Hypophosphatasia is a rare inborn metabolic disorder, characterized by a genetic defect in the gene (ALPL) coding the tissue-nonspecific alkaline phosphatase (TNSALP). Defective bone mineralization and dental anomalies are the main features of the disease. The clinical expression is highly variable, ranging from lethal type to less severe bone and joint disorders. According to age, different forms have been described: perinatal (respiratory complications, in most case very severe and lethal), infantile (rickets, vitamin-B6 dependant seizures), juvenile (dental lesions, short stature, bone deformations, waddling gait), adult hypophosphatasia (history of rickets, pseudo-fractures, delayed consolidation of fractures, pyrophosphate arthropathy) as well as odonto-hypophosphatasia. Different radiographic anomalies may be observed at different stages of the diseases; rachitic changes, bone deformations, functional cranisosynostosis in children; in adults radiographs may show stress fractures, sometimes complete fractures with poor healing, chondrocalcinosis with calcium pyrophosphate crystal deposition. The diagnosis is based on laboratory findings: marked reduction of serum alkaline phosphatase activity, increased urinary excretion of phosphoethanolamine and inorganic pyrophosphates, increased serum pyridoxal-5’-phosphate. Histologically, mineralization of osteoid bone tissue is defective. Genomic DNA sequencing can detect mutations of ALPL gene in 95% of cases; more than 200 mutations have been described (http://www.sesep.uvsq.fr/03_hypo_mutations.php). The mode of inheritance is variable and it complicates the genetic counselling; hypophosphatasia may be inherited in an autosomal dominant or autosomal recessive manner. There is no established treatment of hypophosphatasia. Vitamin D supplementation may induce hypercalcemia and hypercalciuria. Vitamin B6 supplementation is given in children suffering from epilepsy and NSAID may be useful to treat bone inflammatory lesions. Encouraging results have been observed in patients given daily subcutaneous parathyroid hormone or teriparatide. Very promising results have recently been obtained by enzyme replacement therapy for severe infantile forms of the disease.