Sacrosidase 8,500units/ml oral solution

Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population.

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BACKGROUND/AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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PURPOSE: The sucrase-isomaltase (SI) gene encodes sucrase-isomaltase enzyme found on the intestinal brush-border that has a major function in the hydrolysis of sucrose, oligosaccharides, and starch. Mutations disrupting its function cause genetic sucrase-isomaltase deficiency (GSID). Variants leading to mild to moderate reductions in enzyme activity may mimic disorders of gut-brain interaction (DGBI), and differentiating the etiology is crucial for initiating appropriate treatment. In this study, we aim to determine the rate of GSID in individuals who underwent whole exome or clinical exome sequencing (WES/CES) for indications other than chronic gastrointestinal symptoms in a single-center cohort. We also focused on a second group, the pediatric DGBI patients, who underwent SI gene analysis, to evaluate the rate of GSID in pediatric DGBI patients and assess the clinical utility of SI gene testing in GSID diagnosis. METHODS: We retrospectively reviewed 980 patients who underwent WES/CES between 2017-2022, and 148 pediatric patients with DGBI evaluated between May 2021 and August 2022 who received SI gene analysis. RESULTS: The frequency of symptomatic GSID was found to be 0.3% among patients who underwent WES/CES, whereas it was 10% among pediatric DGBI patients. In DGBI patients carrying SI gene mutations, clinical improvement with a sucrose- and starch-free diet in combination with a sacrosidase response proved effective for establishing a diagnosis in all cases. CONCLUSION: GSID has been frequently detected among pediatric DGBI patients. SI gene analysis combined with a sucrose-restricted diet and a sacrosidase challenge provides a reliable, non-invasive approach for definitive diagnosis.

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Background and pathophysiology of congenital sucrase-isomaltase deficiency (CSID) An uncommon hereditary condition known as CSID affects around 0.05%–0.2% non-Hispanic Whites; meanwhile, African-Americans and White Hispanics exhibit a lower prevalence. As many as 5 in 100 people may be affected by this disorder in the native communities of Canada, Alaska, and Greenland1. CSID is characterized by a lack of the sucrase-isomaltase (SI) enzyme complex, usually present in the brush border of the small intestine, which is necessary for the dissociation of α-glycosidic bonds in sucrose and maltose. At the molecular level, homozygous or heterozygous mutations on chromosome 3q25-q26 lead to improper synthesis and transportation of the SI gene. Ouwendijk et al2 were the first to describe a mutation in the SI gene linked to CSID. Such mutations have also been demonstrated to increase the incidence of irritable bowel syndrome (IBS), which shares symptoms and clinical characteristics with CSID3. Over 40 known mutations in the SI gene cause CSID4. Sucrase activity is typically decreased in CSID patients, but the activity of isomaltase varies from nonexistent to fairly normal, due to which nutrients from ingested starch and sucrose cannot be adequately absorbed when this enzyme complex is insufficient5. Clinical presentation and diagnosis of CSID A lack of SI can result in carbohydrate malabsorption, characterized by cramping, bloating, gas, and watery, osmotic-fermentative diarrhea6. Patients may suffer from persistent malnutrition and failure to thrive in more complicated situations7. After an infant is weaned and is introduced to a starch-rich and sucrose-rich diet, such as sugar, grains, and fruits, CSID gradually becomes apparent. However, others may have milder gastrointestinal symptoms either from start or for a long time before they are identified in early adulthood8. Health care professionals have several options to help them diagnose CSID. Any infant who develops severe, watery diarrhea after consuming milk and glucose should be evaluated for CSID. Clinical evaluation, distinctive symptoms, a full patient history, or specialist testing may all help confirm a diagnosis of this illness. However, a small intestinal biopsy checked for disaccharidase activity is the standard test for CSID diagnosis; other less invasive investigations are the 13C-sucrose or sucrose hydrogen methane breath test. Another approach can be gene sequencing1. Current treatment guidelines for CSID Dietary management with a low-sucrose or sucrose-free diet is the primary treatment for CSID. Starch-free or a low-starch diet may also be recommended, particularly during the initial years of life. While some affected persons may develop sucrose tolerance in their 20s, others may remain sucrose intolerant throughout their lives. In 1998, the Food and Drug Administration (FDA) authorized using multidose sacrosidase oral solution (Sucraid) to treat CSID. This oral solution contains sacrosidase derived from baker’s yeast and glycerin and is used as an enzyme replacement therapy9. Sacrosidase is a β-fructofuranoside fructohydrolase that hydrolyzes sucrose. It does not interact with oligosaccharides having 1,6 glucosyl linkages, in contrast to human intestine SI. In vitro, it is exceedingly potent, with 9000 IU of activity per milliliter and about 6000 IU of sucrase activity per milligram of protein. When combined with water, it has no flavor and is stable when refrigerated. This formulation has also shown tolerance to pH variations down to a pH of 1.5, and taking the enzyme with extra protein prevents the enzyme from being degraded by intragastric pepsin10. Many of the symptoms brought on by sucrose consumption can be alleviated with the use of Sucraid for those with this illness. Sucraid approval was based on the 3 clinical trials that evaluated the efficacy of sacrosidase in patients with CSID. In the first trial by Treem et al11, the sucrose hydrogen breath test results showed a dramatic increase in sugar digestion efficiency. Sacrosidase was found to be most effective at higher doses. Similar findings were reported by Treem et al10 in another study. Moreover, sacrosidase significantly reduced both the frequency and intensity of gastrointestinal discomfort, as demonstrated by the long-term study conducted by QOL Medical, LLC12. On September 7, 2022, the FDA approved Sucraid single-use containers to treat CSID in patients who weigh more than 15 kg or 33 pounds. Sacrosidase is now marketed in both multidose and single-use vials. These new single-use containers would be much more practical and facilitate patient medication management13. Limitations of sacrosidase (Sucraid) The introduction of single-use containers means greater convenience for patients and reduced cost. Sacrosidase, as of now, is the only treatment for CSID, but it comes with limitations, such as its inability to break down certain sugars produced during starch digestion, so the diet’s starch intake may need to be limited. People with diabetes mellitus need to consult their doctors before taking Sucraid to avoid unannounced fluctuations in blood glucose levels. Patients can also experience some adverse effects, such as allergic reactions, which may cause swelling or difficulty breathing. Furthermore, QOL Medical is the only authorized manufacturer of the approved drug. News by FDA in 2018 reported a shortage in the production of Sucraid, which led to the distribution of an unapproved batch for patients with severe CSID14. In 2021, a cross-sectional study led by Smith and colleagues demonstrated a significant improvement in patients’ symptoms and quality of life after treatment with sacrosidase. However, more than 85% of participants indicated that CSID had various effects on their daily lives even after receiving treatment. The majority complained that living with CSID harmed their social lives. Irritability, awkwardness, and feeling left out were the top 3 reported emotional effects8. Conclusion The drug’s limitations, impact on patient’s quality of life, and psychological well-being demands an alternative, better, and more efficient treatment option for CSID. Until then, the production of Sucraid should be doubled since the latest FDA approval means increased demand. A phase 4 trial is underway consisting of 1100 pediatric patients to evaluate the therapeutic dose of Sucraid15. Hopefully, this trial’s results will help transform an efficient version of the drug. Lastly, for primary prevention, there should be awareness programs and genetic counseling to guide people about CSID, which would help in early diagnosis, ultimately making treatment more accessible. Ethical approval Not applicable. Source of funding None. Author contributions S.T.A. and M.A.S. have done the conceptualization. M.S.M., A.M., and M.M.N.U. conducted the literature and drafting of the manuscript. M.A.S. performed the editing and supervision. All authors have read and agreed to the final version of the manuscript. Conflict of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) Not applicable. Guarantor All authors take responsibility for the work, access to data and decision to publish.

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Background: Congenital sucrase–isomaltase deficiency (CSID) may mimic functional gastrointestinal disorders (FGIDs) and is likely underrecognized in pediatric practice. This study aimed to determine the frequency of sucrase–isomaltase (SI) gene variants among children with FGIDs and to evaluate genotype–phenotype associations and treatment-related quality-of-life outcomes. Methods: In this prospective cross-sectional study, children aged 0–18 years diagnosed with FGIDs according to Rome IV criteria were enrolled between May 2022 and January 2023. All patients underwent next-generation sequencing for SI gene variants. Clinical characteristics, FGID subtypes, and anthropometric data were recorded. Variant-positive patients received dietary sucrose restriction, and selected patients were treated with sacrosidase enzyme replacement. Symptom severity was assessed using the Numeric Rating Scale, and quality of life was evaluated with the Pediatric Quality of Life Inventory (PedsQL 4.0). Results: Among 290 children with FGIDs, SI gene variants were identified in 17 patients (5.9%). Variants were more frequently detected in children with irritable bowel syndrome–like symptoms. Clinical presentation was heterogeneous, and no consistent genotype–phenotype correlation was observed. Dietary intervention was associated with symptom improvement in compliant patients, while sacrosidase therapy led to significant improvements in both child- and parent-reported PedsQL scores. Conclusions: Sucrase–isomaltase deficiency is not uncommon among children with FGIDs and should be considered, particularly in those with IBS-like symptoms or diet-related complaints. Integrating genetic evaluation with targeted dietary and enzyme-based therapy may improve symptom control and quality of life in selected pediatric patients.

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Purpose: 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 13 C sucrose breath test ( 13 CSBT) 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.Methods: We conducted a retrospective review of 25 pediatric patients with disaccharidase deficiencies on duodenal biopsy and normal villous architecture.Patients underwent 13 CSBT and/or Trio-Smart BT to evaluate for true CSID or SIBO.Clinical outcomes and treatment responses were assessed.Results: Of 21 patients with low sucrase activities who completed 13 CSBT, 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 13 CSBT in some cases, though not consistently.Conclusion: Biopsy-based diagnosis may overestimate true CSID due to secondary causes or technical artifacts.Combined use of the 13 CSBT 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.

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