Review Question - QID 108232

Childhood gallstones are often the presenting sign of hereditary spherocytosis, a diagnosis that is supported by the indirect bilirubinemia, the normocytic anemia, and the negative Coombs test. Hereditary spherocytosis will show red blood cells without central pallor as seen in the illustration provided in this answer.

Hereditary spherocytosis is caused by a genetic deficiency in a number of RBC cytoskeletal elements such as spectrin, ankyrin, or Band 3.1. Mutations in these proteins cause affected RBCs to lack the normal biconcave shape and instead to round into spherocytes. The membranes of these cells are less stable than normal, therefore they are more easily destroyed during passage through the spleen. This increased consumption of RBCs leads to production of bilirubin thereby leading to an indirect hyperbilirubinemia; this further leads to gallstones when the bilirubin precipitates as calcium bilirubinate in the gallbladder.

Dhaliwal et al. claim that hereditary membranopathies including spherocytosis usually result from autosomal dominant mutations in the red blood cell membrane. This leads to increased breakdown in the spleen and thereby causes the signs of extravascular hemolysis. Importantly, they note that a direct antiglobulin test (Coombs test) needs to be performed in order to distinguish hereditary spherocytosis from immune mediated anemias that can also present with spherocytes on blood smear.

Christensen et al. claim that the disorder is the third most common hemolytic condition after G6PD deficiency and ABO hemolytic disease. It is also therefore the most common direct Coomb's negative hemolytic anemia and should be evaluated in all patients who present with either jaundice or anemia of unknown origin. They predict that as physicians become more familiar with this disorder the number of patients who will present with this disorder symptomatically later in life will decrease due to better early detection.

Illustration A shows spherocytes - red blood cells that do not exhibit central pallor when seen on blood smear. Note that the majority of RBCs are spherocytes and that there are no other categories of abnormal blood cells in this disorder.

Incorrect Answers:
Answer 1: Hypersegmented neutrophils are present in megaloblastic anemias such as folate or B12 deficiency.
Answer 2: Schistocytes can be seen either due to mechanical trauma or microangiopathic anemias, neither of which present with the symptoms seen here.
Answer 3: Sideroblasts are characteristic of sideroblastic anemias such as lead poisoning..
Answer 5: Dacrocytes are present in myelofibrosis, which presents much later in life.