Abstract
Upshaw-Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic purpura (TTP) characterized by a deficiency of ADAMTS13 activity due to its mutations. More than half of USS patients have an episode of severe jaundice during the newborn period and require exchange blood transfusions. Beyond this period, however, the clinical manifestations of USS vary significantly from patient to patient, and do not usually include Moschowitz’s pentad, a hallmark of TTP. However, a consistent clinical sign in these patients is an occasional or chronic thrombocytopenia that is enhanced by precipitating factors such as viral infections. Therefore, USS patients are often incorrectly diagnosed with idiopathic thrombocytopenic purpura (ITP) or Evans syndrome during childhood, and the underlying ADAMTS13 gene defects are overlooked.
Here, we report on 7 female USS patients belonging to 4 different families, including 3 pairs of siblings who were uniformly diagnosed by episodes of thrombocytopenia or prevalence of TTP at 5~6 months of pregnancy. Plasma ADAMTS13 activity was measured with a highly sensitive ELISA using a monoclonal antibody directed against the VWF-A2 domain developed in our laboratory. The ADAMTS13 activity and gene mutations in these patients are described:
Family K: an elder sister K1 (activity 0.69%; gene mutation Y304C/G525D) and a younger sister K2 (activity <0.5%; gene mutation Y304C/G525D),
Family L: an elder sister L1 (activity 1.3%; gene mutation 372insGT/Q1302X) and a younger sister L2 (activity 0.96%; gene mutation 372insGT/Q1302X),
Family M: an elder sister M1 (activity <0.5%; gene mutation R193W/R349C) and a younger sister M2 (activity <0.5%; gene mutation R193W/R349C), and
Family O: a patient (activity <0.5%;gene mutation I178T/Q929X). Figure indicates family pedigree of USS involved in this study.
Family pedigree of Upshaw-Schulman syndrome
