Advances in the understanding of congenital amegakaryocytic thrombocytopenia

Abstract

SummaryCongenital amegakaryocytic thrombocytopenia (MIM #604498) is an extremely rare inherited bone marrow failure syndrome, usually presenting as a severe thrombocytopenia at birth due to ineffective megakaryocytopoiesis and no characteristic physical anomalies. Usually the isolated thrombocytopenia progresses to pancytopenia during the first years of life. The only curative therapy to date is haematopoietic stem cell transplantation. Most of the cases of congenital amegakaryocytic thrombocytopenia are caused by defective expression or function of the thrombopoietin receptor due to homozygous or compound heterozygous mutations in the gene MPL. The essential roles of thrombopoietin as a lineage specific regulator of platelet production and as a regulator of haematopoietic stem cell function are reflected in the haematological defects seen in affected individuals.

Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia

“…1 Congenital disorders account for approximately one third of cases of bone marrow failure in childhood and include many different genetic diseases, such as Fanconi anemia, dyskeratosis congenita (DC), 2 Diamond-Blackfan anemia (DBA) 3 and others. [4][5][6][7] As new genetic tests are now available to make the diagnosis of these disorders possible, their presence should be carefully considered both in children and in adults before any treatment is started. Genomic instability may result in a defect of DNA repair machinery in Fanconi anemia or telomere dysregulation in DC.…”

Flow cytometric detection of MPL (CD110) as a diagnostic tool for differentiation of congenital thrombocytopenias

“…Homozygous or compound heterozygous deleterious mutations in the MPL gene lead to congenital amegakaryocytic thrombocytopenia (CAMT). 1 The absence of MPL expression on platelets from CAMT patients has been described in a couple of case studies. 2,3 However, reduced expression of MPL on platelets has also been demonstrated in patients with other forms of congenital thrombocytopenia, 4 and in patients with inherited or acquired forms of thrombocytosis.…”

Genetic Basis of Inherited Bone Marrow Failure Syndromes

“…Missense mutations which only partially reduce receptor signaling are associated with relatively milder initial phenotype and slow progression into pancytopenia. (King, Germeshausen et al 2005;Ballmaier and Germeshausen 2009) However, the overall outcome might not be different. (Ballmaier and Germeshausen 2009) …”

“…(King, Germeshausen et al 2005;Ballmaier and Germeshausen 2009) However, the overall outcome might not be different. (Ballmaier and Germeshausen 2009) …”