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

BACKGROUND

Upshaw-Schulman syndrome (USS) is rare, autosomal recessive, hereditary thrombotic thrombocytopenic purpura (TTP) caused by variants in a disintegrin-like and metalloprotease with thrombospondin type 1 motif (). USS has a heterogeneous clinical course, and most symptoms overlap with other diseases. Early diagnosis may have important implications for the patients. We found novel ADAMTS13 mutation and explored the clinical features and prognosis of newborn-onset USS to increase awareness of the disease.

CASE DESCRIPTION

The same, non-consanguineous couple had three unexplained neonatal deaths. The symptoms of the three infants were mainly severe jaundice, anemia and thrombocytopenia after birth, which was consistent with the reported USS symptoms of neonates and died rapidly suddenly in the during rescue efforts. By using whole-exome sequencing (WES) for the study family, we found a novel heterozygous compound in (c.1187 (exon10) G>A (p.C396Y)/c.1595 (exon14) G>T (p.C532F)) that was carried by the three newborns originating from father and mother respectively. We reviewed nine published studies of newborn-onset USS and compared our cases for clinical symptoms and laboratory testing. All nine published cases were diagnosed by ADAMTS13 activity; in seven cases gene mutation analysis was performed and eight cases were still alive at the time of publication.

CONCLUSIONS

The case has added clinicians' awareness of the diagnosis and treatment of USS. A novel rare mutation in broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum.