Isolated congenital asplenia (ICA)


The spleen is involved in the immune response to pneumococcal infections. Splenic phagocytes play an important role in removal of complement opsonised pneumococci from the blood, a process which is enhanced by the presence of specific antibody against the polysaccharide capsule of the organism. These immunological observations are supported by clinical experience in which deficiency of specific antibody or hyposplenism led to an increase in the risk of pneumococcal disease.

Isolated congenital asplenia (ICA) is a rare form of primary immunodeficiency, which is characterized by the absence of a spleen at birth in individuals with no other developmental defects. Most affected individuals die of severe bacterial infections in early childhood, others are prone to life-threatening bacterial infections. Isolated asplenia is distinct from asplenia associated with other complex visceral defects, notably heterotaxy syndromes such as Ivemark syndrome.


Patients with ICA are born without a spleen and display no other known developmental anomalies. Overwhelming bacterial infections occur more frequently in children in whom a splenectomy was performed, in children with a condition of autosplenectomy who have sickle cell disease, and in children who have the asplenia syndrome (Ivermark's syndrome: congenital absence of the spleen, cardiovascular anomalies, and other malformations). Seven patients experienced several episodes of invasive bacterial infections, all caused by Streptococcus pneumoniae.


Mahlaoui, N., et al. J. Pediat. 158: 142-148, 2011.


ICA caused by mutation in the NK2 homeobox 5 gene on chromosome 5q35 with an autosomal dominant inheritance in some kindreds. Recently research showed, the unbiased analysis of exomes revealed heterozygous mutations in RPSA in 18 patients from eight kindreds, corresponding to more than half the patients and over one third of the kindreds studied. The clinical penetrance in these kindreds is complete. Expression studies indicated that the mutations carried by the patients - a nonsense, a frameshift duplication and five different missense - cause autosomal dominant ICA by haploinsufficiency. RPSA encodes ribosomal protein SA, a component of the small subunit of the ribosome.


Bolze, A. et al. Science. doi:10.1126/science.1234864


It is already known that congenital isolated asplenia is a rare condition, which is heterogeneous in its presentation. It also appears to be heterogeneous in its inheritance as, although the majority of families reported show autosomal dominant inheritance, there are at least two families in the literature now which demonstrate autosomal recessive inheritance. As no human genes have been identified as being causative in isolated asplenia as yet, abdominal ultrasound and blood film for Howell–Jolly bodies are the important investigations to perform in the first-degree relatives of affected individuals to diagnose asplenia.


Gilbert B, et al. Eur J Pediatr. 2002 Jul;161(7):368-72.


It is difficult to recognize children with isolated congenital asplenia who are otherwise normal but who have increased susceptibility to overwhelming bacterial sepsis. Absence of the spleen was demonstrated by radioactive scanning after injection of Au(198) colloid and chromium-tagged, heated red cells, by the presence of Howell-Jolly bodies and Heinz bodies in the peripheral blood, and by failure to synthesize antibody to sheep red blood cells injected intravenously. The situation is comparable to that in infants in whom the spleen is removed in early life.


Ahmed SA, et al. Eur J Pediatr (2010) 169:315–318


Congenital isolated asplenia may be a minor form of situs abnormality or a separate entity due to a specific defect of spleen development.