Disorders of cholesterol biosynthesis

Based on the finding of abnormally increased levels of intermediate sterol precursors in tissues and/or body fluids of patients followed by the demonstration of pathogenic mutations in genes encoding the implicated enzymes, seven distinct inherited disorders have been linked to specific enzyme defects in the isoprenoid/cholesterol biosynthetic pathway [2]. Only one of these disorders, i.e. mevalonate kinase deficiency, affects the synthesis of all isoprenoids. Patients with this disorder characteristically present with recurrent episodes of high fever and inflammation associated with abdominal pain, vomiting and diarrhoea, (cervical) lymphadenopathy, hepatosplenomegaly, arthralgia and skin rash, but may also have additional congenital anomalies.