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Hereditary hyperphosphatasia

Last revised by Daniel J Bell on 10 Feb 2020

Hereditary hyperphosphatasia, also known as juvenile Paget disease, is an autosomal recessive osteopathy due to osteoprotegerin deficiency which has a similar clinicoradiological presentation to adult Paget disease of bone.

The term "hyperphosphatasia" has been used to describe a heterogeneous group of bone disorders characterized by elevated serum alkaline phosphatase due to a generalized increase in bone remodeling 2.

The prototypic but not sole member of this group is known by various names including most specifically juvenile Paget disease but also referred to as congenital hyperphosphatasia, idiopathic hyperphosphatasia, chronic congenital idiopathic hyperphosphatasia, chronic familial hyperphosphatasia, familial idiopathic hyperphosphatasia, familial osteoectasia, osteoectasia with hyperphosphatasia, chronic progressive osteopathy with hyperphosphatasia, and hyperostosis corticalis deformans juvenilis 2-4

Onset of disease is after 2 years of age. Fever, pain, gradual skull enlargement and pathologic fractures are seen in these patients. Serum alkaline phosphatase levels are high.

Normally, osteoprotegerin is a decoy receptor for receptor activator of nuclear factor-κB (RANK) ligand, thereby suppressing osteoclast differentiation. In this disorder, osteoprotegerin is deficient, resulting in osteoclast overactivity and thus rapid bone turnover and remodeling 3.

Homozygous or compound heterozygous mutations in TNFRSF11B, on chromosome 8q24.2, results in deficiency of the gene product, osteoprotegerin 3.

It resembles adult Paget disease of bone but involves the whole skeleton and presents in children.

Bone density is reduced with coarsened trabecular pattern. Specific findings vary by body site:

  • skull: widened diploic spaces and patchy sclerosis
  • long bones: expanded diaphyses, bowing, short stature
  • spine: biconcave vertebrae with height loss
  • pelvis/hips: coxa vara and protrusio acetabuli

A bone scan demonstrates a superscan due to widespread osteoblastic activity.

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