Mevalonate kinase deficiency
| Mevalonate kinase deficiency | |
|---|---|
| Other names | Mevalonic aciduria and Hyper immunoglobulin D syndrome (HIDS) |
| A patient with mevalonate kinase deficiency at the age of 21 months, displaying characteristic craniofacial features | |
| Specialty | Hematology, neurology, immunology, medical genetics, endocrinology |
Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. It is a rare genetic disorder, but a high frequency is observed in Northern European regions.
Mevalonate kinase (MVK) is an enzyme involved in biosynthesis isoprenoids and is necessary for the conversion of mevalonate to mevalonate-5-phosphate in the presence of Mg2+
. Downstream of this enzyme, mevalonate-5-phosphate is converted into non-sterol (geranylgeranyl, farnesyl) or sterol isoprenoids (cholesterol). MKD is due to a pathogenic variants in the gene that encodes mevalonate kinase which results in a reduced or deficient activity of this enzyme. Because of this deficiency, mevalonic acid can build up in the body, with high levels found in the urine.
The severity of MKD depends on the level of this deficiency, with hyperimmunoglobulinemia D syndrome (first described as HIDS in 1984) being less severe but more common, and mevalonic aciduria (MVA) being a more severe but rarer form.