Juvenile Paget disease

Juvenile Paget disease is very rare disease which is known by many other names as well. These are

• Chronic congenital idiopathic hyperphosphatasemia
• Familial idiopathic hyperphosphatasemia
• Familial osteoectasia
• Hyperostosis corticalis deformans juvenilis
• Hyperphosphatasemia with bone disease
• Familial idiopathic hyperphosphatasia
• Idiopathic hyperphosphatasia
• Osteochalasia desmalis familiaris
• Osteoectasia with hyperphosphatasia

Juvenile Paget disease is a condition where there is an increase in bone turnover leading to bone  pain bony deformities.  This disease causes bones to  enlarge, deform and easily broken. The juvenile form of Paget’s disease is different from the adult Paget disease.

This condition is inherited in an autosomal recessive manner, which means both copies of the gene from each parent has to contribute.  The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene without showing signs and symptoms.

Known  gene locus is 8q24. The disease results from mutations or deletions in the TNFRSF11B gene. This mutation leads to osteoprotegerin which is inhibitor of  osteoclast differentiation and bone resorption.

This leads to increased osteoclast differentiation which in turn lead to increased bone resorption. Bone tissue is resorbed more quickly and in response the bone tissue that grows it is larger, weaker, and less organized than normal bone.

Juvenile Paget disease is a very rare condition and only about 50 people are affected till now worldwide.

Presentation

The patient with Juvenile Paget disease present in early childhood

• Bone pain and bone deformities [Bowed limbs]
• Failure to thrive.
• Dwarfism.
• Progressive enlargement of the head.
• Difficulty walking.
• Pigeon chest deformity.
• Muscular weakness.
• Premature shedding of the teeth.

These abnormalities become more severe during the adolescent growth spurt, when bones grow very quickly.

Thickening of the skull bones can lead to hearing loss. Deformation and collapse lead  to abnormal curvature of the spine.

Weight bearing long bones in the legs tend to bow and fracture easily.

Retinal degeneration  with or without angioid streaks,  renal stones and  internal carotid aneurysm are known associated findings

Investigations

Alkaline phosphatase  is raised. Urinary excretion of hydroxyproline is raised.

Enlargement and thickening of bones skull vault is noted on xrays.

Treatment

Healthy diet should be maintained for children.  Adequate physical activity should be maintained.

Bisphosphonates and calcitonin are associated with clinical, biological and radiological improvement.

Recombinant versions of osteoprotegerin are under research for managing this condition.

Complications

Following complications are know with Juvenile Paget Disease

• Bone pain
• Pathological fractures
• Kyphoscoliosis of spine
• Acetabular protrusion – protrusion of  acetabulum into the pelvis.
• Deafness
• Osteoporosis
• Delayed motor development

Prognosis

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