Upshaw-Schulman-Syndrom M31.1

Upshaw-Schulman syndrome refers to the congenital, autosomal recessive inherited form of thrombotic thrombocytopenic pupura (TPP), a form of thrombotic microangiopathy. This is caused by a rare, hereditary coagulation disorder, which is caused by a severe deficiency of ADAMTS13. It is caused by mutations (over 100 mutations have been described - Resham S et al 2019) in the ADAMTS13 gene on chromosome 9q34.

The clinical picture ranges from life-threatening haemolytic crises to symptoms of chronic anaemia and thrombocytopenia to neurological deficits.

ADAMTS13 is a protease that cleaves von Willebrand factor (vWF). The vWF is formed as ultra-long multimers in the endothelium. These are cleaved by the protease ADAMTS13. The absence of the protease leads to an accumulation of vWF, which results in endothelial damage in the capillaries and extracorpuscular hemolytic anemia with various organ damage. organ damage. Different ADAMTS13 mutations may influence the severity of the clinical phenotype.

The phenotype of congenital TTP is highly variable. Depending on the mutation type and residual activity of ADAMTS13, some patients develop the disease in the neonatal period (early-onset), while others experience the first TTP episode in adulthood(late-onset), especially during pregnancy.

Clinically, TTP was originally described by a pentad of symptoms:

• microangiopathic hemolytic anemia
• thrombocytopenia
• fluctuating neurological symptoms
• Renal dysfunction
• Fever

However, TTP patients often present without the full pentad, which complicates the differential diagnosis. Similar clinical symptoms may also be present in conditions such as hemolytic uremic syndrome (HUS), HELLP syndrome, or disseminated intravascular coagulation (DIC).

In case of urgent clinical suspicion of TTP, however, life-saving plasma therapy must be started immediately, since mortality without plasma exchange/substitution is over 90%. E.g. application of fresh frozen plasma (FFP) and close monitoring of platelet counts and haemolysis parameters.

1. Ahmad R et al (2015) Upshaw-Schulman syndrome. J Coll Physicians Surg Pak 25 Suppl 2:97-99.
2. Resham S et al. (2019) Upshaw-Schulman Syndrome With c.2728C>T Mutation In ADAMTS13 Gene. J Pediatr Hematol Oncol 41:e60-e62.