Hereditary Thrombotic Thrombocytopenic Purpura in a Chinese Boy With a Novel Compound Heterozygous Mutation of the ADAMTS13 Gene

Abstract

Hereditary thrombotic thrombocytopenic purpura (TTP) is caused by ADAMTS13 mutations with autosomal recessive inheritance. It typically presents during childhood and is frequently misdiagnosed as immune thrombocytopenia. We present a case of hereditary TTP with an undescribed compound heterozygous ADAMTS13 mutation in a Chinese boy. A 12-year-old boy with a history of intermittent thrombocytopenia in the prior 6 years had severe deficiency of plasma ADAMTS13 and harbored a novel compound heterozygous mutation which was also identified in his sister. The c.577C>T was a pathogenic variant reported exclusively in Japanese cases. The undescribed c.2397C>A nonsense mutation was predicted to encode a truncated protein. Identification of the specific novel heterozygous ADAMTS13 mutation in the Chinese family, consisting a variant restricted to Asian individuals and an undescribed c.2397C>A nonsense mutation, demonstrates genetic diversity underlying hereditary TTP, and possibly ethnic skewed mutation profiles.

Hereditary thrombotic thrombocytopenic purpura mimicking idiopathic thrombocytopenic purpura was revealed by miscarriage——Novel Compound Heterozygous Mutations in hTTP

“…We are not the only one misdiagnosing the TTP as ITP. Patients disturbed by discontinuous thrombocytopenia were usually treated as ITP with oral steroid and remained symptom-free until an acute episode indicating TTP [12][13][14] . Although ITP is not in the list of differential diagnosis in guidelines of TTP [6][7][8][9] , ITP concurrent with intravascular hemolysis looks alike TTP [15] , and in verse, TTP in remission period showed a similar characteristic of ITP [16,17] .…”

Novel ADAMTS13 mutation in a family with three recurrent neonatal deaths: a case report and literature review

“…Researchers have suggested that USS shows mild or no clinical symptoms in childhood, and its onset is considered to be caused by various factors (e.g., pregnancy, upregulated cytokine expression during severe infection and excessive drinking) (15). In a 10-year Japanese study, 37 patients had no history of neonatal onset, and of them 29 (79%) had a history of thrombocytopenia in childhood [misdiagnosed as idiopathic thrombocytopenic purpura (ITP)], and only 16 (43%) had undergone exchange transfusion for jaundice (16).…”

A Case of Parturient with Hereditary Thrombotic Thrombocytopenic Purpura: Case Report of a Novel Variant

“…The level of ADAMST13 was less than 5% at the first test. Dai et al 17 reported a 12-year-old boy with a history of intermittent thrombocytopenia and severe ADAMTS13 plasma deficiency in the prior 6 years, and a missense mutation c.577C > T and a nonsense mutation c.2397C > A were found. The three Chinese cases were all compound heterozygous for mutations, and all of them were earlier onset.…”