Evaluation of congenital sucrase isomaltase deficiency in childhoodfunctional gastrointestinal system diseases

Disaccharidases are hydrolase enzymes located in the intestinal brush border. Sucrase is responsible for the breakdown of sucrose into glucose and fructose. Sucrose is found in fresh fruits such as peaches and bananas and in sweets such as cookies and chocolate. Deficiencies in any of the disaccharidase enzymes can cause intolerance to these foods, leading to dyspepsia, bloating, and abdominal pain. Functional Gastrointestinal System Disorders (FGID) are a group of diseases that cannot be explained by biochemical and structural abnormalities and frequently include chronic and recurrent symptoms related to motor, somatic, autonomic, and emotional development. Congenital (Primary) Sucrase Isomaltase Deficiency (CSIE) is an inherited enzyme deficiency caused by mutations in the sucrase isomaltase (SI) gene. It is inherited as an autosomal recessive; homozygous or heterozygous mutations have been identified. More than 40 pathogenic mutations have been identified, affecting various aspects of gene function, resulting in multiple phenotypes with a wide range of enzymatic activities and clinical spectrum. While the frequency of CSIE was previously 0.05-0.2% in Europe, it is now known to be 2-9%. The true prevalence of CSIE is not clearly known due to differences in terminology, various diagnostic methods with unclear performance characteristics, the presence of multiple genomic abnormalities with wide phenotypic variability, overlap of complaints with other gastrointestinal disorders, and lack of epidemiological data. Methods such as breath tests, genetic testing, and oral testing of various formulations of the enzyme have been used to diagnose disaccharidase deficiencies. The gold standard in diagnosis is to check the disaccharidase level in the endoscopic biopsy sample. However, this is an invasive procedure. The current diagnostic method is to perform sucrase isomaltase gene mutation exon analysis. The aim of our study is to evaluate the frequency of CSIE in patients presenting with FGID symptoms, to assess the clinical complaints in patients with positive mutations, and to evaluate the effect of treatment on the quality of life in patients for whom treatment is initiated. Patients aged 0 to 18 years who applied to Pamukkale University Faculty of Medicine Hospital Pediatric Gastroenterology outpatient clinic with FGID symptoms between May 2022 and January 2023 were included in our study. Our study is a single-center, cross-sectional, and prospective study conducted at Pamukkale University Pediatric Gastroenterology outpatient clinic. The presenting complaints of all patients included in the study were recorded, and FGID diagnoses were determined according to the Rome IV criteria. Diseases such as infectious diarrhea, celiac disease, inflammatory bowel disease, and food allergies were excluded by performing history, physical examination, blood, and stool tests. During the examinations to evaluate the underlying organic etiology, 2 ml of blood was allocated to the EDTA tube, and CSIE mutation analysis was performed in all patients. An application for medication (Sacrosidase) was made to the Ministry of Health for patients whose mutation was detected positive, who did not benefit from treatment for FGID, and who followed a sucrose-restricted diet and benefited from the diet. Sacrosidase enzyme replacement therapy was started in patients whose applications were approved. In order to evaluate the response to treatment, the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) (Appendix-1) was applied before the treatment and at the 2nd week after the treatment. Mutation analysis was performed on all 290 patients included in the study, revealing CSIE mutation in 17 (5.9%) patients. Among the cohort, 119 (41%) patients presented with abdominal pain, which emerged as the most common complaint. According to the Rome IV criteria, diagnoses comprised 110 (37.9%) patients with functional abdominal pain, 59 (20.3%) with Irritable Bowel Syndrome (IBS), 42 (14.5%) with functional dyspepsia, 35 (12.1%) with functional diarrhea, and 20 (6.9%) with functional vomiting. Mutations were detected in 7 (5.8%) of the 119 patients presenting with abdominal pain, 2 (5.7%) of the 35 patients with diarrhea, and 6 (10.1%) of the 59 patients with IBS symptoms. Additionally, 1 (4.7%) mutation was found among the 21 patients presenting with vomiting. Heterozygous mutations were detected in all positive cases, with no instances of homozygosity observed. Endoscopy was performed in 34 (11.7%) patients, with positive mutation detected in 3 of these cases. Sacrosidase enzyme treatment was initiated in 5 of the 17 positive patients. The PedsQL 4.0 Quality of Life Scale was administered before and 2 weeks after treatment, revealing an improvement in total scores across all patients. Disaccharidase deficiencies are more prevalent in children than previously believed. CSIE should be considered in patients presenting with FGID complaints. Guidelines advocating for enzyme testing inclusion in the pediatric endoscopy procedure for abdominal pain, indigestion, or diarrhea may alter practice and facilitate early diagnosis. Future utilization of genetic testing may unveil diverse mutations responsible for these deficiencies. Further research is imperative to establish a diagnostic protocol for identifying patients with functional impairments and determining subsequent treatment needs. Keywords: Congenital sucrase isomaltase deficiency, disaccharidase deficiency, functional gastrointestinal system diseases, PedsQL, stomach ache