably help diagnose autistic children, or at least a subset of them.

"We need a more detailed study," Nicholson said.

But if it works it could help push back the age at diagnosis, which is important, because earlier treatment is usually the most successful, Nicholson said. Right now, most autistic children are diagnosed between 18 months and two years of age, he said.

About 30 percent of autistic children in the study had gastrointestinal disorders, Nicholson said. At a Pediatric Academic Societies meeting in Vancouver earlier this month, researchers reported around 45 percent of autistic patients had GI troubles, although the evidence for GI disorders in those with autism has been controversial.

The children with GI disorders did not form a separate cluster in the statistical analysis, Nicholson said, meaning they didn't seem more likely to shed unusual quantities of chemicals in their urine.

In the study, autistic children were all diagnosed with full autism using the DSM-IV, the standard psychological manual for diagnoses. Nicholson said those with Asperger's, or milder versions of the disorder, were excluded.

"Asperger's is diagnosed much later, usually when they're teenagers," Nicholson said. "They're metabolically very different, fully sexually mature, with changes in hormones." There might be a separate set of biomarkers for that condition, he noted.

For a follow-up study, he wants to enroll more children and check them every day, or week, to get a better picture of their metabolic profile. Controlling the children's diet -- to ensure supplements or foods weren't interfering with the results -- while possibly hard to pull off, would also help bolster the findings.

The incidence of autistic spectrum disorders has nearly doubled over the last 30 years, from one out of 1,000 in 1980 to one out of 500 now, according to the Annual Review of Public Health, although no one is sure if the increase is caused simply by changes in how diagnoses are made.

Nicholson suspects that ultimately the cause for autism spectrum disorders will be a gene-environment interaction that affects development.

"Probably, we can only really solve the problems associated with autism by stepping back and looking at the whole mosaic and finding which bits of the pattern are really important," he said.