Hereditary spherocytosis

Abstract

Hereditary spherocytosis is a common inherited disorder that is characterised by anaemia, jaundice, and splenomegaly. It is reported worldwide and is the most common inherited anaemia in individuals of northern European ancestry. Clinical severity is variable with most patients having a well-compensated haemolytic anaemia. Some individuals are asymptomatic, whereas others have severe haemolytic anaemia requiring erythrocyte transfusion. The primary lesion in hereditary spherocytosis is loss of membrane surface area, leading to reduced deformability due to defects in the membrane proteins ankyrin, band 3, beta spectrin, alpha spectrin, or protein 4.2. Many isolated mutations have been identified in the genes encoding these membrane proteins; common hereditary spherocytosis-associated mutations have not been identified. Abnormal spherocytes are trapped and destroyed in the spleen and this is the main cause of haemolysis in this disorder. Common complications are cholelithiasis, haemolytic episodes, and aplastic crises. Splenectomy is curative but should be undertaken only after careful assessment of the risks and benefits.

Additional erythrocytic and reticulocytic parameters helpful for diagnosis of hereditary spherocytosis: results of a multicentre study

“…Hereditary Spherocytosis (HS) [1][2][3] is the most common cause of inherited chronic haemolysis in northern Europe and North America where it affects one person in 2000. HS refers to a group of heterogeneous regenerative haemolytic anaemias characterised by a loss of membrane surface area, leading to reduced deformability due to defects in proteins in the erythrocytic membrane (ankyrin, band 3 protein, β-spectrin, α-spectrin, or protein 4.2).…”

“…However, all tests suffer from specific limitations. Osmotic fragility test lacks of sensitivity and specificity [3].…”

“…Moreover, in mild or atypical cases, difficult interpretation is likely to occur. SDS-PAGE lacks sensitivity to very mild or asymptomatic HS carriers [2], and a high reticulocyte count might mask a reduction in ankyrin-1 in SDS-PAGE [4] whereas an ankyrin-1 defect represents 40-65% of HS in the USA and Europe [3]. A key test for HS, osmotic gradient ektacytometry, is only available in specialised laboratories.…”

“…Polyspecific DAT reagents may also fail to detect some autoantibodies, particularly IgA autoantibodies. Moreover, diagnosis is often more difficult during the neonatal period than later in life, for many reasons [2,3].…”

“…In conclusion, the development of simple, fast, accurate, sensitive, and specific diagnostic laboratory tests for hereditary spherocytosis is a real challenge [2,3]. Some authors recommend automated red cell indices to predict or identify HS.…”