Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rickets is a common and paradoxical feature of infantile malignant osteopetrosis and results from the inability of osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. Despite a markedly positive total body calcium balance, rickets arises when the serum calcium x phosphorus product is insufficient to mineralize newly formed chondroid and osteoid. In five children with malignant infantile osteopetrosis, there were clinical, radiographic, biochemical, and histologic findings of rickets. Characteristic biochemical abnormalities included hypocalcemia, hypophosphatemia, and elevated levels of serum acid phosphatase, alkaline phosphatase, c-terminal parathyroid hormone, and 1,25-dihydroxyvitamin D. The urinary calcium/creatinine ratio was markedly depressed. The serum calcium x phosphorus product was below 30 in all children at the time the rickets was diagnosed, and above 40 by the time the rickets had resolved. Baseline bone density measurements were markedly elevated in all children (> 5 standard deviation above normal) and showed even significant increases (> 7 SD) when the rickets was treated with vitamin D and calcium. The children showed marked clinical improvement, decreased lethargy, increase in mobility and activity, and stimulation of appetite, without any additional adverse hematologic or neurologic effects. The rickets was reversible in all children: in one by HLA-identical sibling bone marrow transplantation and in four by physiologic doses of vitamin D and calcium. The parathyroid and renal responses to hypocalcemia were appropriate, but glucocorticoids, used in treating the hematologic complications of the disease, may have blunted the intestinal response to maximal vitamin D stimulation. This latter blockade can be overcome by increasing dietary calcium. By liberalizing rather than by restricting calcium and phosphorus intake, hypocalcemia can be minimized, phosphorus metabolism can be improved, and rickets can be cured.
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PMID:Osteopetrorickets. The paradox of plenty. Pathophysiology and treatment. 839 71

A newborn girl with hemorrhagic purpura, suspected neonatal sepsis, and pale and dry skin was lethargic with remarkable hepatosplenomegaly, convergent strabismus, severe anemia, and elevated alkaline phosphatase activity. Radiographs showed a generalized increase in bone density, small medullary cavities, sclerosis of the skull and vertebrae, transverse wavy stripes of sclerotic bone in the metaphyses, and bone-in-bone appearance in phalanges of hands and feet. On this basis, she was diagnosed with malignant infantile osteopetrosis. On the first day of life, the infant was given a blood transfusion and vitamin K (1 mg intravenously [iv]). Corticosteroid therapy was started with prednisone (2 mg/kg per day). She showed marked improvement of symptoms. On the 26th day and 42nd day of life, she received additional blood transfusions. On the 49th day, the patient was discharged and corticosteroid therapy was continued at a regimen of 5 mg/day. Subsequent blood sample analyses revealed normal values for age. At 1 year of life, a bone marrow sample showed normal white and red cell lineages. X-ray confirmed attenuation of the bone sclerosis; therefore, bone marrow transplantation (BMT) was not implemented. At the age of 1.5 years, prednisone therapy was discontinued gradually and withdrawn before the age of 2 years. Subsequent follow-up showed normalization of all radiological and hematologic parameters. At present, the patient is 3 years old and appears healthy with apparently complete regression of the disease.
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PMID:Apparent cure of a newborn with malignant osteopetrosis using prednisone therapy. 1176 Aug 52