A 6-year-old boy is brought to the office due to fatigue and abdominal distension. The parents state that the patient bruises easily and appears pale. Physical examination shows subconjunctival pallor and several ecchymoses on the boy's extremities. His abdomen is distended with nontender massive splenomegaly and moderate hepatomegaly. Laboratory studies reveal that his hemoglobin level is 8 g/dL, leukocyte count is 3,800 cells/mm³, and platelet count is 90,000 cells/mm³. Bone marrow aspirate results are shown in the exhibit. Which of the following is the most likely diagnosis?

Question

Quizplus · Accepted Answer

Gaucher disease is an autosomal recessive lysosomal storage disease caused by a deficiency of beta-glucocerebrosidase. This enzyme is normally found in lysosomes where it functions to break down glucocerebroside (a glycolipid component of cell membranes). Deficiency leads to accumulation of glucocerebroside within the lysosomes of macrophages as they engulf and digest cellular debris; the resulting lipid-laden macrophages (Gaucher cells) have a characteristic "wrinkled tissue paper" appearance and can be found in the bone marrow and other affected tissues (eg, spleen). Clinical manifestations develop as abnormal Gaucher cells accumulate within body tissues and secrete lysosomal proteases and cytokines that disrupt cellular function. The onset of symptoms varies from childhood to early adulthood and includes the following: (Choice A) Acute lymphoblastic leukemia is one of the most common childhood cancers. Although leukemia can present with pancytopenia and hepatosplenomegaly, bone marrow or peripheral blood smear would reveal lymphoblasts. (Choice B) Epstein-Barr virus infection can present with fever, pharyngitis, cervical lymphadenopathy, fatigue, and splenomegaly. Atypical reactive lymphocytes would likely be found on peripheral blood smear, and Gaucher cells would not be expected in the bone marrow aspirate. (Choice C) Fanconi anemia is an inherited cause of aplastic anemia. In addition to pancytopenia, patients often have hypo/hyperpigmented patches, short stature, and hypoplastic thumbs, as well as an increased risk of malignancy (eg, acute myeloid leukemia). (Choice E) Parvovirus B19, a common cause of erythema infectiosum, can trigger a transient aplastic crisis in those with an underlying hematologic abnormality (eg, sickle cell disease, hereditary spherocytosis). Bone marrow aspirate would reveal erythroid precursors with intranuclear viral inclusions. Educational objective: Gaucher disease is a lysosomal storage disorder caused by beta-glucocerebrosidase deficiency that presents with bone pain, hepatosplenomegaly, and cytopenias. Glucocerebroside accumulation leads to distended macrophages with a "wrinkled tissue paper" appearance (Gaucher cells) that can be found in affected tissues (eg, bone marrow). __________ References: Clinical manifestations and management of Gaucher disease. (http://www.ncbi.nlm.nih.gov/pubmed/26604942)

A 6-Year-Old Boy Is Brought to the Office Due to Fatigue