Clinical Practice Guidelines for Hypophosphatasia

Hypophosphatasia (HPP) is an inherited skeletal disease caused by defects in tissue-nonspecific alkaline phosphatase (TNSALP). Reduced serum alkaline phosphatase (ALP) activity despite demonstration of impaired mineralization of bones and rickets-like changes on bone X-ray scans is a characteristic of this disease (1, 2). Due to the loss of TNSALP activity, its substrates, such as phosphoethanolamine (PEA), inorganic pyrophosphate, and pyridoxal 5’-phosphate (PLP), are not degraded and, therefore, accumulate in the body. The disease is transmitted as an autosomal recessive trait in many families and as an autosomal dominant trait in some families. The incidence of severe HPP in Japan is estimated to be 1 out of 150,000 people (3, 4). The frequencies of other forms of HPP are unclear, and there may be undiagnosed cases. Clinical symptoms vary with age and severity, and the disease is usually classified into 6 clinical disease forms (perinatal severe [lethal], perinatal benign, infantile, childhood, adult, and odontohypophosphatasia) (5, 6), but other classification methods are also used. Findings on plain bone X-ray scans include generalized hypomineralization of bones, deformity of long bones, and metaphyseal irregularity (Fig. 1). Symptoms including convulsions, hypercalcemia, poor weight gain, and premature loss of deciduous teeth are also observed. Open in a separate window Fig. 1. X-ray images of pediatric patients with hypophosphatasia (HPP). (A) Bone X-ray image of perinatal lethal HPP. Marked hypomineralization of all bones in the body, including the cranium, vertebrae, and long bones, and deformation of long bones are observed. Rickets-like metaphyseal irregularity is noted. The thorax is small, and respiratory disorder is inevitable. (B) Bone X-ray image of perinatal benign HPP. Hypomineralization is very minimal, and no metaphyseal irregularity is noted. Long bones are deformed. Bone spurs are noted sporadically.