P489 - APPLICATION OF MOLECULAR GENETIC TESTING IN CLINICAL PRACTICE FOR DISACCHARIDASE DEFICIENCIES

P489

APPLICATION OF MOLECULAR GENETIC TESTING IN CLINICAL PRACTICE FOR DISACCHARIDASE DEFICIENCIES

N. Grosup Friedova^1,2,*, M. Kollerova³, J. Tajtlova², M. Langova², P. Kohout¹

¹Department of Internal Medicine 3rd Faculty of Medicine Charles University, ²Department of Medical Genetics, ³Nutrition and Dietetics Center, Thomayer University Hospital, Prague, Czech Republic

Rationale: Disaccharidase deficiency (e.g., lactase, sucrase, trehalase) impairs disaccharides digestion, causing bloating, cramps and diarrhea. Diagnosis relies on clinical evaluation, H₂ breath test, or small intestinal mucosal immunohistochemistry. Treatment involves enzyme replacement and/or dietary elimination. Secondary forms are often reversible after managing the underlying condition. Primary (congenital) forms are rare, confirmed by genetic testing, and require lifelong dietary management. Molecular testing for lactase deficiency is common, while testing for sucrase and trehalase is not routine. In cases with non-confirmatory lactase genotypes but persistent symptoms, or when histology suggests a primary defect, genetic testing for sucrase and trehalase deficiencies has been implemented.

Methods: Molecular genetic testing for lactose intolerance, using RT-PCR, detects the LCT 13910C>T and 22018G>A polymorphisms. Primary trehalase deficiency is caused by pathogenic variants in the TREH gene, congenital sucrase-isomaltase deficiency results from mutations in the SI gene. Exome sequencing (SSELXT HS Human All Exon V8+NCV panel on the NextSeq DX 500/550 sequencer) is used to distinguish primary from secondary forms.

Results: From 2017 to 2025, 247 patients with suspected primary lactase deficiency were genetically analyzed, confirming primary deficiency in 80 cases. Testing was extended in 2023 to include TREH, with 4 patients examined and one case of primary deficiency identified. In 2024, sucrase deficiency testing was initiated, confirming primary sucrase-isomaltase deficiency in one patient, 20 years after symptom onset.

Conclusion: Molecular genetic testing for trehalase and sucrase deficiencies is now routine in our department, providing essential insights into diagnosing and managing disaccharidase deficiencies. Exome sequencing may also identify previously unknown genes associated with these disorders.

Disclosure of Interest: None declared