Constitutive elevation of serum alpha-fetoprotein in Fanconi anemia

The diagnosis of Fanconi anemia (FA) is based on the association of congeni tal malformations, bone marrow failure syndrome, and hypersensitivity to ch romo somal breaks induced by cross-linking agents. In the absence of typica l features, the diagnosis is not easy to establish because there is no simp le and cost-effective test; thus, investigators must rely on specialized an alyses of chromosomal breaks. Because we observed elevated serum alpha-feto protein (sAFP) levels in FA patients, we investigated this parameter as a p ossible diagnostic tool. Serum AFP levels from 61 FA patients and 27 contro ls with acquired aplastic anemia or other inherited bone marrow failure syn dromes were analyzed using a fluoroimmunoassay based on the TRACE technolog y Serum AFP levels were significantly more elevated (P < .0001) in FA than in non FA aplastic patients. In the detection of FA patients among patients with bone marrow failure syndromes, this assay had a sensitivity of 93% an d a specificity of 100%, This elevation was not explained by liver abnormal ities. Levels of sAFP were unchanged during at least 4 years of follow-up, and allogeneic bone marrow transplantation did not modify sAFP levels. Thre e of 4 FA patients with mosaicism as well as 5 of 6 FA patients with myelod ysplastic syndrome were detected by this test. Heterozygous parents of FA p atients had normal sAFP levels. Measurement of sAFP levels with this automa ted, cost effective, and reproducible fluoroimmunoassay could be proposed f or the preliminary diagnosis of FA whenever this disorder is suspected. (C) 2000 by The American Society of Hematology.