IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
TWO ADAMTS-13 SNP IN CHILDHOOD ONSET CONGENITAL TTP
Autor/es:
CALDERAZZO JC; POWAZNIAK Y; KEMPFER AC; HERNANDEZ LOIS G; SÁNCHEZ LUCEROS A; LAZZARI MA
Lugar:
Milan
Reunión:
Congreso; 21st International Congress on Thrombosis; 2010
Institución organizadora:
Mediterranean League on Thrombotic Diseases
Resumen:
Background/Aims: The thrombotic thrombocytopenic purpura (TTP) is a microangiopathic disease associated with ADAMTS-13 deficiency. More than 70 ADAMTS-13 gene mutations have until now been identified in inherited TTP. The majority of mutations are located at the N-terminal of ADAMTS-13, emphasizing the importance of these domains in VWF cleavage. Donadelli et al (2006), have found SNPs within exon and intron boundaries in several patients. They suggested that the interplay of SNPs could at least in part account for ADAMTS-13 functional abnormalities in patients with no mutations. We present a case of a 9-monthold male patient with microangiopathic haemolytic anaemia (Hb=8 g/dL), and thrombocytopenia (platelets= 31x109/L). A new TTP episode occurred at age of 10 month. The patient, during the follow up, was treated with plasma infusion. Methods: The patient was followed up until the age of 10 years. The methods developed were: ADAMTS-13 activity and IgG anti-ADAMTS-13 (Technozym ELISA), VWF multimers (SDS-agarose gel electrophoresis and immunoenzymatic stain) and ADAMTS-13 gene (29 exons) mutations screening (PCR/sequencing) Results: ADAMTS-13 activity= 3 U/dL (normal range= 40-130 U/dL). IgG anti-ADAMTS-13= 7 U/mL (normal range <12 U/mL). Ultralarge VWF multimers=44% (normal value <15%).The ADAMTS-13 activity of the patient’s mother was 73 U/dL. The patient was homozygous for the known SNP G354A and C88T. Patient’s mother was heterozygous for both SNP. Discussion: In conclusion, this study presents the continued heterogeneity of ADAMTS-13 gene defects. The impact of these SNPs needs to be elucidated, because these are the unique genetic defect found in the 29 exons. The SNPs alone or in combination (in homozygous state) might be responsible for the deficiency of ADAMTS-13 and the patient’s episodes of TTP.