Disorders of cholesterol synthesis

Abstract

Eight distinct inherited disorders have been linked to specific enzyme defects in the isoprenoid/cholesterol biosynthetic pathway after the finding of abnormally increased levels of intermediate metabolites in tissues and/or body fluids of patients followed by the demonstration of disease-causing mutations in genes encoding the implicated enzymes. Two of these disorders are due to a defect of the enzyme mevalonate kinase and affect the synthesis of all isoprenoids. Patients with these disorders characteristically present with recurrent episodes of high fever associated with abdominal pain, vomiting and diarrhoea, (cervical) lymphadenopathy, hepatosplenomegaly, arthralgia and skin rash, and may present with additional congenital anomalies. The remaining six enzyme defects specifically affect the synthesis of cholesterol and involve four autosomal recessive and two X-linked dominant inherited syndromes. Patients afflicted with one of these defects present with multiple congenital and morphogenic anomalies, including internal organ, skeletal and/or skin abnormalities, and/or a marked delay in psychomotor development reflecting cholesterol's pivotal role in human embryogenesis and development. © 2006 Springer Medizin Verlag Heidelberg.