Hypophosphatasia is an autosomal recessive disorder caused by pathogenic variants in the ALPLM gene, which has the highest prevalence in individuals with Asian or Mennonite ancestry. The disease presentation represents a clinical spectrum that may be divided into six recognized forms that vary in their age of onset and severity. Perinatal (lethal) hypophosphatasia presents prenatally with fatal respiratory insufficiency and hypercalcemia; this form of the disease usually results in stillbirth or death shortly after birth. Perinatal (benign) hypophosphatasia initially presents with a skeletal structure similar to the perinatal form, but will develop into either the childhood or adult form; life expectancy is not decreased. Infantile hypophosphatasia presents between birth and six months of age, at which point patients will develop rickets and hypercalcemia; life expectancy is not decreased. Childhood hypophosphatasia can present at any point during childhood with unexplained fractures, rickets, bone and joint pain, and early tooth loss; life expectancy is not decreased. Adult hypophosphatasia usually unrecognized until adulthood. Patients have dental issues, leg/foot fractures and pain, and life expectancy is not decreased. Odontohypophosphatasia causes early loss of baby teeth and an increased risk of developing cavities; life expectancy is not decreased. It is not currently possible to predict the type and severity of disease that will develop based on the pathogenic variants inherited.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.