Blood Test for Autism Outperforms Existing Genetic Tests

A blood test for autism spectrum disorders (ASDs) presents evidence that abnormal immunologic activity affecting brain development may help explain some of autism’s origins.

The blood test was described on December 5, 2012, in the online open access journal PLOS ONE. It is based on a large, gene-chip investigation and it could enable early diagnosis of autism in about two thirds of patients before clear symptoms start to appear at 5 years, the average age of diagnosis in the US.

Sek Won Kong, MD, of the Boston Children’s Hospital Informatics Program (CHIP; Boston, MA, USA), is the leader of a team of investigators who analyzed blood samples from 66 male patients with ASDs, and compared them with 33 age-matched boys without ASDs. They studied RNA signatures using microarrays and discovered differences in gene activity, or expression between the two groups.

Analyzing the blood samples, Dr Kong and colleagues flagged 489 genes as having distinct expression patterns in the ASD group, and narrowed this to a group of 55 genes that correctly identified or ruled out autism in 76 % of samples. They validated their findings in a second group of 104 male and female patients with ASDs and 82 controls, achieving an overall classification accuracy of 68%.

The 55 genes whose expression was altered suggest more than one path to what we know as autism. Based on their genetic signatures, subjects with ASDs clustered into four subgroups marked by changes in different biological pathways.

“It’s clear that no single mutation or even a single pathway is responsible for all cases,” said Dr Kohane. “By looking at this 55-gene signature, which can capture disruptions in multiple pathways at once, we can say with about 70 percent accuracy, ‘this child does not have autism,’ or ‘this child could be at risk,’ putting him at the head of the queue for early intervention and evaluation. And we can do it relatively inexpensively and quickly.”

Most current theories of autism focus on disordered synapses but, Dr. Kohane speculates that brain development in autism may be impaired by abnormal immune responses to infections and other stressors, during infancy or prenatally.

Boston Children’s Hospital has licensed the gene signature approach exclusively to SynapDx (Southborough, MA, USA). It can potentially diagnose autism far more often than the genetic tests currently available. Current tests look for variety of autism-related mutations but altogether, the known mutations account for fewer than 20% of autism cases.

Related Links:
Boston Children’s Hospital Informatics Program
SynapDx