RE VENTURES I

Hypophosphatasia (HPP) is a rare genetic disorder characterized by poor mineralization, which affects the development of bones and teeth. More than 300 mutations in the ALPL gene associated with HPP have been identified. These mutations are associated with a wide range of disease severity. The most severe forms of the disorder tend to occur before birth and in early infancy. These infants have short limbs, an abnormally shaped chest, soft skull bones, poor feeding, failure to gain weight, respiratory complications, and high levels of calcium in the blood, known as hypercalcemia, which can lead to life-threatening complications. In other cases, the disease is not recognized until later in childhood, when it manifests as rickets, pain, decreased mobility, deficits of growth, and fractures. Children with less severe HPP can experience early loss of primary teeth and may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Findings in adults include a softening of the bones, known as osteomalacia, and recurrent fractures in the foot and thigh bones that can lead to chronic pain.