Breath tests: Are we ready for point of care testing yet?
Brett Hoskins, DO1, Steven Miller, MD1, Ann O. Scheimann, MD MPH1, Shaija Kutty, MD1, Buford Nichols, MD2, Wikrom Karnsakul, MD1
1- The Johns Hopkins University School of Medicine, Division of Pediatric Gastroenterology, Hepatology, and Nutrition
2- Baylor College of Medicine, Division of Pediatric Gastroenterology, Hepatology, and Nutrition
Congenital sucrase-isomaltase deficiency (CSID) is a genetic condition involving deficiency or absence of the enzymes sucrase and isomaltase (SI). The SI enzyme complex is located in the small intestine brush border and participates in hydrolysis of disaccharides to monosaccharides. In the absence of SI, undigested sugars exert an osmotic effect in the intestines causing abdominal pain, nausea, bloating, and/or diarrhea. The gold standard for diagnosing disaccharidase deficiency is via endoscopic duodenal biopsy assay. Challenges exist with the accuracy and interpretation of low disaccharidase levels, related to stringent handling requirements, sample degradation, and other intestinal disorders causing false-positive results. 13C-sucrose breath testing, which measures exhaled 13CO2 after intake of sucrose, is a non-invasive method for diagnosing sucrase deficiency. Another breath test, Trio-Smart®, can screen for small intestinal bacterial overgrowth (SIBO), a cause of false-positive CSID diagnosis during disaccharidase analysis. In a small case series, we sought to validate sucrase deficiency from abnormal disaccharidase assay using 13C-sucrose breath test, screen for SIBO by Trio-Smart® breath testing, and monitor clinical response to a trial of Sucraid® in children with suspected sucrase deficiency.
A case-series study was conducted on three teenagers with sucrase enzyme activity <25 uM/min/g protein from duodenal biopsies. Patient 1 was a 14-year-old girl with irritable bowel syndrome with diarrhea, type 1 diabetes mellitus, and polycystic ovarian syndrome who presented with symptoms of abdominal pain and diarrhea. Patient 2 was a 15-year-old girl with a history of Crohn’s disease, in histologic remission on adalimumab, who presented with abdominal pain and weight loss. Patient 3 was a 17-year-old boy with no significant medical history who presented with frequent loose stools. Patients completed both 13C-sucrose and Trio-Smart® breath testing at home after appropriate fasting and carbohydrate restriction, followed by a trial of Sucraid® replacement therapy. Improvement in symptoms was assessed at least four weeks after Sucraid® initiation.
Duodenal biopsies had low lactase, sucrose, and maltase levels without villous atrophy or increased intraepithelial lymphocytes. Patient 2 additionally had low palatinase. 13C-sucrose breath testing confirmed CSID in all patients with low sucrase activity of 1.88%, 1.96%, and 3.23% in patients 1, 2, and 3, respectively. Trio-Smart® breath testing was within normal limits, excluding SIBO. All patients were started on Lactaid®. After Sucraid® initiation, all patients reported symptomatic improvement without complete resolution.
Diagnosing CSID via disaccharidase assay presents challenges in accuracy and interpretation of results due to concern for false-positive results secondary to sample degradation or SIBO. In this small case series, a combination of 13C-sucrose and Trio-Smart® breath testing was used to confirm CSID diagnosis and screen for confounders. Initiation of Sucraid® enzyme replacement therapy improved, but did not fully resolve, reported symptoms. Additional larger-scale studies may be beneficial for the evaluation of the utility of 13C-sucrose and Trio-Smart® breath testing in patients with low sucrose disaccharidase levels.