Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies (Muraoka et al., 1997).
King et al. (2005) proposed a new classification of CAMT ... Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies (Muraoka et al., 1997). King et al. (2005) proposed a new classification of CAMT based on the course and outcome of the disease, as exemplified by 20 patients: CAMT type I (11 patients) was characterized by early onset of severe pancytopenia, decreased bone marrow activity, and very low platelet counts. CAMT type II (9 patients) was somewhat milder and characterized by transient increases of platelet counts up to nearly normal values during the first year of life and an onset of bone marrow failure at age 3 or later.
Muraoka et al. (1997) found that a patient with CAMT had a defective response to thrombopoietin (TPO; 600044) in megakaryocyte-colony formation, decreased numbers of erythroid and myelocytic progenitors in clonal cultures, a lack of MPL mRNA in bone ... Muraoka et al. (1997) found that a patient with CAMT had a defective response to thrombopoietin (TPO; 600044) in megakaryocyte-colony formation, decreased numbers of erythroid and myelocytic progenitors in clonal cultures, a lack of MPL mRNA in bone marrow mononuclear cells, and an elevated serum level of TPO. Ihara et al. (1999) provided a follow-up of the patient reported by Muraoka et al. (1997). She was a 10-year-old girl born to nonconsanguineous Japanese parents. She appeared to be healthy at birth; however, laboratory data showed an isolated thrombocytopenia in the peripheral blood and an absence of megakaryocytes in the bone marrow. The platelet count was 2,000 in the bone marrow. Magnetic resonance imaging (MRI) of the brain showed a hypoplastic cerebellar vermis with a communication between the fourth ventricle and the cisterna magna. Despite this malformation, the child exhibited normal neurologic development and normal physical and developmental growth. The karyotype of the lymphocytes was normal. In addition to thrombocytopenia, white blood cell and red blood cell counts gradually decreased with age. At the age of 6 years, the serum TPO level was significantly higher than that in healthy controls. Ballmaier et al. (2001) analyzed 9 patients with congenital amegakaryocytic thrombocytopenia for defects in TPO production and reactivity. High levels of TPO were found in the sera of all patients; however, platelets and hematopoietic progenitor cells of patients with the disorder showed no reactivity to TPO, as measured by testing TPO-synergism to adenosine diphosphate in platelet activation or by megakaryocyte colony assays. Flow cytometry revealed absent surface expression of the TPO receptor MPL in 3 of 3 patients analyzed. Sequence analysis of the MPL gene in 8 of the patients revealed point mutations in all. Ballmaier et al. (2001) stated that a retrospective comparison of clinical data from 18 patients with CAMT from different German clinics resulted in a division into 2 different groups. Group I patients (approximately 60%) presented with a more severe form of CAMT with an early development from isolated thrombocytopenia into pancytopenia. Group II patients demonstrated a transient increase of platelet counts during the first year of life and a later development of pancytopenia. King et al. (2005) studied 20 children with CAMT, including 7 previously analyzed for TPO reactivity and MPL mutations by Ballmaier et al. (2001). Six (30%) of the 20 children died. Prognostic factors for survival were severity of thrombocytopenia and pancytopenia during the course of the disease; there was no correlation between outcome and initial platelet count. Pemberton et al. (2006) reported a British boy with CAMT confirmed by genetic analysis. He presented with thrombocytopenia in infancy, developed neutropenia at age 1 year, and progressed to full pancytopenia by age 5 years. Bone marrow biopsy was hypoplastic with markedly decreased numbers of megakaryocytes and no dysplasia. He underwent a donor hematopoietic stem cell transplant and remained well with stable engraftment at 1-year follow-up.
King et al. (2005) found that patients with the more severe CAMT type I phenotype carried nonsense MPL mutations predicted to cause a complete loss of the TPO receptor, whereas those with the milder type II phenotype carried ... King et al. (2005) found that patients with the more severe CAMT type I phenotype carried nonsense MPL mutations predicted to cause a complete loss of the TPO receptor, whereas those with the milder type II phenotype carried missense mutations in the MPL gene affecting the extracellular domain of the TPO receptor. King et al. (2005) suggested that the latter mutations likely result in proteins with residual function and a milder phenotype.
The considerable similarities between human CAMT and murine mpl deficiency prompted Ihara et al. (1999) to analyze the MPL gene in a patient with CAMT reported by Muraoka et al. (1997). MPL was not detected in her bone ... The considerable similarities between human CAMT and murine mpl deficiency prompted Ihara et al. (1999) to analyze the MPL gene in a patient with CAMT reported by Muraoka et al. (1997). MPL was not detected in her bone mononuclear cells by RT-PCR or by Northern blot analysis. By DNA studies, Ihara et al. (1999) detected compound heterozygosity for 2 mutations of the MPL gene: a gln186-to-ter substitution in exon 4 (159530.0001), and a single nucleotide deletion in exon 10 (159530.0002).