Disaccharidase deficiencies, including sucrase-isomaltase deficiency, can cause chronic gastrointestinal symptoms in children. While duodenal biopsies remain the diagnostic gold standard, results may be confounded by specimen handling variability or secondary mucosal injury. The noninvasive 13C sucrose breath test (13CSBT) accurately detects sucrase deficiency, including congenital sucrase-isomaltase deficiency (CSID), while the Trio-Smart® breath test (BT) identifies small intestinal bacterial overgrowth (SIBO), a potential cause of secondary enzyme deficiency. We conducted a retrospective review of 25 pediatric patients with disaccharidase deficiencies on duodenal biopsy and normal villous architecture. Patients underwent 13CSBT and/or Trio-Smart® BT to evaluate for true CSID or SIBO. Clinical outcomes and treatment responses were assessed. Of 21 patients with low sucrase activities who completed 13CSBT, only 7 (33.3%) had abnormal results consistent with CSID. Six patients received sacrosidase, with three reporting symptom improvement. Of 15 patients who underwent Trio-Smart® breath testing, 9 (60.0%) had abnormal results suggestive of SIBO and responded to antimicrobial treatment. Two patients had abnormal results on both tests. Interestingly, low palatinase levels were associated with abnormal 13CSBT in some cases, though not consistently. Biopsy-based diagnosis may overestimate true CSID due to secondary causes or technical artifacts. Combined use of the 13CSBT and Trio-Smart® BT provides a noninvasive strategy to help distinguish primary or secondary sucrase deficiency, improving diagnostic accuracy and avoiding unnecessary lifelong enzyme therapy. We propose a diagnostic algorithm that integrates biopsy and BT results to guide evaluation and reduce misclassification of CSID.

Congenital sucrase-isomaltase deficiency (CSID) is an inherited metabolic disorder causing chronic gastrointestinal symptoms and malnutrition when untreated. Most CSID patients are likely to remain under- or misdiagnosed. This study aimed to investigate prevalence of CSID among patients with autism spectrum disorder (ASD) presenting with irritable bowel syndrome (IBS) symptoms via prospective SI gene sequencing. A prospective cross-sectional study was conducted on 98 ASD patients exhibiting gastrointestinal symptoms consistent with IBS. Participants were assessed according to Rome IV criteria and underwent SI gene sequencing. Demographic, clinical, and dietary data were collected and analyzed. Sucrose content in various fruits and vegetables was evaluated using three-day food record, and gastrointestinal symptoms were rated on Likert scale. Seven patients (7%) were diagnosed with CSID based on SI gene analysis, revealing six different variants, including four novel mutations. One patient was homozygous for one variant, and six patients were heterozygous. Clinical presentations predominantly included diarrhea, abdominal pain, and bloating, with two patients showing growth retardation. One patient was diagnosed in adulthood. Food allergy and lactose intolerance were the misdiagnoses prior to CSID diagnosis in two patients. Real prevalence of CSID is likely underestimated. Clinical heterogeneity and non-specific symptoms contribute to diagnostic challenges. Gastrointestinal symptoms consistent with IBS in ASD patients should include CSID in differential diagnosis. Early genetic screening for SI variants in ASD patients with IBS symptoms can facilitate timely diagnosis and management, improving outcomes. Heterozygous variants of the SI gene should also be considered, as heterozygous patients can exhibit typical CSID symptoms.

Congenital sucrase isomaltase deficiency (CSID) is a rare autosomal recessive monogenic disorder of small intestinal malabsorption and manifests typically in early childhood with chronic osmotic diarrhoea. Though there have been case reports in adults presenting with hypercalcemia and renal calculi in CSID, this is quite rare in children. We hereby report a 6-year-old boy who presented with recurrent episodes of calcium oxalate calculi without any gastrointestinal symptoms and was confirmed as having sucrase isomaltase deficiency by genetic analysis.

Congenital sucrase isomaltase deficiency (CSID), an inherited carbohydrate malabsorption disorder, is difficult to diagnose because of overlapping symptoms with other gastrointestinal (GI) diseases. An at-home study was conducted in CSID and healthy adults to evaluate the diagnostic utility of self-reported GI symptoms following administration of a sucrose challenge. This study investigated the optimum symptom scoring with a sucrose challenge symptoms test (SCST) for diagnosing CSID in 45 confirmed patients and 118 healthy controls. Subjects self-reported the severity of GI symptoms using a 10-point Likert scale after ingesting 50 grams of sucrose on an empty stomach. The receiver operator characteristics curve (ROC) was used to identify the diagnostic variable with the highest Youden Index, a measure of diagnostic performance. All six symptoms were significantly worse in the CSID group within 2 hours after the sucrose challenge. The diagnostic variable with the highest Youden Index was worsening in global symptoms scores at 1- and 2-hours (11.7 [CSID] vs 3.2 [Controls]; P<0.001.) Optimized by gender, the sensitivity and specificity for this diagnostic variable were 87% and 81%, respectively. The SCST is a simple, non-invasive at-home test that can aid in a CSID diagnosis.

Congenital sucrase-isomaltase deficiency is an autosomal recessive inherited disaccharidase deficiency characterized by chronic osmotic diarrhea. In this study, the genotype-phenotype relationships of close relatives of an index case with congenital sucrase-isomaltase deficiency were investigated. A 23-month-old female patient with a sucrase-isomaltase gene c.317G>A (p.C106Y) homozygous mutation was diagnosed as an index case and her pedigree analysis was performed subsequently. The family members with and without sucrase- isomaltase gene mutations were compared in terms of clinical symptoms. The study included 109 cases [mean age ± SD: 22.6 ± 17.2 years (0.1-75 years), 61 males (56%)] of 130 family members of the index case. Sucrase-isomaltase gene c.317G>A (p.C106Y) heterozygous mutation was detected in 27 cases (24.7%); 14 (51.9%) were male and had a mean age of 23.2 ± 18.3 years. The most common complaints of 12 (44.4%) symptomatic patients with mutations were abdominal pain (37%), gas irritability (33.3%), bloating (22.2%), and foul-smelling stools (18.5%). Compared with the cases without mutation, a statistically significant difference was observed in the incidence of gas irritability, foul-smelling stool, ≥2 gastrointestinal symptoms, postprandial complaints, and food allergy (P = .005, P = .047, P = .049, P = .017, P = .021, respectively). Sacrosidase enzyme replacement was applied to 7 patients whose symptoms did not improve with dietary elimination. Clinical response was obtained after enzyme treatment. Despite its autosomal recessive inheritance, congenital sucrase-isomaltase deficiency can also be symptomatic in heterozygous individuals. Further studies are required to clarify the genotype-phenotype relationship and management of the disease.