Response to V. Martín-Dominguez Et Al.: Re-Evaluating the Diagnostic Approach to Lactose Malabsorption

The article by Martín-Domínguez V et al. proposes genetic testing as the first diagnostic test for lactose malabsorption, given its high concordance with the lactose breath test (LBT). We think that conceptual and methodological inconsistencies undermine this conclusion.

The genetic test, LBT, and Gaxilose test measure different physiological aspects such as genetic predisposition, lactose malabsorption, and lactase enzymatic activity, respectively, so the three tests cannot be used interchangeably. Diagnostic bias is introduced by the study's limited use of biopsy confirmation, disregard for secondary hypolactasia, and reliance on genotype as a reference standard.

Additionally, the clinical validity of the results is compromised by the high variability in genetic polymorphisms across populations, unreported comorbidities like SIBO or IBS, and dubious symptom assessment during testing. Evidence from multicenter studies demonstrates that the Gaxilose test offers high sensitivity and specificity and is well tolerated.

We conclude that genetic testing alone cannot replace functional or structural assessments and warn that the study's conclusions may lead to misleading diagnostic recommendations in real-world clinical practice.