Diagnosis and treatment of Mevalonate Kinase Deficiency

Mevalonate Kinase Deficiency (MKD)is a inflammatory disease, characterized by fever and inflammation in different organ systems. The disease is rare with approximately 300 known cases worldwide. This complicates the diagnosis since many physicians are unaware of the disease and its symptoms. The diagnosis can be made by genetic testing. This thesis shows that mevalonic acid in the urine can be a useful screening method to select the right patients for genetic testing. Further, this thesis described the clinical symptoms and the genetic characteristics of the largest group of MKD patients to date. Patients with specific mutations (p.V377I/p.I268T) are more at risk for a complication, AA-amyloidosis, that may lead to kidney failure. They therefore should be monitored more strictly.

The treatment of MKD can be challenging. The only evidence-based treatment is available, canakinumab. The long-term outcome of this treatment was unknown. This thesis described that canakinumab is effective as a long-term treatment. Dose increments can be necessary when canakinumab is used as a long-term treatment.

The most severely affected patients do not respond to conservative therapies. Stem cell transplantation has been described in a few cases, sometimes with promising results. This thesis described that stem cell transplantation can be effective. However, stem cell transplantation remains a risky procedure with serious morbidity and mortality.