Integrating Novel Diagnostic Strategies into Practice: Key Points. Stanley Cohen, MD Emory University Atlanta, Georgia
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1 Integrating Novel Diagnostic Strategies into Practice: Key Points Stanley Cohen, MD Emory University Atlanta, Georgia
2 Disclosure Research: Janssen, Covidien/Medtronics, AbbVie, AstraZeneca and QOL Speaker: Janssen, Prometheus, AbbVie, Nestles Institute, Nutricia and Lupin Consultant: Janssen, Covidien/Medtronics, AbbVie, AstraZeneca and QOL Shareholder: Nutrition 4 Kids Advisor: Nutrition 4 Kids Luminal fluid
3 Patient Case HISTORY & PE MEDICATION LABS PROGRESS NOTES OTHER 17 year-old female HPI Originally had issues with GERD, responded to a PPI Periumbilical pain intermittently, often waking her and often with diarrhea, can last for days Increased with stress at school Somewhat better with an anticholinergic prn PMH On BCP, gabapentin, and iron Labs CBC, ESR, CMP, RAST, ttg, thyroid, lipids all wnl Stool studies requested, but not performed GD / colon 2 yrs prior --nl
4 Searching for IBS: Differential Diagnoses Bile acid diarrhea Microscopic colitis Celiac disease Non-celiac gluten sensitivity Food allergy Carbohydrate maldigestion
5 Patient Follow-Up PROGRESS NOTES HISTORY MEDICATION LABS OTHER EGD/colonoscopy visually and histologically normal Disaccharidases Lactase 0.0 (abnormal < 15) Sucrase 19.4 (abnormal <25) Maltase 71.0 (abnormal < 100) Palatinase 4.0 (abnormal < 5) Patient diagnosed with pan-disaccharidase deficiency with hypolactasia
6 Understanding Carbohydrate Malabsorption Polysaccharides Disaccharides Monosaccharides Amylase starch glycogen lactose isomaltose maltose sucrose fructose glucose galactose Palatinase (isomaltase) Lactase Maltase Sucrase 1. Treem WR. J Pediatr Gastroenterol Nutr. 2012;55(Suppl 2):S7-S Canani RB et al. Nutrients. 2016;8:157.
7 Clinical Consequences of Carbohydrate Malabsorption Pain Diarrhea Gas Luminal fluid Bloating 1. Treem WR. J Pediatr Gastroenterol Nutr. 2012;55(Suppl 2):S7-S Canani RB et al. Nutrients. 2016;8:157.
8 Key Intestinal Disaccharidases Maltase Palatinase Used to approximate glucoamylase Not explicit to maltase, more related to SI (75%) than MGAM (only 25%) Used to approximate isomaltase SI responsible for most isomaltase activity (>70%) Digests starch Lactase Sucrase Specific to lactose, but lactase deficiency can be as high as 50% after 5 years of age 85% specific to sucrose Digests milk sugar Digests table sugar MGAM, maltase-glucoamylase; SI, sucrase-isomaltase. Quezada-Calvillo R et al. J Nutr. 2008;138:
9 Potential Etiologies of Key Disaccharidase Deficiencies Congenital lactase deficiency Genetic 1,2 Genetic Sucrase-Isomaltase Deficiency (GSID) Autosomal recessive (CSID) Symptomatic heterozygous carriers Compound heterozygotes Secondary causes 2 Celiac disease Bacterial overgrowth IBD Allergic enteropathy Acute gastroenteritis Giardiasis Other (eg, mucositis) CSID, congenital sucrase isomaltase deficiency; IBD, inflammatory bowel disease. 1. Cohen S. Molecular Cellular Pediatr. 2016;3:5. 2. Naim HY et al. J Pediatr Gastroenterol Nutr. 2012; 55(Suppl 2):S13-S20.
10 The Spectrum of GSID Phenotypes Phenotypes IV, VI Enzymatic activity Active sucrase, active isomaltase V Active isomaltase, absent sucrase VII Decreased sucrase, absent isomaltase I, II, III Completely inactive Naim HY et al. J Pediatr Gastroenterol Nutr. 2012; 55(Suppl 2):S13-S20.
11 Patients, % Presenting Symptoms of GSID Presenting Symptoms in GSID (N=65) Diarrhea Bloating/ gas Abdominal pain Irritability Diaper rash Failure to thrive Nausea/ vomiting IBS Treem WR. J Pediatr Gastroenterol Nutr. 2012;55(Suppl 2):S7-S13.
12 Symptoms of GSID: Infants vs. Adults more severe Symptom severity less severe Shorter length of GI tract Increased consumption of highcarbohydrate diet (juices, baby food fruits/vegetables, cereals) More rapid intestinal and colonic transit time available for alternative carbohydrate digestion pathways Changes in bowel flora may alleviate symptoms Diet control Carrier status, milder variants Ileal hyperproliferation May be misdiagnosed as IBS, lactose intolerance 1. Treem WR. J Pediatr Gastroenterol Nutr. 1995;21: Treem WR. J Pediatr Gastroenterol Nutr. 2012;55(Suppl 2):S7-S13.
13 Methods to Diagnose GSID z Small bowel biopsy 1,2 Genetic test 2 Sacrosidase response dose 2,3 Breath tests 2 Stool tests 1,2 Definitive diagnosis Often sent to specialty lab Buccal or saliva Detects 37 polymorphisms in SI gene Determined by decrease in GI symptoms Sucrose hydrogen or 13 C-sucrose ph, osmolality, reducing sugars Not specific for sucrose malabsorption SI, sucrase isomaltase 1. Treem WR. J Pediatr Gastroenterol Nutr. 2012;55(Suppl 2):S7-S Cohen S. Molecular Cellular Pediatr. 2016;3:5. 3. Puntis JW and Zamvar V. Arch Dis Child. 2015;100(9):
14 Hydrogen-Methane Breath Test for GSID Sucrose load H 2 &/or methane Indirect test for CHO malabsorption (not specific for GSID) 1-3 Reduced CHO diet 24 hours before test and 12 hours of fasting 4 Colonic fermentation Catch breath into 6 tubes over 3 hours after ingesting sucrose solution 4 May produce symptoms in GSID patients due to consumption of sucrose 1,2 CHO, carbohydrate; GSID, genetic sucrase-isomaltase deficiency. 1. Ghoshal UC. J Neurogastroenterol Motil. 2011;17(3): de Lacy Costello BPJ et al. J Breath Res. 2013;7: Simren M and Stotzer P. Gut. 2006;55: Sucrose tolerance/malabsorption breath test. Commonwealth Laboratories Inc. Salem, MA.
15 How Common Is Disaccharidase Deficiency? Analysis of Mucosal Biopsies (N=27,875) 4% Other 55% No disaccharidase deficiency 45% 1 disaccharidase deficiency 21% 75% Sucrase deficiency (9.4% of biopsies) Lactase deficiency (34.7% of biopsies) Nichols BL et al. J Pediatr Gastroenterol Nutr. 2012;(Suppl 2):S28-S30.
16 Primary Results 5,362 EGDs 963 (18%) Disaccharidase testing 430 (45%) Lactase deficiency only 73 (7.6%) Sucrase deficiency 44 (60%) 25 (34%) 4 (5%) Pan-disaccharidase with lactase deficiency isolated
17 Pertinent Indications n=3,344 n=529 n=266 n=235 n=4 Abdominal pain 0.1 Diarrhea Nausea Weight loss Bloating
18 Most Patients With SD Had Multiple Symptoms Most Common Presenting Symptom Symptoms n (%) Abdominal pain 49 (78%) Diarrhea 27 (43%) Constipation 21 (33%) Nausea 19 (30%) Vomiting 15 (24%) Weight loss/failure to thrive 15 (24%) Note: Excludes patients with blood in stool (n=8) and missing (n=2).
19 Normal vs Abnormal Biopsies Normal Abnormal P-Value * N Age 13.0 ± ± 4.0 < 0.05 BMI < 0.05 Diarrhea week < 0.05 Isolated sucrase deficiency 3 1 Sucrase/lactase deficiencies Pan-deficiency (sucrase, lactase, maltase, palatinase) * P values similar when all patients included.
20 Sucrase Deficiency By Type Most Common Presenting Symptom Pan-Disaccharidase Deficiency Lactase/ Sucrase Deficiency Isolated Sucrase Deficiency P-Value N M/F 31/13 9/6 2/2 Age BMI, % Sucrase activity Abdominal pain Diarrhea Nausea Constipation FTT / Weight loss Normal histology , unable to calculate significance value. FTT, failure to thrive.
21 Patients, % Disaccharidase Test Results Disaccharidase Deficiency Among Patients with Abdominal Pain Lactase deficient Sucrase deficient Treating MD N % Tested
22 Sucrase Deficiency P=0.09 P=0.001
23 Integrating Novel Diagnostic Strategies into Practice Key Points Symptoms of disaccharidase deficiency can mimic IBS Sucrase deficiency is a genetic condition The different symptom patterns may be related to the different genotypes Testing for diasaccharidase deficiencies is best accomplished by breath testing or duodenal biopsies
Primary sucrase-isomaltase deficiency (SID) is an inherited
Variable Use of Disaccharidase Assays When Evaluating Abdominal Pain Stanley A. Cohen, MD, and Hannah Oloyede, MS Dr Cohen is director of IBD research at the Children s Center for Digestive Health Care,
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