$Unique_ID{BRK04073} $Pretitle{} $Title{Osteopetrosis} $Subject{Osteopetrosis Albers-Schonberg Disease Melorheistosis Osteopoikilosis Osteogenesis Imperfecta} $Volume{} $Log{} Copyright (C) 1987, 1990 National Organization for Rare Disorders, Inc. 354: Osteopetrosis ** IMPORTANT ** It is possible the main title of the article (Osteopetrosis) is not the name you expected. Please check the SYNONYMS listing to find the alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Albers-Schonberg Disease Osteosclerosis Fragilis Generalisata Generalized Congenital Osteosclerosis Ivory Bones Marble Bones Information on the following diseases can be found in the Related Disorders section of this report: Melorheistosis Osteopoikilosis Osteogenesis Imperfecta General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Osteopetrosis is a combination of several rare genetically caused symptoms grouped together as one disorder. It can be inherited as either a dominant or recessive trait and is marked by increased bone density, brittle bones, and in some cases, skeletal abnormalities. Although symptoms may not initially be apparent in people with mild forms of this disorder, trivial injuries may cause bone fractures due to abnormalities of the bone. The dominantly transmitted form is milder than the recessive form of Osteopetrosis, and may not be diagnosed until adolescence or adulthood when symptoms first appear. More serious complications occur in the recessive form which may be diagnosed from examination of skeletal x-rays during infancy or childhood. Symptoms Initial symptoms of the dominant form of Osteopetrosis may include bone fractures caused by trivial injuries, and unusual dental problems. Bone pain may occur in the spine, and cranial nerves may be affected. Some vision defects or facial palsy may also be symptomatic of the dominant form of Osteopetrosis. Severe anemia may occur due to obliteration of the bone marrow. A more serious recessive form of Osteopetrosis is present at birth and can be diagnosed by skeletal x-rays. Symptoms may include retardation of growth, enlargement of the head, a deformity of the base of the skull and delayed closure of the soft spot on the skull of infants with this disorder. Vision failure or cataracts, deafness, dental decay, chest deformity and brain damage are also symptomatic of the more severe form of Osteopetrosis. Bone defects may involve increased density of many bones including vertebrae, ribs, long bones, the pelvis and the skull. Concurrently there is a decrease in density of the bone marrow in people affected by this disorder. Causes Osteopetrosis can be inherited as either a dominant or recessive trait. The basic defect in bone growth involves an insufficient production of intercellular bone tissue by cells called osteoblasts. These osteoblasts aid in the production of bone by maintaining a balance between formation and loss of calcium (resorption) in the bone. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal. Affected Population Osteopetrosis occurs in children and lasts throughout life. The dominant form (which is milder than the recessive form) may be present in childhood, but not diagnosed until adolescence or adulthood. Both forms of this disorder affect males and females in equal numbers. Osteopetrosis is very rare. Related Disorders Melorheistosis is a rare disorder characterized by shortening or deformity of one or more limbs due to a problem with calcium density in bones. It is inherited as a dominant trait. Pain and limitation of movement of the affected arm(s) or leg(s) is usually present. The prognosis for this disorder is guardedly favorable. Osteopoikilosis, also known as "spotted bones", is a rare disorder which may occur in conjunction with melorheostosis. Usually without apparent symptoms, Osteopoikilosis may be discovered during X-ray examination for other bone growth disorders. Symptoms usually occur most often between the ages of fifteen and sixty. Spotty shadows appear on x-rays of wrist and ankle bones, finger or toe bones, long bones, pelvis, skull, and/or ribs (spinal bones exempted). These spots are less than one centimeter in diameter and usually of uniform density. Bone growth nodules can grow larger or diminish and disappear. Osteogenesis Imperfecta, or "brittle bone disease", is a group of hereditary connective tissue disorders characterized by unusual bone fragility and tendency to fracture. Traditionally the disease has been recognized in two forms. Osteogenesis Imperfecta Congenita is apparent at birth, while Osteogenesis Imperfecta Tarda manifests itself only later, usually at three or four years of age. OI Tarda tends to be a milder form of the disease. Both forms of Osteogenesis Imperfecta affect 1 in 20,000 to 50,000 births in the United States. (For more information on this disorder, choose "osteogenesis imperfecta" as your search term in the Rare Disease Database.) Therapies: Standard Treatment of Osteopetrosis is symptomatic and supportive. Physical therapy may be of benefit in some cases. Genetic counseling can be of assistance for families in which this disorder occurs. Therapies: Investigational Experimental treatment of Osteopetrosis includes bone marrow transplantation. Bone marrow is found inside the bone and produces white blood cells, red blood cells, or clotting cells (platelets). The transplant procedure involves extracting cross-matched bone marrow from a healthy donor and injecting it intravenously into a patient. The healthy marrow cells enter the general circulation and migrate through the blood to marrow cavities in the patient's bones. The new marrow cells begin to grow and produce new white blood cells, red blood cells, and platelets. The procedure involves risks which must be balanced against possible benefits, and is used experimentally in the most severe cases of Osteopetrosis. The most serious cases of Osteopetrosis are also being treated experimentally with a combination of steroids (prednisone) and a low calcium, high phosphate diet. Another alternative treatment is the administration of calcitriol, the biologically active form of vitamin D. High doses of this drug, which stimulates bone-resorbing cells called osteoclasts, improved bone turnover in patients on whom it was studied, and it increased formation of blood cells. In one patient disease symptoms were reversed almost completely, but more research is needed to determine long-term safety and effectiveness of the experimental therapies. This disease entry is based upon medical information available through January 1990. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Osteopetrosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse Box AMS Bethesda, MD 20892 (301) 495-4484 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 The Paget's Disease Foundation, Inc. (and other diseases of bone resorption) 200 Varick St., Suite 1004 New York, NY 10014-4810 (212) 229-1582 (800) 23-PAGET References JUVENILE OSTEOPETROSIS: EFFECTS ON BLOOD AND BONE OF PREDNISONE AND A LOW CALCIUM, HIGH PHOSPHATE DIET: L.M. Dorantes, et. al.; Arch Dis Child (July 1986, issue 61(7)). Pp. 666-670. BONE MARROW TRANSPLANTATION: RESEARCH REPORT; U.S. Dept. of Health and Human Services, National Cancer Institute. (September 1986, NIH publication No. 86-1178).