Hyperimmunoglobulin D syndrome in 50% of cases is associated with mevalonate kinase deficiency which can be measured in the leukocytes.

Mevalonate kinase deficiency, also called mevalonic aciduria, is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids.

Mevalonate kinase deficiency caused by mutation of this gene results in mevalonic aciduria, a disease characterized psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises.

Mevalonate kinase deficiency causes an accumulation of mevalonic acid in the urine, resulting from insufficient activity of the enzyme mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36).

Classified as an inborn error of metabolism, mevalonate kinase deficiency usually results in developmental delay, hypotonia, anemia, hepatosplenomegaly, various dysmorphic features, mental retardation, an overall failure to thrive and several other features.