Pancytopenia, Fanconi

A genetic (inherited) disease that adversely affects all of the bone marrow elements and is closely associated with malformations of the heart, kidney and limbs (arms and legs) as well as pigmentary changes of the skin. Fanconi pancytopenia, often called Fanconi anemia, predisposes to cancer, particularly to a disturbance of bone marrow growth called myelodysplasia and to acute myeloid leukemia. Patients tend also to develop cancers in areas of the body where cells normally reproduce rapidly, such as the mouth, esophagus, the intestinal and urinary tracts, and the reproductive organs. Children with Fanconi anemia usually have low birth weight, are smaller than average and often have birth defects such as: {{}}Café-au-lait (coffee with milk) spots in the skin. Brownish pigmentation of the body so it has a suntanned look. Small head (microcephaly). Small eyes (microphthalmia) and other eye anomalies. Thumb and forearm anomalies (quite typical) with: {{}}Misshapen or missing thumbs; and Underdeveloped or missing radius (a forearm bone). Kidney and ureter malformations. Small penis and small testes. Mental retardation (in a quarter of cases) and learning disabilities. A test for Fanconi anemia involves chromosome breakage. White blood or other cells are treated in the laboratory with a chemical, diepoxybutane (DEB) or mitomycin C (MMC), that crosslinks the strands of DNA. Normal cells correct most of the damage produced by DEB or MMC. Fanconi anemia cells cannot repair the damage and show marked chromosome breakage. DNA tests can also identify specific mutations in Fanconi families and can be performed on a single cell. Fanconi anemia is a recessive condition. Both parents carry the same mutation (gene change). Each of their children has a 1 in 4 chance of inheriting the mutant gene from both parents resulting in the disease. At least 8 different mutations are capable of causing the disease. All these mutations appear to be at the same location in chromosome band 16q24.3. The short-term treatment of Fanconi anemia includes blood transfusions for the anemia and antibiotics for infections. Long-term treatment includes giving androgens (male hormones) and hematopoietic (blood-stimulating) growth factors. Androgens stimulate the production of red blood cells, often platelets and sometimes white cells; this treatment may be effective for years, but most patients eventually fail to respond. Growth factors such as G-CSF may boost the production of white cells. Bone marrow transplantation is currently the only long-term cure for the bone marrow disease in Fanconi anemia. Gene therapy trials are in progress. The disorder is named for a Swiss pediatrician, Guido Fanconi, who first reported it in 1927.