At a Glance

Osteopetrosis, or marble bone disease, is a rare congenital disease caused by any of several gene defects that affect the differentiation or function of osteoclasts.

It should be considered in any newborn relative of a proband. Otherwise, it is so rare (<1/10,000 live births, even in areas reporting the disease most frequently) that a primary test and/or newborn screening is not indicated; conversely, with failure to thrive or visual defects in the newborn, the possibility of osteopetrosis should be considered.

Less severe forms are diagnosed in older children and adolescents. Children and adolescents with less severe forms do not have short stature, since bone growth is maintained by growth plates. The diagnosis is often made after a fracture or after an incidental finding on a complete blood count (CBC), showing evidence of extramedullary hematopoiesis.

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Occasionally the diagnosis of mild osteopetrosis is made in an asymptomatic adult, typically after a plain X-ray. The adult does not need treatment; treatment is more dangerous than the disease. However, it may be indicated to determine the genetic cause for genetic counseling of families.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The diagnosis of osteopetrosis is usually made using imaging studies; computed tomography (CT) of skull or long bones will show dense bone in regions normally containing marrow.

In severe cases, there may also be hepatosplenomegaly with extramedullary hematopoiesis. In these cases, nucleated red blood cells and decreased hematocrit will be seen on CBC.

Bone biopsy should be done before therapy can be considered, including possible bone marrow transplant.

Otherwise, routine laboratory testing is usually not indicated to diagnose osteopetrosis.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

There are no known acquired or secondary causes of osteopetrosis.

What Lab Results Are Absolutely Confirmatory?

In vitro differentiation from blood monocytes and identification of the affected gene are possible, but are largely research tools. About 60% of cases have defects in ATPA3 or CLCN7 that can be determined by sequencing. Several other genes are occasionally found defective. Generally, these can only be done by referral to academic centers specializing in osteopetrosis research; at present, the tests are not available commercially.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Any case requiring treatment should be referred to a highly specialized center at which options, including bone marrow transplant, may be available. The family should be advised that transplant therapy has considerable risk, except in the rare instance of a perfect transplant match from an identical twin. This is a consideration when osteopetrosis is diagnosed in older children or adolescents, when transplant has about 50% 1 year mortality. In severe infantile osteopetrosis, transplant is the only option with a chance of long-term survival.