Hypophosphatasia

Hypophosphatasia

Alkaline phosphatase 47 IU/L (normal 100-300 IU/L)

CR – 1) Craniosynostosis with secondary findings of accentuated convolutional markings and enlarged sella tursica, 2) Metaphyseal flaring, irregular periphyseal regions with large “chewed out” metaphyseal lucencies, 3) Osteopenia with thin cortices, and 4) Mildly bowed tibias.

MR – Axial T2 images of the orbits show intraosseous invagination of cerebral tissue (related to increased intracranial pressure and osteomalacia).

Hypophosphatasia is related to insufficient tissue-nonspecific alkaline phosphatase which leads to the inability to process phosphate compounds. As a result, cartilage and osteoid mineralization is deficient. On laboratory evaluation, alkaline phosphatase is low and urinary phospoethanolamine is high.

Phenotypically, 4 variations of hypophosphatasia are known: perinatal, infantile, childhood and adult. Perinatal and infantile forms are autosomal recessive and often fatal related to respiratory insufficiency and myelophhthisic anemia. Childhood and adult forms are autosomal dominant and often present with extremity pain stiffness and weakness.

Perinatal form is characterized by severe lack of mineralization (even more pronounced than osteogenesis imperfecta). With the infantile form, metaphyseal demineralization predominates with a non-uniform rachitic pattern; localized “chewed out” segments of the metaphyses are a classic finding. Craniosynostosis is common with prominent convolutional markings and enlarged sella tursica. The adult pattern is similar to osteomalacia with coarsened trabeculae, Looser’s zones (although Looser’s zones are typically lateral in hypophosphatasia compared to osteomalacia where they are usually medial)and insufficiency fractures.

Shore RM. Metabolic Bone Disease. Caffey’s Pediatric Diagnositic Imaging. Mosby-Elsivier 11th Ed (2008).

Anne Oostendorp, MD