A NEW DIRECTION: Hannah Poling, pictured above with her father Jon, revealed a possible underlying cause of autism that many outside the scientific community were unaware existed. Image: AP PHOTO/W.A.HAREWOOD
When the parents of Hannah Poling, a nine-year-old, Athens, Ga., girl who was diagnosed with autism just after the age of two, announced that a federal vaccine injury court had awarded them a settlement, the case reignited a decade-old debate about whether vaccines could potentially trigger the disorder. But what was somewhat lost in much of the coverage of the case was a little-known condition that the court said was aggravated by the vaccine, and which gave Hannah the features of autism.
That little known condition—"mitochondrial disorder"—involves the parts of cells frequently referred to as their "power plants," because they turn sugar into energy. Mitochondria are found in all tissues and organs in the body, and when they do not work properly they can cause or worsen diseases from diabetes to brain disorders. Jay Gargus, a specialist in human genetics and metabolism at the University of California, Irvine, says mitochondrial disorders are a bit like an electrical brownout: "As the electrical voltage starts falling, different appliances will start to fail," he says. "First, the television might turn off, then the lights might go off."
In July 2000, at 19 months of age, Poling received five vaccines containing nine immunizations—including inoculations against rubella (German measles), mumps and chicken pox. The girl had been developing normally, according to her parents—her father, Jon, is a Johns Hopkins–trained, practicing neurologist, her mother is an attorney and registered nurse—but in the months after the shots, she developed a fever and litany of other symptoms: diarrhea, appetite loss and intermittent screaming. A pediatric neurologist examining her in February 2001 later noted that she had lost some of the speech she had previously acquired, was no longer making eye contact, and was no longer sleeping through the night.
In its November 2007 decision the vaccine court said that the inoculations Poling received in July 2000 worsened her underlying mitochondrial disorder (which was discovered nearly a year later) and led to brain disease that appeared as symptoms of autism.
Theoretically, that makes sense: David Holtzman, a pediatric neurologist at Massachusetts General Hospital in Boston, notes that the brain is particularly dependent on the energy supplied by the mitochondria. "What's surprising and hard to specifically understand is why it's so characteristically affecting language function and social function," he adds. (In addition to symptoms of autism, Poling also reportedly had muscle weakness, difficulty with motor coordination, and a host of gastrointestinal problems.)
So how common are mitochondrial disorders? Could they explain why some children who receive vaccines develop autism, but the vast majority do not?
In an opinion piece in The Atlanta Journal-Constitution, Poling's father cited a 2005 study by a Portuguese research team that estimates as many as one in five kids diagnosed with autism also have a mitochondrial disorders. He notes that such a rate "does not qualify as 'rare.' In fact, mitochondrial dysfunction may be the most common medical condition associated with autism."
Hannah's disorder is likely due to a rare mutation in her DNA. Most of the DNA responsible for mitochondria is inherited from mothers, because mitochondrial genes are carried in the egg but not sperm. Salvatore DiMauro, a mitochondria expert at Columbia University, notes that the point mutation mentioned in Poling's case history--published in the Journal of Child Neurology--would imply that both she and her mother carried the genetic variation in all their tissues. So, he says, "you would expect to see the same results" in both the mother and the daughter. But Poling's mother, Terry, who is an attorney and a registered nurse, is not autistic.
That suggests the genetic defect responsible for Poling's condition is part of her nuclear DNA, which is separate from the mitochondrial variety, says DiMauro. This means that, scientifically, from the documents presented in the vaccine court, the Polings did not make a case that deserved compensation. (Attempts to contact Jon Poling about DiMauro's concern went unanswered; however, he agreed that his daughter's causative genetic defect was likely not in her mitochondrial DNA in an open letter on the blog NeuroLogica.)
John Shoffner, a mitochondrial disease expert who runs a laboratory in Atlanta, agrees. In at study of 40 patients with autism—including Poling, he found that two thirds had muscle weakness. If muscle weakness is seen early on in children, it may be a tip-off to an underlying mitochondrial disorder that could cause autism, because muscles are heavily dependent on mitochondria as an energy source. He also believes that the new work—he presented preliminary results last week at the American Academy of Neurology Conference in Chicago—will help explain why some children, such as Poling, experience worsening symptoms as a result of a fever.
He notes that the route from the vaccine to the child's autism was by no means direct. Hannah's mitochondria were already underperforming, so when she developed a fever from her vaccine, the increased energy requirements likely pushed them past their thresholds. A fever caused by an ear infection or the flu would likely have triggered the autism symptoms if they occurred before or between the ages of 24 and 36 months, he says, which is when classic, regressive autism, which affects one third of sufferers, usually appears.
Shoffner notes that parents and advocates looking to impugn vaccines as triggers for autism—or mitochondrial disease—need direct, not just circumstantial, evidence. "If you were sitting in a waiting room full of people and one person suddenly fell ill or died or something," he says, "would you arrest the person sitting right next to them?"