Hypophosphatasia is a rare genetic bone disorder characterized by osteoblast hyperactivity and bone remodeling with loss of, or incomplete, mineral deposition. It is comparable to osteomalacia and rickets, but maintains a unique set of characteristic identifiers (Mornet 2008; Brickley and Ives 2008). Also called, Rathbun’s Syndrome, hypophosphatasia can be autosomal dominant or autosomal recessive depending on the individual. Severe forms are usually transmitted as autosomal recessive with a recurrence risk of 25 percent, while milder forms can be transmitted as either autosomal dominant or autosomal recessive, with between 25-50 percent recurrence rates (Mornet 2008). Hypophosphatasia has an incidence rate of 1 in 100,000 live births (Brickley and Ives 2008; Wendling et al. 2001). In half of all cases, the condition is fatal.
Mutations within the liver/bone/kidney alkaline phosphatase gene (ALPL) that encodes for tissue non-specific alkaline phosphatase (TNAP) inhibits the mineralization of bone by causing a deficiency of TNAP (Mornet 2008). Regularly, TNAP is dephosphorylated and the inorganic phosphate that is knocked off is used for hydroxyapatite crystallization. If inorganic pyrophosphates (PPi), which are formed when ATP is hydrolyzed into AMP, are not dephosphorylated by TNAP, then hydroxyapatite deposition is inhibited (Mornet 2008).
There are six forms of hypophosphatasia recognized: perinatal lethal; infantile; childhood; adult; odontohypophosphatasia; and perinatal benign. In the first form in utero osteochondral spurs can form on the fore arms and legs (Mornet 2008). The fetus is unable to make it to term and is aborted within few days. The perinatal benign form often shows change in the formation of the spurs but develop short limbs with bowing and dimples covering the long bones (Wendling et al. 2001).
Infantile hypophosphatasia presents with open fontanels and premature ossification of cranial sutures (Mornet 2008). Bone pain and fractures are also common. The childhood form of the disorder results in enlarged joints, delayed on-set of walking with waddling, shortness of stature, and the formation of a dolichocephalic skull where the skull develops longer than normally proportional to its width (Mornet 2008; Wendling et al. 2001).The adult form of hypophosphatasia occurs during middle age foot pains, where stress fractures of the metatarsals frequently occur, are usually the first areas to signal onset (Wendling et al. 2001). Later development of pseudofractures of the long bones can cause bad pain. This is usually experienced worse in the femora.
Odontohypophosphatasia can affect bot children and adults and is characterized by fully rooted primary teeth being revealed (Mornet 2008). The anterior deciduous teeth are most likely to be affected. Dental x-rays show reduced alveolar bone enlarged pulp chambers and root canals.
The chest may develop abnormalities and if the distortions are severe enough, pneumonia can result...