Hereditary spherocytosis is a haemolytic anaemia resulting from red blood cell membrane protein anomalies. The prevalence of the disease is around 1 in 5,000 in the white population of Northern Europe. The clinical manifestations of the disease are often most severe during the first year of life, with around 65% of patients being diagnosed during the neonatal period. Jaundice is the first clinical manifestation in newborns, with severe anaemia developing the first few days after birth. Splenomegaly is a frequently observed feature. Age of onset and severity vary considerably. The majority (60 to 70%) of patients with hereditary spherocytosis have moderate anaemia, resulting from incomplete compensation of hyperhemolysis. In the absence of jaundice, splenomegaly or complications, the disease may remain undetected. In the majority of cases, transmission is autosomal dominant but in 25 to 35% of cases no haematological anomalies are detected in either of the parents. In these cases the disease is caused either by a de novo mutation or by recessive transmission of a mutation in the alpha-spectrin gene (in cases of recessive transmission, a particular defective allele of the alpha-spectrin gene is often detected). Identification of partial membrane protein deficiencies has led to the biochemical classification of hereditary spherocytosis and selection of several candidate genes: alpha-spectrin (SPTA1), beta-spectrin (SPTB), ankyrin (ANK1) and band 3 (EPB3). Numerous mutations affecting these genes have been characterised and been shown to lead to loss of some red blood cell membrane proteins. This deficit leads to a decrease in membrane surface (a characteristic feature of spherocytes), which worsens during passage through the venous sinus of the spleen and is accompanied by cellular dehydration. Diagnosis of hereditary spherocytosis remains problematic and depends on several supportive factors: presence of spherocytes on a blood smear, increase in autohaemolysis after incubation, increased osmotic fragility and preferential sequestration of the erythrocytes in the spleen. At present, the most reliable diagnostic method is to study red blood cell deformability in function of the osmolality of the medium by ektacytometry. In newborns, as for all types of haemolytic anaemia, the treatment for hereditary spherocytosis involves management of the jaundice (phototherapy and even exchange blood transfusion if needed) to prevent hyperbilirubinemic encephalopathy. The persistence of profound anaemia requires red blood cell transfusions. During the first year of life, erythropoietin therapy may limit the number of transfusions required. Hereditary spherocytosis is the only congenital haemolytic anaemia for which a splenectomy proves consistently beneficial. Splenectomy may be indicated from 7 to 8 years of age. The recently applied approach of subtotal splenectomy allows the immunological function of the spleen to be preserved.
Last update: March 2006