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Enzyme replacement therapy for hypophosphatasia has shown promising results in human clinical trials, reducing mortality in hypophosphatasia and improving chondromalacia, lung function and exercise milestones in these patients [44]

Although we performed multivariate adjustments, residual confounding may persist due to unmeasured factors such as dietary habits (e.g., irregular intake of animal-derived foods or B12-fortified products), unrecorded use of nutritional supplements, and genetic predispositionsparticularly MTHFR polymorphisms, which are known to influence homocysteine metabolism and folate cycling, thereby potentially altering the functional demand for vitamin B12

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