Congenital Thrombotic Thrombocytopenic Purpura: Atypical Presentation And First ADAMTS 13 Mutation In A Tunisian Child

Abstract

BackgroundCongenital deficiency of ADAMTS13 is characterized by systemic platelet clumping, hemolytic anemia and multiorgan failure. Although, more than 100 mutations have been reported, atypical clinical presentation may be involved in diagnostic difficulties.Case reportA 2 year old Tunisian child presented with chronic thrombopenic purpura which failed to respond to corticosteroids. Hemolytic anemia with schistocytes, occurred ten months later, with no previous history of diarrhea or any neurological abnormality. Renal function and coagulation screening tests were normal. The count of platelet improved after fresh frozen infusion (FFP). Extensive investigations revealed a severe deficiency of ADAMTS 13 activity (level< 5%). Gene sequencing identified mutation in exon 18 of ADAMTS 13 gene. Prophylactic regimen with regular infusions of FFP was associated to favorable outcome.ConclusionEarly ADAMTS 13 activity testing and gene sequencing associated to precocious plasmatherapy are recommended to reduce morbidity and mortality of congenital TTP.

Degradation of two novel congenital TTP ADAMTS13 mutants by the cell proteasome prevents ADAMTS13 secretion

“…Over 150 mutations have been identified throughout the ADAMTS13 gene in patients with congenital TTP [1,[6][7][8][9][10][11][12][13][14][15][16][17][18][19] and relationships appear to exist between ADAMTS13 genotype, age of disease onset [20] and residual ADAMTS13 activity [11]. Residual ADAMTS13 activity in turn appears to be associated with the annual rate of TTP episodes and with the requirements for fresh frozen plasma prophylaxis [11].…”

Congenital Thrombotic Thrombocytopenic Purpura: An Unusual Case of Microangiopathic Haemolytic Anaemia in a Newborn

“…[1] It was reported by Schulman in 1960 in a 8 year old child who had episode of thrombocytopenia and haemolytic anaemia since birth that responded to plasma infusion. [2] Very handful reports are there in literature particularly by Thornton KM et.al [2] , Borgi A et al [3]. TTP is a disease in which microthrombi are formed in multiple small vessels throughout the body leading to signs and symptoms of organ ischaemia, The normal coagulation process involves von Willebr and factor which is large multimeric protein which binds platelet to areas of intravascular endothelial cell damage.…”

“…Acquired TTP is more common and which is usually because of development of autoimmune antibody directed against ADAMTS13 protein. [3] The most common thrombotic microangiopathy in child is typical post diarrheal haemolytic uraemic syndrome (HUS). In HUS characteristically schistocytes appear in peripheral smear it is always a closest differential diagnosis to TTP.…”

Thrombotic thrombocytopenic purpura as a rare cause of anemia with thrombocytopenia in childhood: report of 2 cases

“…thrombocytopenic purpura (TTP) is a rare multisystem disorder characterized by single or recurrent episodes of thrombocytopenia, microangiopathic hemolytic anemia and widespread microvascular thrombosis, and may lead to ischemic multiorgan damage. 1,2 It is associated with a deficiency in the activity of "A Disintegrin and Metalloproteinase with Thrombospondin Type 1 Repeats 13" (ADAMTS-13)", a metalloproteinase which cleaves ultra large Von Willebrand Factor multimers into smaller protein fragments. There are 2 forms of the disease, congenital TTP (ADAMTS-13 gene mutations) and acquired TTP (anti-ADAMTS-13 autoantibodies and ADAMTS-13 deficiency).…”