Researchers have identified a genetic mutation accountable for a metabolic disease among Inuit in northern Canada.

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Nunavik is the Northern third of the province of Quebec, Canada, and home to 19% of the total Inuit population in 2006.

The disease in question, glycogen storage disease type IIIa, is caused by mutations in the AGL gene, leading to less-active glycogen-debranching enzymes. The disorder disrupts the body’s capacity to release sugar from glycogen, resulting in the formation of damaging glycogen deposits.

Symptoms of glycogen storage disease type IIIa include hypoglycemia, enlarged liver and muscle weakness.

Glycogen storage disease IIIa affects around one in 100,000 people in North America. However, the researchers estimate that the disorder may affect around 1 in 2,500 people in Nunavik – the homeland of the Inuit in Quebec.

“The aim of our present study was to identify the genetic cause of glycogen storage disease type III in the Inuit population of Nunavik on the eastern coast of Hudson Bay,” write the authors of the study, published in CMAJ (Canadian Medical Association Journal).

For the study, the researchers conducted genetic testing on five Inuit children, all of whom had been diagnosed with glycogen storage disease type IIIa. In addition to being tested with standard DNA sequencing methods, two of the children received whole-exome DNA sequencing.

In the two children undergoing whole-exome sequencing, a mutation was reported in the AGL gene. Standard DNA testing then confirmed that the mutation was present in each of the five children. In addition, each child had an enlarged liver and hypoglycemia – symptoms of glycogen storage disease type III.

The researchers also found that five family members of the children were carriers of the mutation, with further genetic testing showing more shared genetic material. These findings are indicative of a founder effect – a loss of genetic variation occurring when a new population is formed from a small number of ancestors.

The researchers estimate that the level of glycogen storage disease type IIIa prevalence within this population is among the highest worldwide. The mutation found in the study has never before been reported in North American children, although it has been previously identified in 12 North African Jewish patients.

“This discovery will help interested families and communities receive genetic counseling and screening to help identify and manage the disease,” states study author Dr. Celia Rodd. “Early diagnosis may help prevent hypoglycemia and organ damage in infants and serious health complications.”

Targeted newborn screening among the population is one potential strategy identified by the authors for preventing newborn hypoglycemia and glycogen accumulation.

In a commentary related to the study, Dr. Jane Evans of the University of Manitoba, Winnipeg, in Canada, hails the importance of modern technology in genetic research:

Although an appreciation of such variation in disease frequency and population genetics principles has been around for some time, the application of modern methods for gene identification now has the potential to improve outcomes for patients, their families and communities.”

There are additional benefits to the discovery of a causative mutation, Dr. Evans adds: “Once a causative mutation is discovered, opportunities exist to use molecular rather than more invasive diagnostic testing, to start treatment early and to offer carrier testing to family members at risk.”

Another recent genetic study reported on by Medical News Today has given new insight to fragile X syndrome – the most common known cause of inherited intellectual disability.