Hypophosphatasia: the importance of knowing in advance

Abstract

Hypophosphatasia (HPP) is a rare and highly variable genetic disorder of metabolism characterized by markedly reduced serum alkaline phosphatase (ALP) activity as a result of defective production of tissue-non-specific alkaline phosphatase (TNSALP). HPP is known to affect fetuses in utero and also neonates, children, and adults. Severity ranges significantly, from lethal to mild and clinical presentations include rickets or osteomalacia, osteoporosis, respiratory failure and seizures. Odontohypophosphatasia has only dental manifestations. Low total ALP in serum is the hallmark of HPP, whereas elevated serum concentrations of pyridoxal-5-phosphate and phosphoethanolamine levels represent sensitive and specific biomarkers for HPP. Several pathognomonic radiographic changes are suggestive of HPP. Recently, asfotase alfa, a bone targeted recombinant TNSALP has been used to treat HPP with significant success, highlighting the importance of early diagnosis and intervention. This review describes our current knowledge of HPP, reporting on the epidemiology, classification, clinical presentation and main diagnostic features of the disease, as well as more recent therapeutic approaches.