This disorder is characterized by the development and abnormally dense bones that are weak and can fracture easily. This is a congenital condition meaning affected people are born with it. The abnormally dense bone can affect the vital tissues and structures of the body resulting in serious problems such as compression of nerves in the skull causing vision loss and paralysis of facial muscles. When the crowding of the bone marrow occurs, it can result in the decreased level of blood cells necessary to fight off infections. There are two major forms of osteopetrosis; malignant infantile and adult. The infantile form, also known as autosomal recessive osteopetrosis, is a severe condition that can be evident at the birth of the infant reducing the life expectancy greatly. The adult form which is also known as autosomal dominant osteopetrosis is a milder form and may not be diagnosed until the person reaches adulthood.
Causes
There are around nine different genes that can contribute to the development of the condition. In around 75% of the cases, the genetic mutation identified in the gene is CLCN7 causing the autosomal dominant osteopetrosis. Around 50% of the cases develop because of a mutation in the TCIRG1 gene that causes autosomal recessive osteopetrosis. The genes involved in the development of this condition are important for the formation, function and the development of cells called osteoclasts. These cells are important for the process where the old bone is removed and is replaced with the new bones. This bone remodeling is important for the bones to remain strong. The genetic mutation results in the absence of abnormal osteoclasts and hence the new bone is formed but the old ones are not broken down. As the result, the bones appear to be unusually dense and structurally abnormal.
Symptoms
This condition is characterized by the abnormally dense bones present throughout the body. The symptoms can include low blood cell production, fractures, blindness from loss of cranial nerve function, deafness and facial paralysis. Among the infants with the autosomal recessive form, they may present an abnormally large head and hydrocephalus which is the accumulation of cerebrospinal fluid in the skull resulting in increased pressure on the brain tissue. Additional symptoms of this type can include involuntary rhythmic movements of the eyes, eyes that are crossed (strabismus), frequent infections such as pneumonia, delayed psychomotor development, abnormal enlargement of the liver and spleen and nerve compression. The autosomal dominant type is a milder form of the condition presenting hardening of some of the bones, fractures, abnormal enlargement of the liver and spleen, anemia and the development of blood cells outside the bone marrow.
Diagnosis
The diagnosis is based on an x-ray that shows unusually dense bones. Addition tests may also be required to detect the associated abnormalities with blood tests, vision tests, CAT scans and magnetic resonance imaging (MRI).
Treatment
The severe case is treated with a bone marrow transplant where the abnormal osteoclasts are replaced with the new ones. This treatment, however, does not reverse the damage that has already occurred.
References
https://www.niams.nih.gov/health_info/bone/additional_bone_topics/osteopetrosis.asp
https://ghr.nlm.nih.gov/condition/osteopetrosis#genes
https://rarediseases.info.nih.gov/diseases/4155/osteopetrosis
https://rarediseases.org/rare-diseases/osteopetrosis/
