Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene.
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.
Department of Clinical Chemistry and Laboratory Medicine, Isala Clinics, Zwolle, The Netherlands. h.krabbe@medlon.nl.|Department of Clinical Chemistry and Laboratory Medicine, Medisch Spectrum Twente Hospital Group, Ariensplein 1, 7500, Enschede, KA, The Netherlands. h.krabbe@medlon.nl.
Johannes G
JG
Krabbe
Department of Clinical Chemistry and Laboratory Medicine, Medisch Spectrum Twente Hospital Group, Ariensplein 1, 7500, Enschede, KA, The Netherlands. evelien.kemna@medlon.nl.
Evelien W M
EW
Kemna
Department of Clinical Chemistry and Laboratory Medicine, Isala Clinics, Zwolle, The Netherlands.
Annuska L M
AL
Strunk
Department of Haematology, Isala Clinics, Zwolle, The Netherlands.
Pieter A
PA
Jobse
Department of Clinical Chemistry and Laboratory Medicine, Isala Clinics, Zwolle, The Netherlands.
P A
PA
Kramer
Department of Clinical Chemistry and Laboratory Medicine, Isala Clinics, Zwolle, The Netherlands.
L D
LD
Dikkeschei
Department of Pediatric Nephrology and Translational Metabolic Laboratory, Radboud University Medical Centre, Nijmegen, The Netherlands.
L P W J
LP
van den Heuvel
Department of Haematology, Meander Medisch Centrum, Amersfoort, The Netherlands.
Rob
R
Fijnheer
Department of Haematology, Isala Clinics, Zwolle, The Netherlands.
Leo F
LF
Verdonck
D051722:ADAM Proteins / Q000235:genetics*; D000071120:ADAMTS13 Protein; D017668:Age of Onset; D019943:Amino Acid Substitution; D005091:Exons; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics*
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
ADAMTS13; Compound heterozygosity; Congenital; Thrombotic thrombocytopenic purpura