BACKGROUND: The pentad of thrombocytopenia, hemolytic anemia, mild renal 
dysfunction, neurologic signs, and fever, classically characterizes the syndrome 
of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an 
acquired form but a congenital form in children has also been described. In the 
latter case, the initial presentation is often with neonatal jaundice and 
thrombocytopenia. The disorder may subsequently take a relapsing course. 
Deficiency of a recently identified novel metalloprotease, the von Willebrand 
factor (vWF)-cleaving protease, originating from mutations in the ADAMTS13 gene 
plays a major role in the development of TTP.
METHODS: Blood for DNA analysis was collected from six unrelated TTP families, 
consisting of nine patients from four different countries, and was screened for 
mutations in the ADAMTS13 gene. This gene spans 29 exons encompassing 
approximately 37 kb. Conventional techniques of DNA extraction, polymerase chain 
reaction (PCR), and direct cycle sequencing were used.
RESULTS: Eight novel ADAMTS13 mutations are presented. Half of the total number 
of mutant ADAMTS13 alleles are amino acid substitutions. The disease-causing 
mutations are spread over the gene. The pathogenicity of the individual 
mutations is based upon their predicted effect on the ADAMTS13 protein and 
segregation in family members. Although most of the patients (seven out of nine) 
had symptoms during the neonatal period, they were in a remarkably good 
condition. Only one of the nine patients had a decreased glomerular filtration 
rate (GFR) with proteinuria and hematuria. Another patient had epileptic 
seizures.
CONCLUSION: We confirm that deficiency of ADAMTS13 is a molecular mechanism 
responsible for familial TTP. An early diagnosis allows prophylactic treatment 
with fresh plasma infusions.