Insufficient intestinal enzyme activity can result in symptoms such as bloating, abdominal pain, and chronic diarrhea as maldigested carbohydrates pass into the large intestine causing an osmotic load, bacterial fermentation, and accelerated transit (Treem, 1995). The historical “gold standard” for diagnosing CSID is via a disaccharidase activity assay from an invasive small bowel biopsy tissue sample (Heitlinger, Rossi, Lee, & Lebenthal, 1991; Treem, 1995). A CSID diagnosis is historically defined as an absent or very low level of sucrase-isomaltase enzyme activity with normal small bowel tissue histology and normal lactase activity. Without more explicit diagnostic tools, the exclusion of patients with abnormal morphology and/or reduced lactase activity could result in false negatives (Lebenthal, Rossi, Nord, & Branski, 1981). Therefore, a more specific genetic test for CSID would provide an inexpensive, noninvasive diagnostic clinical tool.
Currently, CSID is identified as an autosomal recessive genetic disorder (Antonowicz, Lloyd-Still, Khaw, & Shwachman, 1972) noted by Naim and colleagues to be located in the sucrase-isomaltase gene (Sander et al., 2006), and, to date, as many as 27 mutations have been discovered (Uhrich, Wu, Huang, & Scott, 2011). In 31 previously diagnosed CSID patients, sequencing all exons of the SI gene revealed approximately 80% to be variant homozygous or compound heterozygous while the rest of the patients were true heterozygotes (Uhrich et al., 2011). Accordingly, the emerging evidence suggests that certain CSID may be inherited in an autosomal dominant manner.
Sucrase-isomaltase deficiency has not been adequately studied as a potential cause for the clinical symptoms of chronic idiopathic diarrhea and chronic abdominal pain in the pediatric population. Therefore, this study will assess whether a simple, inexpensive screening tool in the form of a genetic test and a 13C-sucrose breath test can be used to rule out a rare disease called congenital sucrase-isomaltase deficiency (CSID).
Approximately 2,000 people 18 years of age or younger will take part in this study at approximately 20 different hospitals and medical facilities across the United States. Participation could last up to 8 weeks with a potential for 3 doctor’s office visits. The length may be shorter than 8 weeks if criteria for the next visit are not met.
Those subjects with common CSID variants, along with 30 subjects without common CSID variants (controls), will return for a second doctor’s office visit for a 3-hour 13C-sucrose breath test to assess functional sucrase activity. The 13C-sucrose breath test results will be available once processed, but the genetic results will remain blind to investigators and the subject/parent(s) until the completion of the study.