Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Voss, R.
Management of Fanconi anemia and other Hematologically and Immunologically relevant Tumor Predisposing Syndromes in Pediatric Hematology Oncology in Austria
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2017. pp. 93
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Seidel Markus
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- Abstract:
- Chromosome instability syndromes with DNA-repair defects represent a rare group of childhood diseases with (mainly) autosomal recessive inheritance patterns. The manifestation and severity of these syndromes vary from patient to patient. They often present congenital physical abnormalities, such as microcephaly, skeletal abnormalities, abnormalities of the skin and abnormalities of the urogenital tract among others. Furthermore, progressive bone marrow failure (BMF) or immunodeficiency and predisposition to malignancy are seen in such diseases. On a molecular level, they show cellular hypersensitivity to DNA-cross linking agents and severe radio-sensitivity. The aim of this study was to determine which syndromes were represented and how many patients were affected, how their disease progressed and what therapies they received. Information from patients alive in 2000 and later was gathered directly from pediatric hematology-oncology units all over Austria. A database was created to collect patient information and serve as the basis for a future registry for chromosome instability syndromes. In 47 patients included in this study, four different syndromes were found: Fanconi anemia (FA), Ataxia telangiectasia (ATM), Nijmegen breakage syndrome (NBS) and Artemis deficiency (AD). Other syndromes, such as Bloom syndrome, constitutive mismatch repair deficiency, DNA ligase 4 deficiency or Cernunnos deficiency could not be identified. All 30 FA patients showed signs of progressive BMF, 70% of patients underwent hematopoietic stem cell transplantation (HSCT). Malignancies were observed in 57% of patients, such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and squamous cell carcinoma of head and neck (HNSCC) among others. 33% of patients died either of the consequences of HSCT or due to malignancy. ATM was diagnosed in 10 patients, six of whom suffered from severe immunodeficiency and underwent substitutional immunoglobulin therapy. Four ATM patients developed malignancy and three of four died of its consequences. Six patients were diagnosed with NBS. Five of six patients (83%) suffered from immunodeficiency, substitutional therapy was administered in 83% of patients. One patient showed autoimmunity, same patient was the only one to develop lymphoid malignancy to this point. All patients were alive. Artemis deficiency was diagnosed in one patient. This patient was diagnosed with Omenn syndrome and radio-sensitive severe combined immunodeficiency (RS-SCID) soon after birth and received curative HSCT early on. This study delivered estimates on the prevalence of these rare diseases in Austria. Furthermore, it provides data on the clinical course in the context of prophylactic and therapeutic measures such as HSCT, confirmed the heterogeneity of clinical patterns within the syndromes, stressing how crucial timely diagnosis and personalized treatment are for the wellbeing and survival of affected patients.