Osteopetrosis is a rare congenital disorder (present at birth) in which the bones become overly dense. This results from an imbalance between the formation of bone and the breakdown of the bone. There are several types of osteopetrosis of varying severity. Symptoms can include fractures, frequent infections, blindness, deafness, and strokes. Osteopetrosis is also known as Albers-Schonberg Disease, Generalized Congenital Osteosclerosis, Ivory Bones, Marble Bones, Osteosclerosis Fragilis Generalisata
Types of osteopetrosis
- Malignant or infantile osteopetrosis
Infants are diagnosed with this form of osteopetrosis immediately or shortly after birth. This type of osteopetrosis is characterized by hematological difficulties, including anemia/thrombocytopenia/granulocytopenia. Compression of the cranial nerves leads to blindness and deafness. Other symptoms include pathological fractures and infections. It is genetically recessive. Infants with this form of osteopetrosis will most likely be referred for a bone marrow transplant. Sites in the United States of America known to have successfully transplanted osteopetrotic babies included St. Jude Children's Research Hospital in Memphis Tennessee, the Saint Louis Medical Center in St. Louis Missouri and . Without the bone marrow transplants, infants with this form of this disease generally die during the first ten years of life.
- Benign osteopetrosis
Benign osteopetrosis is genetically dominant, as opposed to the recessive transmission of malignant osteopetrosis. Generally, patients with benign osteopetrosis are diagnosed as adults and suffer from frequent fractures, which tend to have difficulties with healing. Life expectancy is not altered with this form of the disease. Other symptoms associated with benign osteopetrosis include osteomyelitis, pain, degenerative arthritis and headache. There are two recognized types of dominant osteopetrosis:
- Type I which is typified by (additional text to follow)
The site for the classical Albers-Schonberg disease has been identified to a site on chromosome 1 abbreviated as 1p21 by a group of Belgian scientists...
- Intermediate osteopetrosis
Because there are individuals with symptoms that do not fit clearly into the two more recognizable categories, some publications will present a third type of osteopetrosis known as intermediate osteopetrosis. These individuals will generally have a diagnosis in the first decade of life and symptoms more severe than those described as benign osteopetrosis, including blindness, deafness and hematological symptoms. There will be no family history of osteopetrosis, leading to the conclusion that this form is recessive. Research into this is being done at this time. There is some indication that this may be a more severe form of the dominant type of osteopetrosis and that benign osteopetrosis is not as benign as originally reported.
- Carbon Anhydrase Type II (CAII) Deficiency
This disease is caused by a deficiency of an enzyme, CAII, which has activity in bones, kidneys and the brain and all of these organs are therefore affected. It is rare and principally affects children of Mediterranean and Arab race. The gene responsible for producing CAII is found on chromosome 8 (at 8q22).
Symptoms in this type of osteopetrosis include increased bone density, a tendency to fracture easily and changes in body chemistry. Other symptoms may include intracranial calcifications, sensorineural hearing loss and developmental delays. The blood is slightly acidic and has a high chloride concentration (hyperchloraemic acidosis.) The blood acidity is caused by excessive leakage of bicarbonate from the kidney tubules (renal tubular acidosis). CAII must also have an important role in brain development and children who are affected often develop cerebral calcification and experience developmental delays.
This form of the disease usually causes symptoms in the first few years of life although x-rays are normal at birth. X-ray appearances often improve again in later life. Unlike malignant osteopetrosis, blood problems tend to be minor or absent.
This disease should be excluded in every child with osteopetrosis by measuring CAII activity.
Since starting this website in 1999, we have heard from many people with osteopetrosis, including one woman with the Transient . Some of them have chosen to remain anonymous and some of them can be found on the biography portion. We have found through discussion with many of these people, that osteopetrosis tends to comprise a very wide variety of symptoms and a broad spectrum of severity of these symptoms. The symptoms that we have seen are:
- Frequent fractures, especially of the long bones, which often do not heal
- Nerve compression, leading to headache, blindness, deafness
- Hematological difficulties, including anemic thrombocytopenia, leukopenia
- Enlarged spleen
- Frontal bossing of the skull
- Unusual dentition, including malformed and unerrupted teeth
Although it can be noted that all of these symptoms are discussed in the literature, the literature does not reflect how different these symptoms can be. For example, we have found people with fracture difficulties who do not have any hematological or neurological problems. We have also found individuals who present with the hematological issues, but not the osteomyelitis or fractures.
Normally, bone growth is a balance between osteoblasts (cells that create bone tissue) and osteoclasts (cells that destroy bone tissue). Sufferers of osteopetrosis have a deficiency of osteoclasts, meaning too little bone is being resorbed, resulting in too much bone being created.
The diagnosis of osteopetrosis is usually made when dense bones are discovered on x-rays. A bone biopsy can confirm the presence of the disease. Confirming the specific subtype of the disease is important so that individuals can receive the most appropriate treatment.
If untreated, infantile osteopetrosis usually results in death by the first decade of life due to severe anaemia, bleeding or infection. Adults with osteopetrosis are usually asymptomatic and have good long-term survival rates.
Various therapies have been used in the treatment of osteopetrosis. The US Food and Drug Administration (FDA) has approved Actimmune (interferon gamma-1b) for delaying disease progression in patients with severe malignant osteopetrosis. Actimmune is the only therapy approved specifically for the treatment of osteopetrosis. Adult and pediatric patients may benefit. In addition to the approved indication, there is also strong evidence to suggest that Actimmune reduces the chance for serious infection in osteopetrosis.
Bone marrow transplantation (BMT) allows the abnormal osteoclasts to be replaced with normal cells. BMT is the only approach that has resulted in a cure of the malignant infantile form of the disease. BMT replaces the abnormal osteoclasts with normal cells, curing the defect if the transplantation, or engraftment, is successful. Because of its high failure rate and because of its side-effects, BMT tends to be reserved for only the most severe cases of osteopetrosis. The survival rate after BMT in children with osteopetrosis is 40 to 70 % depending on how well matched the donor is to the patient. Young human leukocyte antigen-matched siblings provide marrow with the best chance for engraftment and cure of osteopetrosis.
High doses of Calcitrol (the active form of vitamin D) have been used to stimulate osteoclast function in individuals with osteopetrosis. Calcitrol has been shown to significantly reduce symptoms in people who have mild or severe forms of the disease, though it is not approved by the FDA for this purpose.
Large doses of glucocorticoid drugs (such as prednisone) may be given for short periods of time to patients with impaired red blood cell or platelet production. Prednisone improves blood counts in patients with anemia and low platelet counts and slows blood cell destruction. However, if continued for long periods, prednisone may reduce the growth velocity of children and predispose patients to infection.
Good nutrition is important to ensure normal growth and development of children with osteopetrosis. Physical and occupational therapy are also extremely useful in helping children to reach their full developmental potential. Even children with severe osteopetrosis frequently (about 80% of the time) have a normal intellectual level. The heavy skeleton results in gross motor delays. Blindness can delay speech. The average severely affected child walks at about 2 years and begins to speak at age 20 to 24 months.