Scientists from Australia and the Netherlands have identified a diagnostic biomarker of a rare childhood disease called mevalonate kinase deficiency (MKD). The study “Defective protein prenylation is a diagnostic biomarker of mevalonate kinase deficiency” is published online 10 May 2017 in the Journal of Allergy and Clinical Immunology.
MKD is a rare, inherited auto-inflammatory disease that disrupts the production of cholesterol and isoprenoids. The disease is most often caused by mutation of the MVK gene. This gene provides instructions for making the mevalonate kinase (MVK) enzyme, which plays an important role in the synthesis of cholesterol and isoprenoids. Patients usually experience recurrent episodes of high fever, which typically begin during infancy and can persist into adulthood. The severity of the disease varies from person to person. There two types of MKD: hyperimmunoglobulinemia D syndrome (HIDS) and mevalonic aciduria (MVA).
The new study provides new insights into MKD. The team, consisting of scientists from Garvan Institute of Medical Research, University of Queensland, St Vincent's Hospital, Sydney Children's Hospitals Network, and Radboud University Medical Center Australia and, found that a group of untethered proteins builds up in the cells of children with MKD. These defective proteins could be a diagnostic biomarker of MKD.
Professor Mike Rogers, who led the study, and colleagues analyzed blood cells from patients with MKD. Results showed that several Rab proteins did not have an isoprenoid 'tail', a molecule that is generally added to these proteins so that they can perform their functions. It is suspected that this tail may keep Rab proteins in a particular area of the cell. When the tail is lost, the Rab proteins become free to move to other parts of the cell, which the researchers believed might be the cause of inflammation in MKD.
The researchers developed an accurate method to detect untethered Rab proteins in blood samples, which enabled them to identify the accumulation of untethered Rab proteins in MKD cells. By contrast, this accumulation was absent in healthy controls and patients with other autoinflammatory diseases. The researchers noted that Rab proteins “appears to be a sensitive and specific diagnostic biomarker to distinguish MKD from other autoinflammatory diseases.” (Cusabio offers MVK and Rab related proteins and polyclonal antibody.)
Scientists have known for a while that the enzyme MVK is essential for the synthesis of the isoprenoid lipid geranylgeranyl diphosphate and that the gene MVK is altered in MKD. But this study provides the first clear evidence that patients with MKD could have untethered Rab proteins that lack isoprenoid tail. This would aid in the diagnosis of MKD.
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