CMAJ. 2015 Feb 3;187(2):102-107. doi: 10.1503/cmaj.140657. Epub 2014 Dec 1.

Julien L Marcadier ¹, Margaret Boland ¹, C Ronald Scott ¹, Kheirie Issa ¹, Zaining Wu ¹, Adam D McIntyre ¹, Robert A Hegele ¹, Michael T Geraghty ¹, Matthew A Lines ²

Author information

• ¹Department of Genetics (Marcadier), Children's Hospital of Eastern Ontario; Division of Gastroenterology, Hepatology and Nutrition (Boland), Children's Hospital of Eastern Ontario; Department of Pediatrics (Boland, Issa, Geraghty, Lines), University of Ottawa and Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ont.; Department of Pediatrics (Scott, Wu), University of Washington, Seattle, Wash.; Robarts Research Institute (McIntyre, Hegele), Schulich School of Medicine and Dentistry, Western University, London, Ont.; Metabolics (Geraghty, Lines), Children's Hospital of Eastern Ontario, Ottawa, Ont.
• ²Department of Genetics (Marcadier), Children's Hospital of Eastern Ontario; Division of Gastroenterology, Hepatology and Nutrition (Boland), Children's Hospital of Eastern Ontario; Department of Pediatrics (Boland, Issa, Geraghty, Lines), University of Ottawa and Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ont.; Department of Pediatrics (Scott, Wu), University of Washington, Seattle, Wash.; Robarts Research Institute (McIntyre, Hegele), Schulich School of Medicine and Dentistry, Western University, London, Ont.; Metabolics (Geraghty, Lines), Children's Hospital of Eastern Ontario, Ottawa, Ont. mlines@cheo.on.ca.

Abstract

Background: Congenital sucrase-isomaltase deficiency is a rare hereditary cause of chronic diarrhea in children. People with this condition lack the intestinal brush-border enzyme required for digestion of di- and oligosaccharides, including sucrose and isomaltose, leading to malabsorption. Although the condition is known to be highly prevalent (about 5%-10%) in several Inuit populations, the genetic basis for this has not been described. We sought to identify a common mutation for congenital sucrase-isomaltase deficiency in the Inuit population.

Methods: We sequenced the sucrase-isomaltase gene, SI, in a single Inuit proband with congenital sucrase-isomaltase deficiency who had severe fermentative diarrhea and failure to thrive. We then genotyped a further 128 anonymized Inuit controls from a variety of locales in the Canadian Arctic to assess for a possible founder effect.

Results: In the proband, we identified a novel, homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), predicted to result in complete absence of a functional protein product. This change was very common among the Inuit controls, with an observed allele frequency of 17.2% (95% confidence interval [CI] 12.6%-21.8%). The predicted Hardy-Weinberg prevalence of congenital sucrase-isomaltase deficiency in Inuit people, based on this single founder allele, is 3.0% (95% CI 1.4%-4.5%), which is comparable with previous estimates.

Interpretation: We found a common mutation, SI c.273_274delAG, to be responsible for the high prevalence of congenital sucrase-isomaltase deficiency among Inuit people. Targeted mutation testing for this allele should afford a simple and minimally invasive means of diagnosing this condition in Inuit patients with chronic diarrhea.