Specialty medical genetics ICD-9-CM 756.52 DiseasesDB 9377 | ICD-10 Q78.2 OMIM 166600 259700 eMedicine med/1692 | |
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Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle, or osteomalacia, in which the bones soften. Osteopetrosis can cause bones to dissolve and break.
Contents
It can cause osteosclerosis. The cause of the disease is understood to be malfunctioning osteoclasts. Radiological findings will show a bone-in-bone appearance.
Signs and symptoms
Despite this excess bone formation, people with osteopetrosis tend to have bones that are more brittle than normal. Mild osteopetrosis may cause no symptoms, and present no problems. However, serious forms can result in stunted growth, deformity, and increased likelihood of fractures; also, patients suffer anemia, recurrent infections, and hepatosplenomegaly due to bone expansion leading to bone marrow narrowing and extramedullary hematopoiesis. It can also result in blindness, facial paralysis, and deafness, due to the increased pressure put on the nerves by the extra bone.
Pathogenesis
Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (breakdown of bone matrix) by osteoclasts. In osteopetrosis, the number of osteoclasts may be reduced, normal, or increased. Most importantly, osteoclast dysfunction mediates the pathogenesis of this disease.
Osteopetrosis is caused by underlying mutations that interfere with the acidification of the osteoclast resorption pit, for example due to a deficiency of the carbonic anhydrase enzyme encoded by the CA2 gene. Carbonic anhydrase is required by osteoclasts for proton production. Without this enzyme hydrogen ion pumping is inhibited and bone resorption by osteoclasts is defective, as an acidic environment is needed to dissociate calcium hydroxyapatite from the bone matrix. As bone resorption fails while bone formation continues, excessive bone is formed.
Differential diagnosis
The differential diagnoses include other disorders which can cause diffuse osteosclerosis, such as hypervitaminosis D and hypoparathyroidism, Paget's disease, diffuse bone metastasis of breast or prostate cancer (which tend to be osteoblastic, while most metastases are osteolytic), intoxication with fluoride, lead or beryllium, and hematological disorders such as myelofibrosis, sickle cell disease, and leukemia.
Treatment
The only durable cure for osteopetrosis types affecting the osteoclasts is a total bone marrow transplant.
If complications occur in children, patients can be treated with vitamin D. Gamma interferon has also been shown to be effective, and it can be associated to vitamin D. Erythropoetin has been used to treat any associated anemia. Corticosteroids may alleviate both the anemia and stimulate bone resorption. Fractures and osteomyelitis can be treated as usual.
Prevalence
Worldwide, there is 1 affected newborn out of every 20,000 to 250,000, but the odds are greater in the Russian region of Mari El (1 of every 14,000 newborns) and much greater in Chuvashia (1 of every 3,500—4,000 newborns) due to genetic features of the Mari people and Chuvash people, respectively.