- What is osteopetrosis?
- What are the 2 types osteopetrosis?
- How is osteopetrosis diagnosed?
- How many people have osteopetrosis?
- If osteopetrosis is so rare, why should you care?
Osteopetrosis, also known as Marble Bone Disease or Albers-Schonberg disease, is an extremely rare, inherited disorder caused by mutations on the CLCN7 gene whereby the bones harden, becoming denser.
Bone growth is a balance between osteoblasts (cells that create new bone tissue) and osteoclasts (cells that destroy old bone tissue). Sufferers of osteopetrosis have impaired osteoclasts function; meaning old bone tissue is not destroyed and removed from the body. This results in bones that are denser and more brittle than normal bones. Mild forms of osteopetrosis may cause no symptoms and present no problems; however, more severe forms can result in stunted growth, deformity, increased likelihood of fractures, bone infection, enlarged spleen, kidney problems, anemia, and other blood issues. Osteopetrosis can also lead to blindness, facial paralysis, and deafness; due to the increased pressure put on the nerves by the extra bone.
What are the 2 types of osteopetrosis?
There are two types of osteopetrosis; a genetically dominant form called Autosomal Dominant Osteopetrosis and a genetically recessive form called Autosomal Recessive Osteopetrosis (ARO). Each of us carries two copies of the CLCN7 (chloride channel 7) gene (one from the mother and one from the father). Autosomal Dominant Osteopetrosis occurs when a person receives one mutated (or “bad”) CLCN7 gene from one parent and one normal CLCN7 gene from the other parent. Likewise, Autosomal Recessive Osteopetrosis occurs when a person receives two copies of the mutated CLCN7 gene; one copy from each parent.
- Autosomal Dominant Osteopetrosis (ADO)
- As mentioned, ADO occurs when a person inherits one copy of the mutated CLCN7 gene from their mother or father. The severity of ADO varies tremendously, even among people with the same mutation in the same family. One third of people with the mutated CLCN7 gene will be entirely disease free, but have a 50/50 chance of passing the mutated gene onto each of their children. We call these people carriers. The other two thirds with the mutated CLCN7 gene can have either mild, moderate, or severe forms of ADO. The dominant form of osteopetrosis does not typically alter life expectancy, but can significantly reduce quality of life due to the symptoms that are associated with the disease. Symptoms include, but are not limited to: osteomyelitis (bone infection); bone pain; degenerative arthritis; frequent fractures; nerve compression that can lead to blindness, deafness, or stroke; and hematological problems that can lead to spleen enlargement, liver damage, anemia, and bleeding. Many ADO patients (especially those with mild or moderate forms of the disease) are not diagnosed until adulthood because they do not experience any symptoms as children or adolescents and have no reason to be tested. Furthermore, there may be many cases of ADO that are undiagnosed or misdiagnosed due to the general population’s lack of knowledge about ADO.
- Autosomal Recessive Osteopetrosis (ARO)
- ARO is also known as Malignant Infantile Osteopetrosis because it is diagnosed immediately or shortly after birth and is fatal if left untreated. As stated, ARO occurs when a person inherits two copies of the mutated CLCN7 gene from their parents. A person with ARO is born with extremely brittle bones and 75% of those afflicted will develop hematological problems such as, anemia, thrombocytopenia, and granulocytopenia in their first year of life. Compression of the cranial nerves in ARO patients often leads to blindness and deafness and other symptoms include frequent bone fractures, infections, and low calcium levels that may cause seizures. A bone marrow transplant is the only known treatment for ARO and without treatment most ARO patients will not live past the age of ten.
How is osteopetrosis diagnosed?
Osteopetrosis can be diagnosed in two ways: through skeletal x-rays and through genetic testing of the CLCN7 gene.
- X-ray Diagnosis
- Osteopetrosis is most commonly diagnosed through skeletal x-rays. X-rays of osteopetrosis patients will have an unusual density with a chalky white appearance. Bone density tests and bone biopsies can confirm the diagnosis while other tests such at CAT scans or MRI can be performed to evaluate any potential complications.
- Genetic Testing Diagnosis
- Osteopetrosis can also be diagnosed through genetic testing of the CLCN7 gene. Genetic testing can be especially useful if a person would like to know whether they are a carrier of the mutated CLCN7 gene. Remember that carriers are the one in three people who have a mutated CLCN7 gene, but are disease free. Genetic testing is the only way to determine whether a person is a carrier and, thus, if a person has a 50/50 chance of passing the mutated gene to each of their children.
How many people have osteopetrosis?
The less severe form, Autosomal Dominant Osteopetrosis, affects approximately 1,250 people in the United States. Autosomal Recessive Osteopetrosis, or Malignant Infantile Osteopetrosis, is even rarer, affecting only 8 to 40 children born in the United States each year. It is difficult to estimate how often the different forms of osteopetrosis occur worldwide. The disease could be much more prominent, but lack of communication and knowledge of the disease could affect documentation of this disease.
If osteopetrosis is so rare, why should you care?
As we mentioned before, normal bone growth is a balance between osteoblasts (cells that create new bone tissues) and osteoclasts (cells that destroy old bone tissue). In osteopetrosis the osteoclasts do not function properly and old bone tissue is not being destroyed and removed from the body. It is the mission of the International Osteopetrosis Association (IOA) to fund research specific to studying osteoclasts function. In understanding how these cells function, we may be able to find answers to a whole host of other bone mineralization disorders - such as osteoporosis – to name just one!
The International Osteopetrosis Association is a not-for-profit organization recognized as tax-exempt under Internal Revenue Code section 501(c)(3). 