Hypophosphatasia
Hypophosphatasia is clinically divided into three types, all caused by defects in the ALPL gene.
Hypophosphatasia, infantile (MIM 241500), is a severe form with onset in utero or before 6 months of age. Inheritance is autosomal recessive. Patients may have blue sclera, bowed short limbs, metaphyseal cupping, bone spurs of the ulna and fibula, poorly formed teeth, small thoracic cage with rachitic ribs, lack of skeletal ossification with fractures, craniosynostosis, skin dimples over the apex of long bone angulations and platyspondyly. Mental retardation or development delay may also be a feature. This disorder overlaps with osteogenesis imperfecta and achondrogenesis type IA. Laboratory abnormalities include: hypercalcemia, hypercalciuria, phosphoethanolaminuria, decreased tissue and serum alkaline phosphatase and mildly elevated phosphoethanolamine. Plasma and urine inorganic pyrophosphate may be elevated.
Hypophosphatasia, childhood (MIM 241510), has a more gradual and later onset. Inheritance is also autosomal recessive. Patients share many features with the infantile form including short stature, rachitic ribs, bowed legs, skin dimples and premature loss of teeth. They may also display craniostenosis, dolichocephaly, frontal bossing, proptosis and characteristic metaphyseal radiolucency. Presentation occurs beyond 6 months of age and there may be delayed onset of walking. Laboratory abnormalities include: low alkaline phosphatase, phosphoethanolaminuria and elevated plasma and urine inorganic pyrophosphate.
Hypophosphatasia, adult type (MIM 146300) presents in middle age and may actually be asymptomatic. Inheritance can be autosomal dominant or recessive with compound heterozygosity. Patients may suffer premature tooth loss, skeletal abnormalities, osteoporosis, recurrent fractures or long bone pseudofractures, with bowed legs, bone pain or arthropathy and chondrocalcinosis. Laboratory abnormalities are similar to those described under the childhood variant.
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