A 5-year-old boy is brought to an urgent care center due to fatigue. His mother says, "Normally, my son is running and jumping, but for the past week he has been resting on the couch and sleeping more than usual. His eyes also look a bit yellow." He has had no fevers, vomiting, or difficulty breathing. A week ago, the patient had a skin infection that resolved after treatment with oral antibiotics. Review of medical records shows a normal hemoglobin screening at his 1-year well-child visit. Family history is significant for a maternal uncle who had several similar episodes of tiredness and jaundice. Physical examination reveals a tired-appearing boy lying on the examination table watching television. His neck is supple without lymphadenopathy, and scleral icterus and mild jaundice are present. His cardiac and abdominal examinations are normal. Laboratory results are as follows: Peripheral blood smear is notable for red blood cell fragments and intracellular deposits of denatured hemoglobin. Which of the following is the next best step in the diagnostic workup for this patient?

Question

A 5-year-old boy is brought to an urgent care center due to fatigue.  His mother says, "Normally, my son is running and jumping, but for the past week he has been resting on the couch and sleeping more than usual.  His eyes also look a bit yellow."  He has had no fevers, vomiting, or difficulty breathing.  A week ago, the patient had a skin infection that resolved after treatment with oral antibiotics.  Review of medical records shows a normal hemoglobin screening at his 1-year well-child visit.  Family history is significant for a maternal uncle who had several similar episodes of tiredness and jaundice.  Physical examination reveals a tired-appearing boy lying on the examination table watching television.  His neck is supple without lymphadenopathy, and scleral icterus and mild jaundice are present.  His cardiac and abdominal examinations are normal.  Laboratory results are as follows:  Peripheral blood smear is notable for red blood cell fragments and intracellular deposits of denatured hemoglobin.  Which of the following is the next best step in the diagnostic workup for this patient?

Quizplus · Accepted Answer

Explanation: 11ec2b69_c164_7823_8f63_b19ba7ee7eec_MD0005_00 Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder most common in patients of Asian, African, or Middle Eastern descent. G6PD normally protects the red blood cells (RBCs) from oxidative stress by producing NADPH, an important cofactor in the pathway of oxidant inactivation. Deficiency of G6PD leads to intra- and extravascular hemolysis triggered by oxidative stress, such as infection, sulfa drugs, or fava beans. In this patient, the recent oral antibiotic was most likely trimethoprim-sulfamethoxazole, a sulfa drug. Clinical manifestations include jaundice and fatigue. Laboratory evidence of hemolysis includes anemia (normocytic, normochromic), indirect hyperbilirubinemia, low haptoglobin, and elevated lactate dehydrogenase. Peripheral smear shows characteristic bite cells and schistocytes (RBC fragments); Heinz bodies (accumulations of denatured hemoglobin) may be seen with special staining. bite cells A low G6PD assay, which detects NADPH formation, is diagnostic. This assay can be falsely negative if measured while the most severely G6PD-deficient RBCs are already hemolyzed; therefore, if the initial result is negative but there is strong suspicion for G6PD, the assay should be repeated after the acute episode. The acute hemolytic anemia typically self-resolves in 1-2 weeks after removal of the offending oxidant. Patients should be counseled on how to avoid common triggers. (Choice A) Bone marrow biopsy is indicated for suspicion of bone marrow suppression or failure, which typically presents with multiple cytopenias (eg, thrombocytopenia, leukopenia) and a low reticulocyte count. In contrast, this patient has isolated anemia and a compensatory reticulocytosis. (Choice B) Cold agglutinin titer is elevated in cold agglutinin-mediated autoimmune hemolytic anemia, which can also present with fatigue and anemia. However, symptoms typically develop after a viral infection, and a direct antiglobulin test would be positive. (Choice D) Hemoglobin electrophoresis detects hemoglobinopathies such as thalassemia and sickle cell disease. Anemia in thalassemia is microcytic, and patients with sickle cell anemia typically have pain crises starting in infancy and sickled RBCs on peripheral smear. This patient has a normocytic anemia with a characteristic peripheral smear of G6PD deficiency. (Choice E) Osmotic fragility testing is abnormal in hereditary spherocytosis, a genetic hemolytic anemia with spherocytes on peripheral smear and splenomegaly on examination, neither of which is seen in this patient. Educational objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder in which acute hemolytic anemia is triggered by oxidative stress (eg, sulfa drug). Presentation includes jaundice and fatigue, and a G6PD assay is diagnostic. References: Congenital hemolytic anemia. (http://www.ncbi.nlm.nih.gov/pubmed/28189176)

A 5-Year-Old Boy Is Brought to an Urgent Care Center