Upshaw-Schulman syndrome

Upshaw-Schulman Syndrome Upshaw-Schulman syndrome (USS) is a rare genetic disorder characterized by a deficiency in the enzyme ADAMTS13, which is crucial for blood clotting. This condition leads to a form of thrombotic thrombocytopenic purpura (TTP), a disorder that results in the formation of small blood clots throughout the body, leading to various complications.

Overview

Upshaw-Schulman syndrome is an inherited form of TTP, typically presenting in childhood. It is caused by mutations in the ADAMTS13 gene, which encodes the von Willebrand factor-cleaving protease. This enzyme is responsible for breaking down large multimers of von Willebrand factor (vWF), a protein involved in blood clotting. Without sufficient ADAMTS13 activity, these large vWF multimers persist, promoting excessive platelet aggregation and microvascular thrombosis.

Symptoms

The symptoms of Upshaw-Schulman syndrome can vary but often include:

• Thrombocytopenia: Low platelet count, leading to easy bruising and bleeding.
• Microangiopathic hemolytic anemia: Destruction of red blood cells as they pass through small, clotted blood vessels.
• Neurological symptoms: Such as headaches, confusion, or seizures due to small clots in the brain.
• Renal involvement: Kidney damage or dysfunction.

Diagnosis

Diagnosis of Upshaw-Schulman syndrome involves:

• Clinical evaluation: Assessment of symptoms and family history.
• Laboratory tests: Blood tests showing low platelet count, hemolytic anemia, and reduced ADAMTS13 activity.
• Genetic testing: Identification of mutations in the ADAMTS13 gene.

Treatment

The primary treatment for Upshaw-Schulman syndrome is plasma infusion or plasma exchange, which provides the missing ADAMTS13 enzyme. Regular plasma infusions can help prevent episodes of TTP. In some cases, immunosuppressive therapy may be used if there is an autoimmune component.

Prognosis

With appropriate treatment, individuals with Upshaw-Schulman syndrome can manage their symptoms and lead relatively normal lives. However, without treatment, the condition can be life-threatening due to the risk of organ damage from microvascular thrombosis.

Genetics

Upshaw-Schulman syndrome is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. Carriers, who have only one copy of the mutation, typically do not show symptoms.

Research

Ongoing research is focused on better understanding the genetic mutations involved in Upshaw-Schulman syndrome and developing new therapies to improve patient outcomes. Gene therapy and recombinant ADAMTS13 are areas of active investigation.

See Also

• Thrombotic Thrombocytopenic Purpura
• ADAMTS13
• Von Willebrand Factor

External Links

• National Organization for Rare Disorders
• Genetic and Rare Diseases Information Center

NIH genetic and rare disease info

• NIH info on Upshaw-Schulman syndrome

Upshaw-Schulman syndrome is a rare disease.