Constitutive elevation of serum alpha-fetoprotein in Fanconi anemia.
The diagnosis of Fanconi anemia (FA) is based on the association of congenital malformations, bone marrow failure syndrome, and hypersensitivity to chromosomal breaks induced by cross-linking agents. In the absence of typical features, the diagnosis is not easy to establish because there is no simple and cost-effective test; thus, investigators must rely on specialized analyses of chromosomal breaks. Because we observed elevated serum alpha-fetoprotein (sAFP) levels in FA patients, we investigated this parameter as a possible diagnostic tool. Serum AFP levels from 61 FA patients and 27 controls with acquired aplastic anemia or other inherited bone marrow failure syndromes were analyzed using a fluoroimmunoassay based on the TRACE technology. 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% and a specificity of 100%. This elevation was not explained by liver abnormalities. Levels of sAFP were unchanged during at least 4 years of follow-up, and allogeneic bone marrow transplantation did not modify sAFP levels. Three of 4 FA patients with mosaicism as well as 5 of 6 FA patients with myelodysplastic syndrome were detected by this test. Heterozygous parents of FA patients had normal sAFP levels. Measurement of sAFP levels with this automated, cost-effective, and reproducible fluoroimmunoassay could be proposed for the preliminary diagnosis of FA whenever this disorder is suspected.
Nuclear Medicine Department, the Department of Bio-Statistics, and the Hematology Bone Marrow Transplantation Department, Saint-Louis Hospital, Paris, France.
B
B
Cassinat
P
P
Guardiola
S
S
Chevret
M H
MH
Schlageter
M E
ME
Toubert
J D
JD
Rain
E
E
Gluckman
D000293:Adolescent; D000328:Adult; D001681:Biological Assay; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D000509:alpha-Fetoproteins / Q000032:analysis*
D015415:Biomarkers; D000509:alpha-Fetoproteins