congenital hypophosphatasia

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Hypophosphatasia refers to a rare metabolic disorder characterized by deficient serum alkaline phosphatase activity. The effects of hypophosphatasia are primarily seen in the skeletal system. The condition has marked variation in clinical expression (see subtypes).

Epidemiology

The true incidence is uncertain as it is thought many people may live with mild forms of the disease without being diagnosed. Some authors have estimated its prevalence at 1 in 100,000. It can display either autosomal dominant or recessive inheritance, which complicates genetic counseling.

Clinical presentation

Complications

Complications are primarily those of hypercalcemia.

Pathology

The underlying genetic abnormality is almost exclusively due to a mutation in the ALPL gene that encodes for tissue non-specific alkaline phosphatase (TNSAP) enzyme. This results in defective bone mineralization and extracellular accumulation of TNSAP substrates. With over 300 different specific mutations recognized, the severity of the resultant clinical disorder depends on the degree to which TNSAP activity is impaired. The severer the impairment, the earlier the presentation.