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

Epidemiology

This is an extremely rare condition.

Presentation

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 teeth.³

Associated diseases

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

Investigations

• 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.

Differential diagnosis

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

Management

• 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 anti-resorptive drugs, such as the bisphosphonates, e.g. pamidronate or calcitonin, has 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

Complications

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

Prognosis

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

Document references

1. Ralston SH, Langston AL, Reid IR; Pathogenesis and management of Paget's disease of bone. Lancet. 2008 Jul 12;372(9633):155-63. [abstract]
2. Golob DS, McAlister WH, Mills BG, et al; Juvenile Paget disease: life-long features of a mildly affected young woman. J Bone Miner Res. 1996 Jan;11(1):132-42. [abstract]
3. Juvenile Paget Disease, Online Mendelian Inheritance in Man (OMIM)
4. Hofbauer LC, Schoppet M; Osteoprotegerin deficiency and juvenile Paget's disease. N Engl J Med. 2002 Nov 14;347(20):1622-3; author reply 1622-3.
5. Ralston SH; Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):101-11. [abstract]
6. Allen CA, Hart BL, Taylor CL, et al; Bilateral cavernous internal carotid aneurysms in a child with juvenile paget disease and osteoprotegerin deficiency. AJNR Am J Neuroradiol. 2008 Jan;29(1):7-8. Epub 2007 Oct 18.
7. Silve C; Hereditary hypophosphatasia and hyperphosphatasia. Curr Opin Rheumatol. 1994 May;6(3):336-9. [abstract]
8. Tuysuz B, Mercimek S, Ungur S, et al; Calcitonin treatment in osteoectasia with hyperphosphatasia (juvenile Paget's disease): radiographic changes after treatment. Pediatr Radiol. 1999 Nov;29(11):838-41. [abstract]
9. Cundy T, Wheadon L, King A; Treatment of idiopathic hyperphosphatasia with intensive bisphosphonate therapy. J Bone Miner Res. 2004 May;19(5):703-11. Epub 2004 Jan 19. [abstract]
10. Cundy T, Davidson J, Rutland MD, et al; Recombinant osteoprotegerin for juvenile Paget's disease. N Engl J Med. 2005 Sep 1;353(9):918-23. [abstract]
11. Skowronska-Jozwiak E, Lorenc RS; Metabolic bone disease in children : etiology and treatment options. Treat Endocrinol. 2006;5(5):297-318. [abstract]