A 4-year-old boy is brought to the office by his mother due to bruising. Over the last month, he has developed multiple bruises along his chest, back, and legs. The patient normally is very active and enjoys playing outside with his older siblings; however, he has been more tired than usual and takes longer naps. He has also had a poor appetite. For the past week, the patient's gums have been oozing blood during tooth brushing. He takes no daily medications. Last year, the patient had a tonsillectomy with no complications. His paternal uncle has hemophilia. Vital signs are normal. The patient appears pale and tired. Examination shows a few hematomas on the buccal mucosa. Scattered bruises and petechiae are present on the shins, anterior chest, and back. Nontender anterior cervical lymphadenopathy is palpated bilaterally. Abdominal examination shows hepatosplenomegaly. No joint swelling is present. Further evaluation of this patient would most likely reveal a deficiency in which of the following?
Acute lymphoblastic leukemia | |
Epidemiology |
|
Clinical |
|
Evaluation |
|
*≥2 cytopenias (leukocytes may be ↓ or ↑), ± blasts on peripheral smear. | |
This patient's bruising, nontender lymphadenopathy, and hepatosplenomegaly are concerning for acute lymphoblastic leukemia (ALL). ALL is the most common childhood cancer, with peak incidence in boys age 2-5.
Pathogenesis of ALL involves rampant growth and overcrowding of leukemic cells in the bone marrow. This halts the production of normal cell lines, and about half of patients with ALL present with bruising, petechiae, and mucosal bleeding (eg, oozing from the gums) due to impaired platelet production. Bone marrow failure also leads to pallor and fatigue (from anemia) and recurrent infections (from neutropenia). Nonspecific symptoms (eg, poor appetite) are common.
The spread of leukemic cells out of the bone marrow can cause the liver, spleen, and lymph nodes to enlarge. In contrast to infectious causes of lymphadenopathy, malignant nodes are typically firm and nontender, as seen in this child. Bone marrow biopsy is diagnostic.
(Choice A) Connective tissue disorders (eg, Ehlers-Danlos syndrome) and vitamin C deficiency (scurvy) may present with fragile, easily bruised skin due to impaired collagen synthesis; however, lymphadenopathy and hepatosplenomegaly would not be expected with either condition. Scurvy is also exceedingly rare and unlikely to develop from a month of poor appetite.
(Choice B) Hemophilia A (factor VIII deficiency) typically presents with prolonged bleeding after minor trauma (eg, hemarthrosis). This inherited bleeding disorder would be unlikely in a child without complications after a surgical procedure and with new onset of symptoms, as in this case. Moreover, although this patient has a family history of hemophilia, the disease is X-linked recessive and inherited in boys from maternal chromosomes (not the paternal uncle).
(Choice D) Factor VII requires vitamin K–dependent gamma-carboxylation to be active in the clotting pathway. In children, vitamin K deficiency is typically seen in chronic disorders of fat malabsorption (eg, cystic fibrosis) and is unlikely in this previously healthy child with no gastrointestinal symptoms.
(Choice E) Von Willebrand factor (VWF) is a protein that allows platelet adhesion. Decreased VWF production, as seen in von Willebrand disease, typically presents with minor bruising and bleeding despite a normal platelet count. This condition would not explain this patient's lymphadenopathy and hepatosplenomegaly.
Educational objective:
Acute lymphoblastic leukemia often presents with bruising, petechiae, and bleeding due to impaired platelet production in the bone marrow. Other common findings are nontender lymphadenopathy and hepatosplenomegaly.