Hematopoietic Stem Cell Transplantation for Osteopetrosis




Osteopetrosis is the generic name for a group of diseases caused by deficient formation or function of osteoclasts, inherited in either autosomal recessive or dominant fashion. Osteopetrosis varies in severity from a disease that may kill infants to an incidental radiological finding in adults. It is increasingly clear that prognosis is governed by which gene is affected, making detailed elucidation of the cause of the disease a critical component of optimal care, including the decision on whether hematopoietic stem cell transplantation is appropriate. This article reviews the characteristics and management of osteopetrosis.


Osteopetrosis (OP) is the generic name for a group of diseases caused by deficient formation or function of osteoclasts (OC), inherited in either autosomal recessive (AR) or dominant (AD) fashion. These vary in severity from a disease that may kill infants to an incidental radiological finding in adults. It is increasingly clear that prognosis is governed by which gene is affected, making detailed elucidation of the cause of the disease a critical component of optimal care, including the decision on whether hematopoietic stem cell transplantation (HSCT) is appropriate. HSCT in patients with OP is associated with disease-specific problems that require careful management, including the potential for life-threatening post-transplant hypercalcemia, a high prevalence of pulmonary arterial hypertension (PAH) and, in at least 1 subtype of disease, failure to reverse osteosclerosis despite successful donor cell engraftment.


Major clinical features of OP


Aberrant resorption and remodeling of bone caused by defective OC function have many potential clinical consequences. (1) Fractures: bones are under-tubulated so that they break easily. Common fracture sites are long bones of the arms and leg, posterior ribs, and the acromial processes. (2) Central nervous system (CNS) and eye problems: bony overgrowth, or lack of remodeling, results in compression of nerves or blood vessels that pass through bones, especially the optic nerve (resulting in partial or complete visual loss) and, more rarely, the auditory and facial nerves. Arteries or venous sinuses within the skull can also be constricted, as can the foramen magnum. Early fusion of bones may result in craniosynostosis. Some patients have primary neurometabolic (neuronopathic) forms of OP and may have abnormal retinal pigmentation and cerebral atrophy. (3) Cytopenia/pancytopenia: bony encroachment on medullary cavities results in extramedullary hemopoiesis with hepatosplenomegaly and the potential for hypersplenism. Anemia and thrombocytopenia result and blood films often show a markedly leukoerythroblastic picture, with a high white blood cell count and high numbers of circulating stem cells. (4) Growth: most children with OP fall below the tenth percentile on growth charts and some have severe dwarfism. (5) Hypocalcemia: defective OC function can disturb calcium homeostasis, which may manifest as symptomatic hypocalcemia in the first few months of life, despite high total body calcium reserves. (6) Respiratory compromise: the skull base, choanal bones, and jaw are often severely affected, which produces persistent snuffling, noisy breathing, and upper airway obstruction, and may predispose patients to PAH. Patients often suffer increased ear, nose, and throat infections and respiratory infections. (7) Dentition: tooth eruption is often delayed and tooth quality is poor; osteomyelitis of the jaw can occur. (8) Involvement of other organ systems: the genes involved may have roles in other organs. For example, a small proportion of children have a severe neurometabolic disease and abnormalities of lymphocytes and immunoglobulin production are now recognized in some variants.

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Oct 3, 2017 | Posted by in PEDIATRICS | Comments Off on Hematopoietic Stem Cell Transplantation for Osteopetrosis

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