Hypophosphatasia

Hypophosphatasia Fact Sheet
Dan Boboia, DDS


What is it?

A rare inborn error of metabolism characterized by a wide spectrum of defects in mineralized tissues. Patients can have a low serum alkaline phosphatase level, excessive excretion of phosphoethanolamine in the urine, and abnormally wide osteoid arms. Clinical manifestations are highly variable and range from almost a total lack of skeletal formation to the premature loss of permanent anterior teeth.

Epidemiology:

Inherited as autosomal recessive trait with a prevalence of 1:100,000 live births

Etiology:

Caused by a defect in the gene encoding tissue nonspecific alkaline phosphatase (TNSALP)

Enzyme is present in most tissues and in blood serum; it cleaves phosphate from three other specific proteins. These proteins are intermediates in diverse and unrelated biochemical pathways.

Signs and Symptoms / Diagnosis:

Classified according to age when symptoms first appear

1) Perinatal - occurs in utero; most infants are stillborns or die shortly after birth; death is usually due to respiratory failure; marked hypocalcification of skeletal structures is often observed

2) Infantile – patients may appear normal up to 6 months of age-after this they may show failure to grow; less severe yet similar skeletal deformities as the lethal form; infants feed poorly, present with rib deformities (predisposing to pnemonia), skull deformities such as wide or obliterated fontenelles / cranial sutures (predisposing to increased intracranial pressure), blue sclera and pathologic lid retraction; generalized osteopenia and ossification defects with a bowing of the long bones; fatal in about half of cases

3) Childhood - child may have rickets, small stature, waddling gate, improperly formed periodontal ligament due to partial or complete lack of cementum formation; premature loss of primary anterior teeth (without evidence of a significant inflammatory response) displaying cementum aphasia; deciduous incisors usually effected first; Skull has radiographic appearance of “beaten copper” showing uniformly spaced, poorly defined, small radiolucencies

4) Adult – typically mild; associated with premature loss of anterior maxillary and mandibular teeth, history of early primary tooth loss, enamel hypoplasia, proptosis, elevated intracranial pressure / brain damage, pseudogout, and stress fractures involving the metatarsal bones of the feet



Treatment and Prognosis:

Treatment of symptoms is all that can be done because the lack of alkaline phosphatase cannot be corrected. Attempts to treat this condition by alkaline phosphatase infusions have been unsuccessful because the enzyme function intracellularly rather than in the extracellular environment. Fractures are treated with orthopedic surgery, prosthetic appliances are indicated to replace missing teeth, but satisfactory results are not always attainable because of the hypoplastic alveolar bone.