A 6-year-old boy is brought to the office by his mother due to bleeding gums for the past 3 months. The patient brushes his teeth regularly and visits a dentist twice per year; his most recent dentist appointment 6 months ago was normal. The patient has become easily fatigued over the last 3-4 weeks and is not as active as he was previously. Height is below the 5th percentile and weight is at the 25th percentile for age. Several small patches of hypopigmentation are noted on the trunk. The thumbs appear hypoplastic and thenar eminences are flattened. Laboratory results are as follows:
| Leukocytes | 3,000/mm3 |
| Hemoglobin | 6.5 g/dL |
| Mean corpuscular volume | 112 µm3 |
| Platelets | 40,000/mm3 |
Which of the following is the most likely cause of this patient's condition?
Fanconi anemia | |
Pathophysiology |
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Clinical findings |
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Laboratory findings |
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Treatment |
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This patient most likely has Fanconi anemia (FA), the most common congenital cause of aplastic anemia (ie, bone marrow failure, pancytopenia). FA is typically an autosomal recessive disorder caused by a DNA repair defect. Damaged, unstable DNA impairs normal hematopoietic stem cell production and can also lead to increased susceptibility to malignancy (eg, leukemia).
Patients usually present in childhood with signs of thrombocytopenia (eg, bleeding, bruising), as in this case, with progression to leukopenia (eg, infections) and anemia (eg, fatigue) over time. Anemia is usually macrocytic due to fetal erythropoiesis that occurs during periods of chronic hematopoietic stress. Additional characteristic features of FA include short stature, hyper- or hypopigmentation, and absent or hypoplastic thumbs, as seen in this patient. Additional abnormalities of the hand may include polydactyly or a flat thenar eminence.
Diagnosis of FA is made by demonstrating chromosomal breakage following DNA exposure to interstrand crosslinking agents. Definitive treatment is hematopoietic stem cell transplantation.
(Choice A) Benzene, found in solvents, polishes, and gasoline, is an industrial chemical that can cause chromosomal breakage and aplastic anemia. However, this patient's thumb and skin findings are suggestive of FA.
(Choice B) Cobalamin (vitamin B12) deficiency presents with macrocytic anemia and is most commonly caused by pernicious anemia or inadequate dietary intake, which are both extremely rare in children.
(Choice C) Congenital infections (eg, toxoplasmosis, rubella, cytomegalovirus) may cause dysmorphisms and perinatal morbidity (eg, growth restriction) and mortality but not chronic pancytopenia.
(Choice E) Glucose-6-phosphate dehydrogenase deficiency is a red blood cell enzyme deficiency causing anemia. Oxidant stress (eg, sulfonamides, fava beans, infection) in affected patients can cause episodic hemolysis but not leukopenia or thrombocytopenia.
(Choice F) A minority of patients with thymic tumors (eg, thymoma) have red cell aplasia, but lymphocyte and platelet counts are normal. Thymic tumors are rare in children.
Educational objective:
Fanconi anemia is the most common cause of congenital bone marrow failure and is due to defective DNA repair. In addition to pancytopenia, characteristic features include short stature, thumb anomalies, and abnormal skin pigmentation.