Contributor: Gordon K. Klintworth
Hypophosphatasia is an inherited autosomal recessive metabolic disease in which alkaline phosphatase is deficient in serum and tissue as a result of one of many mutations in the ALPL gene. Because pyrophosphate is not adequately metabolized it accumulates in certain parts of the body, including the synovial fluids of joints. The disease was first described in 1948 by Rathbun et al. Heterozygotes can be recognized by a low serum alkaline phosphatase. Alkaline phosphatase is normal in the intestine and placenta but very low in bone, kidney, liver and plasma. Three varieties of hypophosphatasia are recognized: hypophosphatasia - type I, hypophosphatasia - type II, and hypophosphatasia - type III. All forms may be allelic.