Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

*
(*) mandatory field





 

Other search option(s)

Congenital amegakaryocytic thrombocytopenia

Orpha number ORPHA3319
Synonym(s) CAMT
Congenital amegakaryocytic thrombocytopenic purpura
Prevalence No data available
Inheritance
  • Autosomal recessive
Age of onset Neonatal/infancy
ICD-10
  • D61.0
OMIM
UMLS
  • C1327915
MeSH
  • C535982
MedDRA -
SNOMED CT
  • 234482009

Summary

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited bone marrow failure syndrome characterized by an isolated and severe decrease in the number of platelets and megakaryocytes during the first years of life that develops into bone marrow failure with pancytopenia later in childhood.

The exact prevalence is unknown and less than 100 cases have been reported in the literature. In addition, the incidence may be underestimated due to difficult and inconsistent diagnosis of the disease.

CAMT manifests since birth, often in the first day or at least within the first month of life, with petechiae, purpura, and gastrointestinal, pulmonary or intracranial hemorrhage due to isolated thrombocytopenia and a near absence of megakaryocytes in the bone marrow. Two types of CAMT have been identified. Type I-CAMT is the severe form of the disease and is characterized by persistently low platelet counts and early progression (usually by the age of 2 years) to bone marrow aplasia associated with pancytopenia. Type II-CAMT is a milder form which presents with transient increase of platelet counts over 50x109/L during the first year of life and late (by the age of 3-6 years) or no development of pancytopenia. Cardiac defects (atrial and ventricular septal defects (see this term), abnormalities of the central nervous system (cerebral and cerebellar hypoplasia), and retardation of psychomotor development have occasionally been reported.

CAMT is due to mutations in theMPL gene (1p34) coding for Thrombopoietin (TPO) receptor (c-MPL), expressed in pluripotent hematopoietic stem cells and cells of the megakaryocyte lineage. The binding of TPO to c-MPLstimulates platelet and megakaryocyte production. Different types of mutations have been associated with different phenotypes. Nonsense mutations predicted to result in a complete loss of function of the TPO receptor lead to type I-CAMT, whereas missense mutations predicted to lead to a residual function of the receptor are associated with type II-CAMT. Cases with no defects in the MPL gene are referred to as type III-CAMT. Recently, a 21q22 deletion resulting in RUNX1 haploinsufficiency has been reported in a case of CAMT associated with various anomalies (growth retardation, hearing deficits, hernias, poor feeding).

Diagnosis is based on clinical signs, on the evidence by blood tests of thrombocytopenia (platelet count below 50x109/L) with a normal mean platelet volume and of highly elevated serum levels of TPO, and on the observation in a bone marrow aspirate of absent or very few megakaryocytes. Genetic testing can confirm the diagnosis.

The initial presentation of CAMT with isolated thrombocytopenia can be misdiagnosed as idiopathic thrombocytopenic purpura (ITP), while the late pancytopenic phase is indistinguishable from aplastic anemia (see these terms). Fanconi anemia, thrombocytopenia-absent radius (TAR), syndrome and Wiscott-Aldrich syndrome (WAS) (see these terms) should be also ruled out.

Prenatal diagnosis is possible for families in which the disease-causing mutation has been identified.

The inheritance pattern is autosomal recessive.

Management is supportive, mainly consisting of multiple platelet transfusions. At present, hematopoietic stem cell transplantation (HSCT) is the only curative therapy.

Prognosis is poor and with supportive therapy, progression to full marrow failure (tri-linear marrow aplasia) occurs during the first years of life. 30% of patients with CAMT die due to bleeding complications before the HSCT and 20% due to the HSCT.

Expert reviewer(s)

  • Pr Joan Lluís VIVES-CORRONS

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.


Captcha image
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.