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Inherited inborn error of metabolism characterized by severe bone disease (similar to vitamin D-resistant rickets), failure to thrive, movement disorders, and low plasma levels of alkaline phosphatase.

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Hypophosphatasia perinatal type (neonatal hypophosphatasia)

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Hypophosphatasia infantile type (phosphoethanolaminuria)

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Hypophosphatasia childhood type

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Hypophosphatasia adult type (mild hypophosphatasia)

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Odontohypophosphatasia

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Inborn error of metabolism initially identified by Rathbun in 1948.

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Estimated at 1:100,000 live births (and 1 carrier per 200 individuals in the United States). Some ethnic or religious groups have a higher incidence of the disease (1:2500 among Canadian Mennonites). No sex predilection.

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Autosomal recessive. However, mild adult hypophosphatasia and odontohypophosphatasia cases seem to be inherited as an autosomal dominant trait. Prenatal diagnosis is possible by measuring alkaline phosphatase activity in chorionic villus samples from amniocentesis, and the perinatal (severe) form of the disease can be detected by ultrasonography. The defective gene, called ALPL, is located at 1p36.1-34.

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Deficient activity of tissue-nonspecific alkaline phosphatase, one of the four isomers of alkaline phosphatase (each of which has its own gene locus). This results in accumulation of several metabolites including phosphoethanolamine, pyridoxal-5′-phosphate (a form of vitamin B6), and inorganic pyrophosphate, which are found in large amounts in the blood and urine. The characteristic defective calcification of bones in children (rickets) and adults (osteomalacia) is caused by the accumulation of inorganic pyrophosphate.

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Clinical features. Radiologic appearance: epiphyseal and metaphyseal abnormalities of long bones, vertebrae, and ribs. Elevated plasma and urine levels of phosphoethanolamine. Elevated plasma inorganic pyrophosphate and pyridoxal-5′-phosphate.

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Hypophosphatasia varies widely in clinical presentation. It has been subdivided into five categories: perinatal, infantile, childhood, adult, and odontohypophosphatasia. The earlier the symptoms occur, the more severe the disease. Perinatal form presents with a history of poor feeding, failure to thrive, hypotonia, and skin-covered spurs extending from the forearms or legs; it is lethal in 50% of cases. Childhood form often presents as delayed walking, early loss of deciduous teeth, and bone pain. Adult form has mild symptoms (foot pain as a result of spontaneous fractures of metatarsal bones). Odontohypophosphatasia is limited to dental problems (premature loss of adult teeth). Severe forms are characterized by widespread failure of ossification of the skeleton and marked shortening of long bones. Multiple rib fractures may lead to flail chest and predispose to pneumonia. There may be failure of ossification of the cranial vault. Hypercalcemia may lead to nephrocalcinosis and renal failure. In milder childhood forms, the skeletal abnormalities are less severe, but frequent fractures and bone pain are typical. There is defective development of the teeth leading to premature loss. There is no effective treatment, but some spontaneous improvement may occur as the child ages.

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Check serum calcium level and renal function. Assess extent of skeletal abnormalities.

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Care should be taken with positioning for surgery to ...

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