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.
Hypophosphatasia perinatal type (neonatal hypophosphatasia)
Hypophosphatasia infantile type (phosphoethanolaminuria)
Hypophosphatasia childhood type
Hypophosphatasia adult type (mild hypophosphatasia)
Inborn error of metabolism initially identified by Rathbun
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
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
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.
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.
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.
Check serum calcium level and renal
function. Assess extent of skeletal abnormalities.
Care should be taken with positioning
for surgery to ...