Novel mutations in a child with congenital amegakaryocytic thrombocytopenia

Pemberton, Lucy C.; Levett, D.; Skinner, Roderick; Hall, Andrew G.; Hanley, John

doi:10.1111/j.1365-2141.2006.06358.x

Cited by 12 publications

(11 citation statements)

References 4 publications

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“…Other investigations should be performed only upon clinical suggestion to rule out the Bernard-Soulier syndrome, type II von Willebrand disease and genetic thrombocytopenia (8.9 – A) [49,50,51,52,53,54,55,56,57,58]. …”

Section: Resultsmentioning

confidence: 99%

Management of Chronic Childhood Immune Thrombocytopenic Purpura: AIEOP Consensus Guidelines

et al. 2009

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Background/Objective: The management of chronic childhood idiopathic thrombocytopenic purpura (ITP) is distinct from acute ITP. Similar to the publication on acute ITP guidelines, the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) considered it appropriate to develop consensus guidelines for chronic childhood ITP to provide useful and shared information for physicians, healthcare professionals, parents and patients. Design/Methods: A preliminary, evidence-based document issued by a select group of AIEOP pediatric hematologists was discussed, modified and approved during a Consensus Conference according to procedures previously validated by the AIEOP Board. Results: The guidelines give prominence to the periodical reevaluation of all the etiological hypotheses of thrombocytopenia in relation to its clinical condition. The majority of chronic ITP children do not require treatment, especially if bleeding is absent or minimal. The treatment decision depends on several factors other than the platelet count, and treatment options are suggested in relation to the therapeutic scenarios. Recommendations are given regarding support for surgery, particular hemorrhagic conditions, daily activities/sports, as well as for vaccines and drugs. Experimental treatments are also discussed.

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Section: Resultsmentioning

confidence: 99%

Management of Chronic Childhood Immune Thrombocytopenic Purpura: AIEOP Consensus Guidelines

et al. 2009

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“…1,[4][5][6][7][8][9][10][11] However, the diagnosis of five patients in two centers during the last 2 years raises the suspicion that the incidence of the disease is underestimated, presumably because the initial presentation of CAMT with isolated thrombocytopenia can be easily misdiagnosed with idiopathic thrombocytopenic purpura, while the late pancytopenic phase is indistinguishable from aplastic anemia. Thus, bone marrow examination should be part of the diagnostic work-up in all children with severe thrombocytopenia since birth and screening of the c-MPL gene should be performed when a reduced number of megakaryocytes is observed.…”

Section: Discussionmentioning

confidence: 99%

“…3 At least 28 different c-MPL mutated alleles have been so far identified from 32 unrelated CAMT families. 1,[4][5][6][7][8][9][10][11] Beside these mutations associated with CAMT, a gain-of-function mutation of c-MPL is responsible for familial essential thrombocythemia. 12 Interestingly, different types of mutations have been associated with different phenotypes, allowing patients to be subdivided into two groups.…”

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confidence: 99%

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations

Savoia¹,

Dufour²,

Locatelli³

et al. 2007

Haematologica

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BACKGROUND AND OBJECTIVES: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL). Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect. To improve our knowledge in this field, we studied clinical and biological features of five new patients. DESIGN AND METHODS: We diagnosed five CAMT patients, identified c-MPL mutations, including five novel alterations and investigated relationships between mutations and their clinical-biological consequences. RESULTS: In all cases, platelet c-MPL and bone marrow colonies were reduced, while serum TPO levels were elevated. We also documented that the percentage of bone marrow cells expressing tumor necrosis factor-a and interferon-g was increased during pancytopenia as compared to in controls, suggesting that, as in other bone marrow failure diseases, these inhibitory cytokines contributed to the pancytopenia. Contrary to previously published data, we found no evidence of correlations between different types of mutations and the clinical course. INTERPRETATION AND CONCLUSIONS: These results suggest that therapies, such as hematopoietic stem cell transplantation, which are potentially curative although associated with a risk of treatment-related mortality, should not be postponed even in those CAMT patients whose c-MPL mutations might predict residual activity of the TPO receptor

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“…Review of the literature identified nine cases of unrelated SCT in patients with CAMT with detailed transplant information (Table 1) (5, 8, 9, 12–14). Four additional cases were identified that have incomplete details on the age at time of transplant, HLA matching, preparative regimens and were not included in this review (15–18). All nine patients except one received a fully ablative preparative regimen with five receiving TBI.…”

Section: Discussionmentioning

confidence: 99%

Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature

Frangoul

Keates-Baleeiro

Calder

et al. 2010

Pediatric Transplantation

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CAMT is a very rare cause of thrombocytopenia in infants. Most of the patients will progress to marrow failure. Allogeneic stem cell transplant remains the only curative therapy. We present two patients with CAMT who underwent an unrelated donor bone marrow transplant, one after developing marrow failure and another early in the course of the disease. Both patients tolerated the transplant with minimal toxicity and durable engraftment. We also present a comprehensive review of the literature for unrelated donor transplant for this condition.

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Novel mutations in a child with congenital amegakaryocytic thrombocytopenia

Cited by 12 publications

References 4 publications

Management of Chronic Childhood Immune Thrombocytopenic Purpura: AIEOP Consensus Guidelines

Management of Chronic Childhood Immune Thrombocytopenic Purpura: AIEOP Consensus Guidelines

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations

Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature

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