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Incidence

The prevalence of the severe form is estimated to be between 1 in 100,000 to 1 in 300,000. The prevalence of the milder forms is likely much more frequent. Hypophosphatasia has been reported worldwide in people of various ethnic backgrounds. This condition appears to be most common in white populations. It is particularly frequent in a Mennonite population in Manitoba, Canada, where about 1 in 2,500 infants is born with severe features of the condition. The severe forms of hypophosphatasia that appear early in life are inherited in an autosomal recessive pattern. Milder forms of hypophosphatasia can have either an autosomal recessive or an autosomal dominant pattern of inheritance.

Clinical Characteristics

This condition may present at various ages of onset. Onset can occur before birth or appear in adulthood. Perinatal HPP presents with clinical features noted at birth or before based on a prenatal ultrasound. Clinical exam will reveal obvious skeletal abnormalities including chest wall deformities, soft skull bones as well as short or bowed long bones. The skeleton is hypomineralized, which is readily identified on X-ray. Additional complications in infancy include poor feeding, a failure to gain weight, and respiratory problems. This form of HPP is almost universally fatal shortly after birth.
Infantile HPP is diagnosed by 6 months of age. Characteristic changes of rickets are seen on X-ray, and fractures are often present. Infants fail to grow appropriately, and some will experience vitamin B-6 responsive seizures. Hypercalcemia and nephrocalcinosis have also been described. Mortality in the infantile form of HPP is substantial.
Childhood HPP is diagnosed when disease manifests after 6 months of age. Children often have a delay in gross motor milestones and a static myopathy. A common feature of childhood HPP is premature loss of deciduous teeth (before 5 years of age) with the root intact. Radiographs reveal changes seen in rickets and often a radiolucent band extending from the growth plate into the metaphysis.
Adult HPP may manifest with recurrent or slow-to-heal metatarsal fractures or subtrochanteric femoral pseudofractures.
Odontohypophosphatasia, the least severe form of HPP, is diagnosed when dental abnormalities are present but no other skeletal disease, such as rickets or osteomalacia, is identified.
HPP is diagnosed based on the presence of one or more key clinical signs or symptoms along with a low blood level of alkaline phosphatase activity. The diagnosis should be confirmed with genetic testing for mutations in the ALPL gene.
The severe forms of hypophosphatasia that appear early in life are inherited in an autosomal recessive pattern. Milder forms of hypophosphatasia can have either an autosomal recessive or an autosomal dominant pattern of inheritance.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

HPP is diagnosed based on the presence of one or more key clinical signs or symptoms along with a low blood level of alkaline phosphatase activity and confirmed by genetic testing for mutations in the ALPL gene.