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ABSTRACT: Essential thrombocythemia (ET) rarely occurs in the pediatric population and little is known about the clinical course and the molecular characteristics.
In this retrospective multi-institutional study we examine the clinical, hematological, and molecular features of 12 children aged 5-16 years with thrombocytosis and a suspected diagnosis of ET.
Median follow-up was 59 months (range 10-72). Seven patients presented with clinical symptoms potentially related to thrombocytosis. The remaining five patients were diagnosed incidentally. Median platelet count at diagnosis was 1,325 x 10(9)/L (range 600-3,050). In 11 out of 12 cases bone marrow morphology was consistent with ET, the remaining patient had chronic idiopathic myelofibrosis. Cytogenetic analyses were normal in all studied cases and only one out of nine analyzed cases harbored a JAK(V617F) allele. Within 6 months after initial presentation one patient who was initially asymptomatic developed thrombosis and another patient had mild bleeding. Eight patients were treated with acetylsalicylic acid, one patient received hydroxyurea, and two patients received anagrelide. At last follow-up, all patients were alive and none had developed leukemia. Five patients experienced hematological remission. Two children had not received any therapy. During the course of their disease, nine patients developed symptoms possibly attributable to an elevated platelet count.
In JAK2 mutation negative cases, long-term follow-up is helpful to distinguish between primary and secondary thrombocytosis. Secondary cases are not associated with organomegaly but may present with unspecific symptoms. Indications for treatment in children remain unclear.
Pediatric Blood & Cancer 08/2007; 49(1):52-5. · 1.89 Impact Factor
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ABSTRACT: Marginal zone lymphomas of MALT type comprise a considerable group of indolent B-cell non-Hodgkin lymphoma (NHL) in adult patients. In childhood, however, these tumors are extremely rare, as nearly all pediatric patients have aggressive NHL. Among 2,703 children and adolescents registered into the prospective multicenter NHL-BFM treatment studies since 1986, only 4 patients (0.1%) displayed features of MALT lymphoma. These tumors were localized in the stomach, breast, lower lid, and conjunctiva, respectively and they were associated with H. pylori infection in two patients. All children are alive but long-term follow-up will be mandatory to assess the behavior of MALT lymphoma in this age group.
Pediatric Blood & Cancer 09/2006; 47(2):210-4. · 1.89 Impact Factor
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ABSTRACT: Congenital adrenal hyperplasia is a group of autosomal recessive disorders second most often caused by deficiency of steroid 11-hydroxylase (CYP11B1) due to mutations in the CYP11B1 gene. We studied the functional and structural consequences of two novel missense mutations (W116C, L299P) and an in-frame 3-bp deletion (DeltaF438) in the CYP11B gene, detected in three unrelated families. All patients are suffering from classical CYP11B1 deficiency. In vitro expression studies in COS-7 cells revealed a decreased CYP11B1 activity in the W116C mutant to 2.9 +/- 0.9% (sd) for the conversion of 11-deoxycortisol to cortisol. The L299P mutant reduced the enzymatic activity to 1.2 +/- 0.9%, whereas the DeltaF438 mutation resulted in no measurable residual CYP11B1 activity. Introduction of these mutations in a three-dimensional model structure of the CYP11B1 protein provides a possible explanation for the in vitro measured effects. We hypothesize that the W116C mutation influences the conformational change of the 11-hydroxylase protein necessary for substrate access and product release. The L299P mutation causes a change in the position of the I helix relative to the heme group, whereas the DeltaF438 mutation results in a steric disarrangement of the heme group relative to the enzyme. Studying the enzyme function in vitro helps to understand the phenotypical expression and disease severity of 11-hydroxylase deficiency, which is the basis for accurate genetic counseling, prenatal diagnosis, and treatment. Moreover, the combination of in vitro enzyme function and molecular modeling provides new insights in cytochrome P450 structural-functional relationships.
Journal of Clinical Endocrinology & Metabolism 07/2005; 90(6):3724-30. · 6.50 Impact Factor
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ABSTRACT: Kabuki syndrome is a multiple congenital anomaly/mental retardation syndrome which often involves recurrent infections. There is cumulative evidence of an immunodeficiency in Kabuki patients. We report a 2-year-old girl with typical Kabuki syndrome, who developed acute lymphocytic leukemia. The patient showed low levels of immunoglobulins G and A and a history of recurrent infections, that might indicate an immunodeficiency leading to an increased susceptibility to cancer. The girl was treated according to BFM protocols adapted to the patient's impaired cardiac situation and severe underweight. She achieved continual complete remission. Classical and molecular cytogenetic analyzes did not detect any abnormality.
American Journal of Medical Genetics Part A 10/2003; 122A(1):76-9. · 2.39 Impact Factor
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European Journal of Pediatrics 02/2003; 162(1):59-61. · 1.88 Impact Factor
