Juvenile Paget's Disease

Synonyms: chronic congenital idiopathic hyperphosphatasemia, familial idiopathic hyperphosphatasia, familial osteoectasia, hereditary hyperphosphatasia, hyperostosis corticalis deformans juvenilis

There is generalised increase in bone turnover leading to widespread bony deformities in childhood with bone pain.¹ Some patients may have milder forms.^2,3

The juvenile form of Paget's disease is different from the adult form. It is autosomal recessive, with gene locus 8q24 and results from mutations or deletions in the TNFRSF11B gene.³ These lead to a deficiency of osteoprotegerin a member of the TNF-receptor superfamily.⁴ Osteoprotegerin inhibits osteoclast differentiation and bone resorption.⁵

This is an extremely rare condition.

Presentation is in early infancy with:

• Bone deformity with pain
• Failure to thrive
• Dwarfism
• Progressive enlargement of the head
• Bowed limbs
• Difficulty walking
• Pigeon breast deformity
• Muscular weakness
• Premature shedding of the teeth³

• Retinal degeneration (±angioid streaks)
• Recurrent renal colic from calcium containing stones
• Internal carotid aneurysms (one case report)⁶

• Blood tests - reveal raised alkaline phosphatase (ALP)
• Urine - raised hydroxyproline
• Plain x-rays - there is enlargement and thickening of bones e.g. the skull vault

• Rickets
• Osteomalacia
• Other genetic bone disorders e.g. Familial expansile osteolysis

• Children need to be advised on a healthy diet with adequate calcium and vitamin D intake. This should be combined with physical activity regimens where possible.
• The use of antiresorptive drugs, such as the bisphosphonates, e.g. pamidronate or calcitonin, have led to clinical, biological and radiological improvement.^5,7,8
• Some work suggests the use of intensive bisphosphonate therapy, but this may lead to osteopetrosis.^5,9
• Recombinant versions of osteoprotegerin are under research.¹⁰

• Bone pain
• Pathological fractures
• Kyphoscoliosis
• Acetabular protrusion
• Sensorineural deafness
• Osteoporosis
• Delayed motor development¹¹

Severity of the disease increases as the child progresses towards adolescence. Some patients will survive beyond the age of 50 years.