Osteopetrosis: A Congenital Disease

Armen Hareyan's picture

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.

Osteopetrosis is a congenital disease characterized in each of its forms by defective osteoclast function. Osteoclasts are the cells responsible for bone resorption. They are necessary for the formation of bone marrow. In people with osteopetrosis, osteoclasts do not function normally and the cavity for bone marrow does not form. This causes bones that appear dense on x-ray and cannot resist average stressors and therefore break easily. The condition is quite rare; incidences have been reported at 1 in 20,000-500,000 for the dominant form and 1 in 200,000 for the recessive form.

Among the difficulties in diagnosing and being treated for this disease and its symptoms are the realities that there are at least two and as many as five differently recognized types of osteopetrosis.

Osteopetrosis is generally 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.

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:


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.

Symptoms common to Osteopetrosis

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: