Biochemical and clinical changes during enzymatic replacement therapy in hypophosphatasia: three real-world cases in...

Hypophosphatasia (HPP) is a rare recessive or dominant autosomal disease caused by loss-of-function variants in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Molecules involved in the pathogenesis of HPP are alkaline phosphatase (ALP), inorganic pyrophosphate (PPi; an inhibitor of bone mineralization), pyridoxal-5'-phosphate (PLP; responsible for the neurological complications) and phosphoethanolamine. Asfotase alfa is a recombinant, bone-targeted, human TNSALP approved to treat patients with HPP. Its clinical effectiveness has been demonstrated in real-world settings across international HPP registries. However, evidence from routine clinical practice in Spain is lacking. Here, we report three Spanish cases of HPP treated successfully with asfotase alfa: a girl diagnosed at 3 months; a woman diagnosed at age 47 years; and a 27-year-old woman with paediatric-onset symptoms. In all cases, asfotase alfa treatment was associated with an increase in serum ALP, marked reductions in plasma PPi and PLP, and marked improvements in symptoms and physical performance. Our series of HPP cases confirms the beneficial effects of asfotase alfa on biochemical and clinical outcomes, consistent with evidence from randomized clinical trials.