Sugar intolerance in northern populations linked to specific gene, researchers say

For some northerners, there is reason to cut down on sugar that has nothing to do with New Year's resolutions: A genetic intolerance to sugar is hardwired into the DNA of some Arctic peoples.

A newly identified gene in the Canadian Inuit population is responsible for a condition that makes it difficult or even impossible for the body to digest sugar.

The condition, congenital sucrase-ismaltase deficiency, or CSID, affects only 0.2 percent of North Americans of European ancestry, but has a much higher prevalence among people indigenous to the far north.

Now a team of Canadian and U.S. medical researchers has pinpointed the genetic mutation that is responsible for the disorder among at least one northern indigenous population.

The study, published in December in the Canadian Medical Association Journal, estimates that prevalence of CSID -- with a matched pair of genes carrying the Inuit-specific mutation -- is 3 percent among the Canadian Inuit population studied. An estimated 28.5 percent of people in that population are considered carriers of CSID, having at least one of the recessive genes, according to the study findings.

The genetic prevalence is believed to be similar in northern coastal Alaska Native populations, which are related to the Canadian Inuit, said co-author Dr. Ronald Scott, a professor of pediatrics and genetics expert at the University of Washington.

Less certain is the prevalence outside of North America. In Greenland, it's estimated that 5 percent to 10 percent of the Inuit residents have CSID, but that is based on dietary experiences, not solid data. There is no data yet about Siberian Natives, Scott said.


Awareness, said Scott, is "practically nonexistent."

"It's unusual, and it's a rare disorder, except it's not rare in the circumpolar population," he said.

The study, led by researchers with the Children's Hospital of Eastern Ontario, was prompted by a dire case suffered by a newborn girl from Canada's Baffin Island. Five days after her birth last spring, the baby was hospitalized with what was suspected to be a case of pneumonia. Her condition improved, but once she was fed formula, she developed copious watery diarrhea -- a potentially grave condition for infants because it can lead to failure to thrive, or worse.

It turned out her health problems were caused by the sugar in the infant formula she was eating. The baby recovered once she was put on a diet of carbohydrate-free formula, and was thriving at last report, the study said.

The prevalence and carrier calculations in the study were based on genetic analysis of 128 healthy Inuit individuals living in various parts of Arctic Canada.

As with the Baffin Island baby, the remedy for older children with the disorder is simple: a traditional Native diet, or any other diet that is free of sucrose.

"One of the main points of the paper was to raise awareness that CSID is common, treatable, and can be misdiagnosed as a number of other common conditions, including irritable bowel syndrome," Dr. Matthew Lines of the Children's Hospital of Eastern Ontario and a co-author of the study, said in an email.

How long the gene has existed in the Inuit population, and how it developed, is yet unknown, Lines said. For people following a traditional, low-carbohydrate diet, inability to digest sucrose was a non-issue and likely went unnoticed until the sugary Western diet was introduced, he said.

"In general, there are a few ways that a gene change can become common in a population: It can be common among the original founders of the population, it can increase randomly over time via 'genetic drift,' or it can be an adaptation through natural selection. Sorting out which is the case would require additional studies that were not part of our paper."

There is evidence that carriers of a single CSID gene, even though it is recessive, can have a milder form of sucrose intolerance, but that physical process has yet to be fully studied or understood, the study notes.

Elevated CSID rates have been seen in some non-Inuit Native populations as far south as Manitoba, Lines said. But the condition is not believed to be particularly prevalent among interior Natives, like the Athabascan, he and Scott said.

Signs of CSID usually do not emerge until babies start eating solid food, experts say.

Breast milk has lactose rather than sucrose, and CSID-affected infants can process lactose without any problem, Lines said. Many infant formulas also lack the type of sugars that would cause the CSID symptoms, he said.

Once symptoms occur, the severity is related to diet, though there are wide variations among individuals, experts say.

"Kids who are in real trouble with this are on the Cheetos-and-Coca-Cola diet," said Dr. Matthew Hirschfeld, director of maternal child health at the Alaska Native Medical Center.

The specific culprit is sucrose -- a combination of fructose and glucose, and also known as table sugar. Not all sugars are chemically equal, so not all sugars or sweet foods cause problems. For example, Hirschfeld said, fruit juice, with no added sugar, is digested without problem because its sugar is fructose alone.

Nonetheless, CSID symptoms can arise from surprising dietary sources, he said. Sometimes infant formula that is marketed otherwise has sucrose slipped in, possibly inadvertently, he said. Sucrose, contained in corn syrup, is ubiquitous in processed and packaged foods, he said.


For children and adults with serious digestive distress, a new test developed by Scott makes it easier to determine whether the problems are caused by CSID.

The blood test, made available last year, and an outgrowth of the research that identified the Arctic gene associated with CSID, is far easier, less invasive and less expensive than the old way of testing for the disorder -- which was an intestinal biopsy that required hospitalization, sedation and a tube inserted through the digestive system to snip off a tissue sample. Testing of blood samples, with analysis done at Scott's laboratory at the University of Washington, costs hundreds of dollars, compared to the thousands of dollars that were needed to pay for each intestinal biopsy.

Hirschfeld, who makes quarterly trips to Nome to treat children there, said he has seen about a half-dozen cases in the past six months that were serious enough to warrant the test. All came back positive for the gene, he said.

Expect more such diagnoses, he said. "As the new blood test is coming out, we're going to see more and more kids testing positive for this," he said.

If affected children or adults want to indulge in sugary treats, there is an option allowing that: use of a prescription drug that supplies the missing enzymes.

The drug, Sucraid, is analogous to Lactaid, a medicine used by people with intolerance to the lactose in milk products.

But the Sucraid option can be expensive. Costs for a month's supply can run up to about $2,000, Hirschfeld said.

Those costs are not currently covered by Medicaid. In October of 2011, manufacturer QOL Medical voluntarily dropped out of the federal Medicaid drug rebate program, said Chad Hope, pharmacy program manager for the Alaska Division of Health Care Services.

Yereth Rosen

Yereth Rosen was a reporter for Alaska Dispatch News.