Symptoms of Congenital Amegakaryocytic Thrombocytopenia
Most people with CAMT are identified in infancy, usually shortly after birth. Similar to other conditions with thrombocytopenia, bleeding is often one of the first symptoms. Bleeding typically occurs in the skin (called purpura), mouth, nose, and gastrointestinal tract. Almost all children diagnosed with CAMT have some skin findings. The most concerning bleeding is intracranial (brain) hemorrhage, but thankfully that does not happen often.
Most inherited bone marrow failure syndromes like Fanconi anemia or dyskeratosis congenita have obvious birth defects. Infants with CAMT do not have specific birth defects associated with the condition. This can help distinguish CAMT from another condition that presents at birth called thrombocytopenia absent radius syndrome. This condition has severe thrombocytopenia but is characterized by shortened forearms.
Diagnosis
A complete blood count (CBC) test is a common blood test drawn when someone has bleeding for unknown reasons. In CAMT, the CBC reveals severe thrombocytopenia, with a platelet count usually less than 80,000 cells per microliter without anemia (low red blood cell count) or changes in the white blood cell count. There are numerous reasons for a newborn infant to have thrombocytopenia, so the workup will likely include ruling out multiple infections, such as rubella, cytomegalovirus, and sepsis (severe bacterial infection). Thrombopoietin (also called megakaryocytic growth and development factor) is a protein that stimulates platelet production. Thrombopoietin levels in people with CAMT are elevated.
After more common causes of thrombocytopenia are ruled out, a bone marrow biopsy may be required to assess platelet production. The bone marrow biopsy in CAMT will reveal almost a complete absence of megakaryocytes, the blood cell that produces platelets. The combination of severely low platelet count and absence of megakaryocytes is diagnostic for CAMT. CAMT is caused by mutations in the MPL gene (thrombopoietin receptor). It is inherited in an autosomal recessive fashion, meaning both parents have to carry the trait for their child to develop the condition. If both parents are carriers, they have a 1 in 4 chance of having a child with CAMT. If desired, genetic testing can be sent to look for mutations in the MPL gene, but this testing is not required to make the diagnosis.
Treatment
Initial treatment is directed at stopping or preventing bleeding with platelet transfusions. Platelet transfusions can be very effective, but risks and benefits should be carefully weighed, since some people who receive multiple platelet transfusions can develop platelet antibodies, reducing the effectiveness of this treatment. Although some forms of thrombocytopenia can be treated with thrombopoietin, because people with CAMT do not have enough megakaryocytes to make platelets adequately, they do not respond to this treatment.
Although only platelets are affected initially, over time anemia and leukopenia (low white blood cell count) can develop. This lowering of all three blood cell types is called pancytopenia and may result in the development of severe aplastic anemia. This usually occurs between 3-4 years of age, but may occur at an older age in some patients.
The only curative therapy for amegakaryocytic thrombocytopenia currently is stem cell (or bone marrow) transplantation. This procedure uses stem cells from closely matched donors (usually a sibling if available) to resume blood cell production in the bone marrow.
A Word From Verywell
Finding out your baby has a chronic medical condition shortly after birth can be devastating. Fortunately, platelet transfusions can be used to prevent bleeding episodes and stem cell transplants can be curative. Talk to your child’s physician about your concerns, and make sure you understand all the treatment options.
