Fanconi anemia in infancy: report of hematopoietic stem cell transplantation to a 13-month-old patient

Abstract

The most important clinical features of Fanconi anemia (FA) are hematologic disorders and these are responsible for high incidence of morbidity and mortality. During birth, the blood count is usually normal and macrocytosis is often the first detected abnormality. This is typically followed by thrombocytopenia and anemia; then, progresses to pancytopenia. The majority of patients develop progressive bone marrow failure or acute myelogenous leukemia, both of which are diagnosed with peak frequencies at the age of 7 and 10–15 years, respectively [1, 2]. The disease has generally been managed by the administration of blood products, treatment of infections, and prolonged administration of androgens and hematopoietic growth factors. However, the only curative treatment for the bone marrow failure is hematopoietic stem cell transplantation (HSCT). We describe a patient demonstrating pancytopenia from birth, who received HSCT at the age of 13 months. The patient showed a tendency toward intrauterine growth retardation on ultrasonographic examination at 29 weeks of gestation. He was delivered by cesarean section at 36 weeks and 6 days of gestation because of fetal distress. Birth weight was 2070 g, and 1and 5-min Apgar score were 6 and 8, respectively. He was referred to the neonatal intensive care unit in our hospital for respiratory distress and cardiac murmur on the day of birth. On admission, white blood cell count was 2.8 9 10/L, hemoglobin 5.1 g/dL, platelet count 95 9 10/L. Congenital abnormalities suggestive of FA were bilateral radial hypoplasia, bilateral defective thumbs, defect of the left kidney and L-form fused kidney on the right side, and small patent ductus arteriosus. Bone marrow showed a hypo cellular picture, being comprised mainly of lymphocytes. Karyotyping of 20 cells that were in metaphase exclusively showed 46, XY. A diagnosis of FA was established at the age of 3 months based on the increased chromosomal breakage induced by mitomycin C. The rate of chromosomal breakage in him was increased (443/ 100 cells) compared with control cells (18/100 cells). Levels of FANCA and monoubiquitinated and non-ubiquitinated forms of FANCD2 were determined using immunoblotting analyses of whole cell extracts with antiFANCA and anti-FANCD2 antibodies, and he lacked FANCA protein expression and FANCD2 monoubiquitination. For about a year before transplant, he became progressively dependent on red blood cell and platelet concentrate transfusion and the absolute neutrophil count was 0.05–0.65 9 10/L. He was not treated with any growth factors or androgens. He developed severe sepsis twice at the ages of 9 and 12 months, respectively. Bone marrow at the age of 12 months was hypo cellular with dysplastic features suggesting myelodysplastic syndrome (MDS) and the percentage of myeloblasts was \5%. That indicated refractory cytopenias with multilineage dysplasia. Karyotyping of 20 cells exclusively showed 46, XY with abnormality of add(2)(q33). Before transplant, he had been transfused with red blood cells 18 times and platelet K. Oshima (&) A. Kikuchi S. Mochizuki D. Toyama N. Uchisaka R. Hanada Division of Hematology/Oncology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki-ku, Saitama 339-8551, Japan e-mail: oshima-k@umin.ac.jp