Osteopetrosis Support Trust

TYPES OF OSTEOPETROSIS The disease occurs in a variety of forms, listed here in approximate order of severity beginning with the mildest: Transient Infantile Osteopetrosis This is the least reported form of the disease and resolves without intervention. It may represent a mild form of the disease showing early in the life of a carrier, although this has not been proven. The importance of knowing of this disease subtype is that it highlights the need to perform a check X-ray in any child about to undergo bone marrow transplantation just before chemotherapy commences. This will reduce the risk (albeit very small) of transplanting a child with self-resolving osteopetrosis. Adult, "benign", Autosomal Dominant Osteopetrosis This was the first form of the disease to be described, by a German radiologist called Albers-Schönberg, and occurs in two forms: * Type I which is typified by thickening (sclerosis) of the dome of the skull (skull vault) * Type II (classical Albers-Schönberg disease) where the spine has a so-called "rugger jersey" striped appearance and the pelvic bones contain endobones. This is the commonest form of the disease and is usually diagnosed in adolescence or early adulthood. Different estimates suggest that between 1 in every 20,000-500,000 people are affected. Inheritance is autosomal dominant although the disease may vary in severity between generations of the family. The most common symptoms are an increased risk of fracture, back / bone pain, headache and osteomyelitis (infection of the bone). Problems due to nerve compression (deafness, visual loss and facial nerve paralysis) occur much more rarely than in the severe infant forms. The gene responsible for most cases of type II disease has been pinpointed to the ClCN7 chloride channel gene. Carbonic 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). As well as causing increased bone density and a tendency to fracture easily there are characteristic changes in body chemistry. 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 (termed renal tubular acidosis). CAII must also have an important role in the brain and affected children therefore develop progressive cerebral calcification and mental retardation. Growth failure and dental malocclusion are other problems. This 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. Approximately three fifths of children develop nerve compression where nerves pass through the skull: this most commonly causes blindness, but can also result in hearing loss and facial palsy. Unlike malignant infantile osteopetrosis described below blood problems tend to be minor or absent. Treatment with oral bicarbonate supplements does not seem to change the course of the disease. Bone marrow transplantation normalises bone density by providing healthy osteoclasts, but does not seem to prevent cerebral calcification and mental decline. This disease should be excluded in every child with osteopetrosis, at the very least by scrutiny of blood bicarbonate and chloride and urine pH, but preferably by measuring CAII activity. This is particularly important in children of Mediterranean or Arab race and in children lacking blood derangement. Malignant Infantile Osteopetrosis This is the commonest of the severe forms of infantile osteopetrosis and is caused by faults in at least four different genes. Most children develop severe nerve damage early in life and two thirds of affected children die by the age of 6 years without treatment. Currently the only curative treatment is bone marrow transplantation. This can completely prevent further progression of the disease in most children, although in a small percentage of cases the bones do not respond. The commonest symptoms in order of frequency are: <ul type="disc" style="margin-top: 0cm;"><li class="MsoNormal">Snuffles Nasal congestion and discharge start very early in life and are generally constant. This is caused by overgrowth of the upper nasal bones and not, as some think, by persistent viral infections. </li><li class="MsoNormal">Impaired vision This is the commonest symptom leading to medical diagnosis and is typically apparent by the second to fourth month of life. Approximately 75% of children with malignant infantile osteopetrosis will develop visual impairment, almost always within the first year of life. In many children optic nerve damage becomes apparent at around 6-8 weeks when they would usually begin to fix and follow faces, lights and large objects. Due to lack of proper fixation the eyes begin to scan rapidly from side to side. These wobbly movements are called nystagmus. The optic nerve carries impulses from the retina at the back of the eye to the brain and passes through a bony optic canal in the skull on its way from the eye socket to the brain. If formation of new bone by osteoblasts in this area is not opposed by osteoclasts the canal progressively narrows, putting pressure on the blood vessels which surround the nerve and feed it. This can be seen on computerised tomography (CT) scans as shown below. In the cross-sectional scan the eyeballs can faintly be seen at the top. The optic nerve travels back from the middle of the eye ball passing through a passage in the bone - the optic canal. This is narrowed on the right hand side of this scan.</li></ul>