RESUMEN
UNLABELLED: We report on the fatal clinical course of a 3 year old male Turkish patient suffering from osteopetrosis caused by a homozygous mutation in the chloride channel gene ClCN7 with developing pancytopenia and severe neurological impairment. Hepatosplenomegaly due to extramedullary hematopoesis, severe transfusion-dependent anemia and growth failure initially suggested metabolic or oncologic disorder. Particular haematological parameters like tear drop cells basophilic punctation of the polymorphonuclear cells in the absence of haemolysis caused the diagnostic X-ray investigations of the skull and vertebral column. Raised serum creatinkinase-BB isoenzyme and genetic testing were in line with the diagnose of osteopetrosis at an age of 2(1/2) years. CONCLUSION: Osteopetrosis is a rare but considerable differential diagnose for unclarified change in haematopoetic cell lines combined with severe neurological symptoms mimicking metabolic or haematological disease. Because of this rare disease a consensus protocol for diagnostics, treatment and follow up of patients suffering from osteopetrosis is recently worked out from the European Group of Blood and Marrow Transplantation (EBMT) and the European Society for Immundeficiencies (ESID) to build up a central registry for this disease (available by ansgar.schulz@uniklinik-ulm.de).
Asunto(s)
Canales de Cloruro/genética , Análisis Mutacional de ADN , Hematopoyesis Extramedular/genética , Homocigoto , Enfermedades Neurodegenerativas/genética , Osteopetrosis/genética , Fosfatasa Alcalina/sangre , Preescolar , Aberraciones Cromosómicas , Codón/genética , Forma BB de la Creatina-Quinasa/sangre , Diagnóstico Diferencial , Epilepsia/diagnóstico por imagen , Epilepsia/genética , Exones/genética , Resultado Fatal , Genes Recesivos/genética , Humanos , Masculino , Enfermedades Neurodegenerativas/diagnóstico por imagen , Osteopetrosis/diagnóstico por imagen , Radiografía , Cráneo/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagenRESUMEN
Chronic immune thrombocytopenia (cITP) is often associated with an underlying predisposition towards autoimmunity, recognition of which is relevant to guide treatment. International recommendations on diagnostic steps and therapeutic measures of cITP in childhood exist. However, due to the low prevalence (1-2/100,000) and a variation of availability of immunological and hematological tests and treatments across pediatric units, we postulated that these guidelines are not uniformly adhered to and that immune dysregulation syndromes remained undiscovered. To delineate the current management of children and adolescents with cITP in Austria, we performed a nationwide cross-sectional study. Between 2011 and 2014, 81 children with cITP were seen at seven centers (median age 8.75 years; range 1-17; female:male ratio 47:34) at 641 visits during 180 patient years after diagnosis of cITP (>12 months ITP duration). Additional diagnoses were noted, most frequently immune or autoimmune disorders, hematologic diseases, or infections (in 37.3%, including Evans syndrome, autoimmune lymphoproliferative syndrome, systemic lupus erythematosus, and Fanconi anemia), or other symptoms like bi- or pancytopenia (n=9), lymphoproliferation or granulomatous inflammation (n = 3). Both decision to treat as well as choice of treatment varied: smaller centers tended to observe more frequently, larger centers applied a pattern of treatment modalities that appeared to depend less on bleeding tendency than on center policy. More than 50% of therapeutic interventions occurred in bleedings scores ≤2 (of 5), suggesting a strong psychosocial intention to treat. Platelet increment upon 479 therapeutic interventions of eight types was evaluated, with multiple treatment approaches being pursued sequentially in refractory patients. These data confirm the hypothesis of heterogeneous diagnostic and therapeutic management of cITP in Austrian children and corroborate the need for (1) a precise panel of parameters to exclude underlying disorders and (2) for biomarkers to predict treatment response.
Asunto(s)
Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Austria , Niño , Preescolar , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Lactante , MasculinoRESUMEN
OBJECTIVE: To investigate if the factor V Leiden mutation (F-V-LM) and/or the prothrombin gene G 20210 A variant (P-G20210A-V) are risk factors for acute stroke in Austrian children. PATIENTS: 33 children with acute ischemic stroke documented by computer tomography and/or magnetic resonance imaging of the brain were enrolled in an open multicenter survey. RESULTS: 6/33 children had F-V-LM (5 heterozygous, 1 homozygous). This represents 18% (95% CI: 6.7-39.9%) of our pediatric stroke population and thus exceeds the expected prevalence in the Austrian population of 4,6% (Fischer's exact test, p = 0.01). F-V-LM was not found in 11 children with neonatal stroke but in 6/22 children with stroke after the neonatal period. 5/6 children with F-V-LM had an underlying disorder that is a risk factor for stroke in children. The P-G20210A-V was detected in 1/26 (3.85%; 95% CI: 0.1-21.4%) patients. Comparison of the prevalence of P-G20210A-V in our study with that in the general population of Austria of 1% revealed no statistical significance (Fischer's exact test, p = 0.38). CONCLUSION: Our data suggest that the F-V-LM is a risk factor for acute stroke in Austrian children beyond the neonatal period. The P-G20210A-V apparently does not represent a risk factor for stroke in Austrian children.