Gastroenterology (GI) Basics Kathleen J. Motil, M.D., Ph.D. USDA Children’s Nutrition Research Center Baylor College of Medicine Houston, TX 77030

Disclosures I am a Section Editor for Up-To-Date, Inc., an electronic textbook of medicine. I do not have relevant financial relationships with the manufacturers of commercial products and/or providers of commercial services discussed in this presentation. I will not discuss unapproved or investigative use of a commercial product or device in my presentation.

Parental Concerns “My daughter eats all of the time, but she doesn’t gain weight.” “My daughter screams constantly. I know something is wrong.” “My daughter’s stomach is full of air. It must hurt.” “My daughter won’t go to the bathroom unless I give her something. I don’t want her to become addicted.”

Objectives Recognize problems related to GI dysmotility in Rett syndrome Recognize “trigger” signs to call your physician Understand the reason for selected GI tests Understand approaches to treat GI dysmotility in Rett syndrome

GI Problems in Rett Syndrome Feeding difficulty 81% Chewing dysfunction 56% Swallowing dysfunction 43% Gastrointestinal dysmotility 92% Gastroesophageal reflux 38% Delayed gastric emptying 14% Biliary tract disease 3% Gas bloating ? Constipation 80% Motil KJ, J Pediatr Gastroenterol Nutr, 2012

Enteric Nervous System MeCP2 found throughout GI tract MeCP2 found specifically in enteric nervous tissue MeCP2 found throughout development of GI tract GI dysmotility in Rett syndrome mediated directly through ENS dysfunction because of abnormal MECP2 (protein) Wahba G, Neurogastroenterol Motil, 2015

Chew/Swallow Dysfunction Definition: poor jaw movement, tongue mobility/propulsion, delayed initiation of swallow, pooling of food in sinuses, laryngeal liquid penetration/aspiration Trigger: Meals > 30 min, choking with meals, poor weight gain Test: OT/Speech assessment, Swallow function study, BMI Treatment: OT/Speech therapy, alternative feeding methods

Gastroesophageal Reflux Definition: involuntary reverse passage of acid, food from stomach to esophagus/mouth due to poor motility of esophagus, LES, stomach Trigger: irritability, vomiting, night awakening, feeding refusal, wheezing Test: Medical history, UGI series, upper endoscopy/biopsy, gastric emptying scan Treatment: dietary, position, medications (PPI, prokinetic), surgery (fundoplication)

Biliary Tract Disease Definition: three disorders Cholecystitis (inflammation) Cholelithiasis (gallstones) Biliary dyskinesia (dysmotility) Trigger: abdominal pain, jaundice, vomiting Test: AUS, HIDA scan Treatment: surgery (cholecystectomy)

Gas Bloating Definition: gas trapping due to air swallowing (bruxism, breath holding, hyperventilation) or bacterial fermentation of undigested CHO Trigger: abdominal distention, discomfort Test: blood (celiac disease), stool (giardiasis, H pylori), H2 breath test (lactose intolerance, SBBO), AXR (constipation) Treatment: diet (↓ CHO/sorbitol, gluten-free, lactase enzyme), medications (simethicone, antibiotics, laxatives, probiotics)

Constipation Definition: defecation difficulty, bowel movements < 2x/week, Trigger: large or pebble hard stool, blood on stool, abdominal pain,  gas, poor appetite, vomiting, UTI, diarrhea Test: Medical history, abdominal/rectal exam; AXR, barium enema, rectal manometry/biopsy, colonoscopy/biopsy Treatment: diet ( fiber, sorbitol), medications (softener/pusher laxatives, probiotics, suppositories, enemas) surgery (cecostomy, appendicostomy), physical activity

Gastrointestinal Crises Severely ill, abdominal pain, abdominal distention, vomiting Surgical emergencies (stomach, intestines) Volvulus (twisting) Intussusception (sliding) Perforation (hole) Cause of abdominal crises unknown Air swallowing alone does not result in intestinal perforation Chronic constipation, megacolon may increase risk for obstruction Not unique to Rett Syndrome

Future Research Enteric nervous system Intestinal microbiome Role of MECP2 in synaptic transmission, neurotransmitter synthesis and activity Differences in genotype-phenotype outcomes Intestinal microbiome Patterns of microbial colonization, metabolic end-products

Summary GI problems (chewing/swallowing difficulties, feeding refusal, gastroesophageal reflux, delayed gastric emptying, gas bloating, constipation) commonly found in RTT GI problems caused by dysmotility of GI tract, presumably due to abnormalities in enteric nervous system Any symptom that causes parental concern should be evaluated by a physician Treatment strategies should be discussed with a physician to improve symptoms, avoid complications, improve quality of life