Fanconi Anemia

Inherited anemia leading to bone marrow failure, myelogenous leukemia, and, in older patients, many cancers (head and neck, esophageal, gastrointestinal, vulvar, anal).

Type I Fanconi Pancytopenia.

Genetically inherited anemia. Named after the Swiss pediatrician, Guido Fanconi.

Rare, with carrier frequency of 1:300 in the general population (1:89 in the Ashkenazi Jewish population). Occurs equally in males and females and is found in all ethnic groups. The International Fanconi Anemia Registry (Rockefeller University, New York, NY) maintains case data on more than 3000 patients.

Fanconi anemia (FA) comprises a group of monogenic autosomal recessive disorders resulting from mutations in one of eight Fanconi anemia genes (A, B, C, D1, D2, E, F, G). Although caused by rather simple mutations, the disorder shows a complex phenotype with many features, including developmental abnormalities, severe anemia, and/or eventually leukemia and various cancers. Many patients die during their mid-teen years. Mutations in FA-A and FA-C account for 76% of patients worldwide.

Spontaneous chromosomal aberrations associated with hypocellular marrow, pancytopenia, and constitutional aplastic anemia.

Usually diagnosed by age 6 years, after onset of hematologic abnormalities. It may be diagnosed as early as the neonatal period while investigated for other associated anomalies. Diepoxybutane, a DNA cross-linking agent, is a unique marker for Fanconi anemia cells. Currently, the definitive diagnostic test is a chromosome breakage test with a chemical, either diepoxybutane or mitomycin C, that cross-links DNA. Normal cells are able to correct most of the damage caused by these agents, whereas Fanconi anemia cells show marked chromosome breakage. These tests can be performed prenatally on cells from chorionic villi or from the amniotic fluid.

Pancytopenia, with mean survival of 5 years after diagnosis, low birth weight, skeletal anomalies (hips, spine, ribs), short stature, microcephaly, microphthalmia, microstomia, radial ray/thumb abnormalities, polydactyly, syndactyly, misplaced radial artery, renal abnormalities, cardiac defects, and developmental delay.

Check a complete blood cell count (CBC) for anemia and thrombocytopenia. Check electrolytes in presence of renal defects. Complete physical evaluation must be obtained to eliminate the presence of cardiac defects.

Maintain oxygen carrying capacity with red blood cell transfusion. Anticipate need for platelet transfusion. Avoid central neuraxial anesthesia techniques in presence of coagulopathy. Direct laryngoscopy and tracheal intubation can be difficult in the presence of macrostomia.

Prophylactic antibiotic must be considered in case of cardiac defect.

Bloom Syndrome: Autosomal recessive inherited disorder characterized by prenatal and postnatal growth retardation, photosensitivity, telangiectasias, skin pigment anomalies, and increased risk of malignancies most likely caused by chromosomal instability. Most interchanges occur between homologous chromosomes, not between nonhomologous chromosomes as in Fanconi anemia.

Blackfan-Diamond Syndrome: Congenital hypoplastic anemia manifesting in the first year of life, with increased risk for leukemia. High adenosine deaminase activity in the blood.

TAR Syndrome: Rare condition associated with thrombocytopenia and bilateral radial aplasia first described in 1951. The frequency is 0.42:100,000 live births in Spain. Autosomal recessive inheritance, also presenting abnormalities in skeletal, gastrointestinal, hematologic, and cardiac systems. Pancytopenia similar to Fanconi anemia. The major cause of mortality is hemorrhage. The incidence of hemorrhage is limited to the first 14 months of life. Male and females are affected equally.

Congenital Dyserythropoietic Anemias: Group of inherited disorders characterized by quantitatively and qualitatively altered erythropoiesis resulting in usually mild-to-moderate anemia. Premature destruction of erythroblasts in the bone marrow reduces the number of them reaching maturity. In addition, there is also peripheral destruction of these dysplastic erythroblasts.

Hexokinase-Deficiency Hemolytic Anemia, Chronic: Autosomal recessive pattern characterized by chronic hemolytic anemia associated with severe deficiency of red cell glucose phosphate isomerase. Some cases of autosomal dominant transmission have been reported. Like the phosphofructokinase and pyruvate kinase, the hexokinase enzyme is a rate-limiting factor in the metabolism of glucose in the Embden-Meyerhof pathway. Because glycolysis is the only source of energy for the red cells, deficiency in hexokinase results in chronic hemolytic anemia. A few allelic variants have been described for this chronic form: Fukuoka: Reported in the Japanese literature as the association of chronic glucose phosphate deficiency and a history of prolonged neonatal jaundice. Iwate: Chronic form of hemolytic anemia most often homozygous in pattern and detected early in life. Homburg: Association of chronic hemolytic anemia and neurologic deficits. Anesthetic considerations must include a proper evaluation of the hematocrit and the possibility of intraoperative transfusion. Administration of glucose solution can exaggerate the hemolytic reactions.