What is Mevalonate Kinase Deficiency?
[The following essay is written by Jack C. Drda, MD/PhD University of Pittsburgh Medical Scientist Training Program: https://www.mdphd.pitt.edu/people/jack-drda. Jack C. Drda thanks Sander Houten, Associate Professor of Genetics and Genomic Sciences, Mt. Sinai for his critical review of portions of this essay.] Mevalonate Kinase Deficiency (MKD) is a rare medical condition where patients have fevers, joint pain, and inflammation. Since MKD patients can have these symptoms suddenly, MKD is defined as an “autoinflammatory” condition. (1) Genetic variants in the mevalonate kinase gene cause MKD. (2) Because of these variants, patients cannot effectively make important molecules called isoprenoids. These isoprenoid molecules are important in helping cells communicate with one another. Since MKD patients do not have enough isoprenoids, their cells communicate differently, activating inflammatory signals that are usually silenced. (3) These increased inflammatory signals are called cytokines, and its increase leads to the inflammation in MKD patients. (4) Many current treatments for MKD are called antibody therapies. These therapies bind to the cytokines, helping to prevent the “autoinflammation.” MKD is known to exist on a spectrum, with severe to more mild symptoms. (5) In the past, MKD was classified as either mild (Hyperimmunoglobulin D Syndrome, HIDS) or severe (Mevalonic Aciduria, MA). However, this naming system was dropped since it did not describe the underlying cause of the disease. (6) The gene that has these variants is called the MVK gene. The most common MVK variant is p.V377I, and MKD patient often are compound heterozygote for a more penetrant variant, such as p.H20P or p.I268T 5. More variants for the MVK are discovered every year as awareness of MKD increases and genetic testing becomes more widespread worldwide. Because of this increasing diversity in MKD, all the variants fall under the umbrella term of “Mevalonate Kinase Deficiency Spectrum Disorders.” On this spectrum, there can be “MKD-mild” or “MKD-severe.” At MKD and Me we represent and embrace this diversity with our logo. Its different colors represent the spectrum of this rare medical condition. Written by Jack Drda 1. Julie Krainer, Sandra Siebenhandl, and Andreas Weinhäusel, “Systemic Autoinflammatory Diseases,” Journal of Autoimmunity 109 (May 1, 2020): 102421, https://doi.org/10.1016/j.jaut.2020.102421. 2. Sander M. Houten et al., “Mutations in MVK, Encoding Mevalonate Kinase, Cause Hyperimmunoglobulinaemia D and Periodic Fever Syndrome,” Nature Genetics 22, (June 1999): 175–77, https://doi.org/10.1038/9691. 3. Murali K. Akula et al., “Control of the Innate Immune Response by the Mevalonate Pathway,” Nature Immunology 17, (August 2016): 922–29, https://doi.org/10.1038/ni.3487. 4. Maurizio Ceppi et al., “MicroRNA-155 Modulates the Interleukin-1 Signaling Pathway in Activated Human Monocyte-Derived Dendritic Cells,” Proceedings of the National Academy of Sciences 106, (February 24, 2009): 2735–40, https://doi.org/10.1073/pnas.0811073106. 5. Leslie A Favier and Grant S Schulert, “Mevalonate Kinase Deficiency: Current Perspectives,” The Application of Clinical Genetics 9, (July 20, 2016): 101–10, https://doi.org/10.2147/TACG.S93933. 6. Isabelle Touitou, “Twists and Turns of the Genetic Story of Mevalonate Kinase-Associated Diseases: A Review,” Genes & Diseases 9, (June 9, 2021): 1000–1007, https://doi.org/10.1016/j.gendis.2021.05.002.
Symptoms
Mouth Ulcers
Mouth Ulcers are medically known as Aphthous Stomatitis. These can be frequent, even between flares. Some people may experience Genital Ulcers once they hit puberty. It is unknown if this is more common in women than men. When seeking treatment for these ulcers, patients have reported that they have been tested for the Herpes Simplex Virus and other Sexual Health Screening examinations if they are not diagnosed in early childhood.Fatigue
People with MKD often expereience severe fatigue in between flare ups. It takes time for an individual to learn to plan their lifestyle in advance and to factor in periods of fatigue. Fatigue is more than just feeling tired. Fatigue to some individuals may feel like they cannot lift their head off a pillow and it can be associated with 'Brain Fog',Fevers
High grade fevers often combined with rigours or even febrile convulsions in childhood. Some adults may experience them still.Joint Swelling
People with MKD often experience joint swelling in their arms, knees, ankles, elbows, wrists and neck. Swelling can be painful, joints can be hot and very stiff. Mobility can be severaly affected by joint swelling.Abdominal Pain
People with MKD often experience severe abdominal pain. It has been reported that organs can be affected by inflammation and may be the main cause of the severe abdominal pain. Some individuals have experienced severe issues from scar tissue caused by inflammation, which has stuck to organs. There have been reports of emergency surgery to separate the scar tissue which has caused bowel blockages. Some individuals experience vomiting, diarrohea or constipation.Mottled Skin and Skin Rashes
People with MKD can experience mottled skin on the palms of their hands and feet. This is usually more severe during a flare. Skin rashes are also common during a flare. Individuals usually experience 'blotchy' skin rashes that can be hot and sometimes itchy.
Patient Experience
VACANT
PATIENT NAME
PATIENT INFO
"I was born with MKD and not diagnosed until I was 16 years old (2003)."
RACHEL RIMMER
Patient of MKD, 36 years old
VACANT
PATIENT NAME
PAITENT INFO