Disease Information

Rare Diseases: Osteopetrosis (malignant infantile form)

Alternate Names: MIOP

Definition

Malignant infantile osteopetrosis (MIOP) is a rare disease that results in a child having abnormal bones. This disease occurs because cells, called osteoclasts, do not function properly. In order to maintain healthy bones, a balance must be maintained between cells called osteoblasts, which make new bone, and osteoclasts, which break down and get rid of old bone. Children affected with osteopetrosis do not have this balance as they have functioning osteoblasts and non-functioning osteoclasts. Since the osteoclasts do not function; these children do not have healthy bones. On an x-ray these bones look strong because one sees thick, white bones, but in actuality, these bones are weak and fracture more easily that a normal individual’s healthy bones.

Children with malignant infantile osteopetrosis may have other problems as a consequence of their disease, including short stature, dental problems, hearing loss and blindness. The life-threatening complication of MIOP is bone marrow failure. Early cells for red cells, white cells and platelets are made in the bone marrow. In MIOP, the bone marrow forms fibrous tissue and becomes crowded as the osteoblasts continue to make new bone. Without functioning osteoclasts to maintain the balance with osteoblasts, the osteoblasts take up all the space for the bone marrow with new bone and prevent the bone marrow from making new cells. Thus, children with MIOP become anemic and thrombocytopenic, and are unable to fight infections effectively without medical intervention.

Children with malignant infantile osteopetrosis typically are diagnosed in early infancy. Some of the earliest symptoms may be a large head (macrocephaly), failure to thrive, low platelets, low hemoglobin, large liver or spleen from the body trying to make blood cells in these organs, or a seizure caused by a salt imbalance from low calcium. The infantile form of osteopetrosis is highly fatal without curative therapy. Seventy percent of children with malignant infantile osteopetrosis die by the age of 6 years, and almost 100 percent do not live to the age of 10 years.

Incidence

• Osteopetrosis is a extremely rare congenital disorder. One of 200,000 children is affected by MIOP. To put this in perspective, in the United States, approximately 20 children will be born with this disease each year. Within the last decade, St. Jude Children’s Research Hospital has treated at least nine patients with this rare disorder, most within the last five years.

Influencing Factors

• Osteopetrosis is predominantly inherited as an autosomal recessive disorder, meaning that the child must have two abnormal genes for MIOP. For a child to inherit an autosomal recessive disorder, such as osteopetrosis, each parent carries a gene that is abnormal for the disorder; thus, the parents are carriers for the disorder. When the child inherits both abnormal genes, the child will have the disorder, as in the case of MIOP.

Treatment Strategies

Pharmacological (drug) therapy such as interferon gamma-1b has been attempted in children with osteopetrosis. While various medications may prolong the child’s life, these therapies will not cure the child of MIOP.

The only potentially curative therapy for MIOP at this time is a successful hematopoietic stem cell / bone marrow transplant, using either bone marrow or peripheral blood stem cells from an allogeneic (someone else) donor. The optimal donor would be a suitable matched sibling. However, only approximately 20-30 percent of children with osteopetrosis will actually have this option available.

An alternative donor is a matched-unrelated donor (MUD) that is identified through the National Marrow Donor Program  (NMDP). However, obtaining a MUD could delay the transplant for three to four months, during which time the child’s medical condition could quickly deteriorate. Therefore another donor alternative must be explored.

Current Research

• An alternative option that is currently being researched at St. Jude is a hematopoietic stem cell transplant from a partially mismatched family donor, such as a parent, for children with MIOP. This type of transplant will allow children with osteopetrosis to proceed to a potentially life-saving transplant quickly as a parent is typically available.
  
• In the attempt to avoid transplant-related toxicity, such as graft-versus-host-disease, from using a mismatched donor, the donor’s peripheral blood stem cells are filtered through a device to pull out specific cells – T-lymphocytes – that could cause transplant-related complications.
  
• The goal of the current St. Jude study is to proceed to transplant quickly with a parental donor once a child has been diagnosed with MIOP and a matched sibling donor is not available. Researchers hope that by proceeding to transplant quickly and trying new and innovative transplant treatment plans for children affected by osteopetrosis that these children will avoid disease progression (i.e. deafness and blindness) and may have a chance at a cure.

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