The Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of the activity of alkaline phosphatase in serum and bone.
Symptoms are highly variable in their clinical expression, ranging from stillbirth without mineralized to premature loss of teeth without bone symptoms bone. Depending on the age at diagnosis, six clinical forms are currently recognized: perinatal lethal, perinatal benign, child, children, adults and odontohypophosphatasia. In perinatal lethal form, patients exhibit a markedly deteriorated mineralization in utero. In the benign form these symptoms improve spontaneously. Clinical symptoms of infantile form are respiratory complications, craniosynostosis, widespread demineralization and stunted changes in metaphysis. The infantile form is characterized by skeletal deformities, short stature, and waddling gait, and the adult form of stress fractures, thigh pain, chondrocalcinosis and marked osteoarthropathy. The odontohypophosphatasia is characterized by the premature fall of fully rooted primary teeth and / or severe tooth decay, often they are not associated with abnormalities of skeletal system.
The disease is due to mutations in the gene for alkaline phosphatase level different organs such as liver, bone and kidney, encoding unspecific tissue alkaline phosphatase (ALPL). The diagnosis is based on molecular analysis of the this gene. Serum alkaline phosphatase activity (AP) is significantly reduced in hypophosphatasia, while urinary phosphoethanolamine (PEA) is increased.
Genetic counseling of the disease is complicated by the variable inheritance pattern (autosomal dominant or autosomal recessive), the existence of the uncommon prenatal benign form, and incomplete penetrance of the trait. There is no curative treatment for hypophosphatasia, but symptomatic treatments have proven to be beneficial.
Gene or region studied