What are the other Names for this Condition? (Also known as/Synonyms)

• Severe Mevalonic Aciduria (MA)
• Severe MKD

What is Severe Mevalonate Kinase Deficiency (Definition/Background Information)

• Severe Mevalonate Kinase Deficiency (MKD) is a rare genetic disorder caused by mutations in the mevalonate kinase (MVK) gene with autosomal recessive inheritance. The onset of the condition typically occurs during childhood. However, the disorder can affect individuals of any age group
• The signs and symptoms can vary widely but are generally severe. The common presentations include recurrent fever, abdominal pain, skin rashes, joint pain and swelling. A diagnosis of Severe Mevalonate Kinase Deficiency is made based on the clinical presentation, blood tests, and genetic testing
• The treatment mainly focuses on managing the symptoms and reducing inflammation. Treatment options may include corticosteroids and immunosuppressive medications. The prognosis of Severe Mevalonate Kinase Deficiency varies widely and mostly depends on its severity and complications that develop

Who gets Severe Mevalonate Kinase Deficiency? (Age and Sex Distribution)

• Severe Mevalonate Kinase Deficiency is an extremely rare genetic disorder that can affect individuals of all age groups. However, the symptoms typically appear in early childhood
• Most cases have been reported in individuals of Dutch or other northern European descent
• The frequency of the disorder is currently unknown. Worldwide, less than 100 cases have been reported

What are the Risk Factors for Severe Mevalonate Kinase Deficiency? (Predisposing Factors)

• The main risk factor for Severe Mevalonate Kinase Deficiency is having a family history of the disorder
• Inheriting two copies of the abnormal MVK gene, one from each parent, to develop the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider. 

What are the Causes of Severe Mevalonate Kinase Deficiency? (Etiology)

Severe Mevalonate Kinase Deficiency is caused by mutations in the mevalonate kinase (MVK) gene, leading to deficiency of mevalonate kinase enzyme.

• This gene provides instructions for making an enzyme called mevalonate kinase, which is important for the normal function of cells in the body
• In this disorder, the mutations result in a deficiency of this MVK enzyme leading to chronic inflammation and fever
• The disorder is inherited in an autosomal recessive manner. Thus, the affected individual must have two parents with the abnormal MVK gene. The parents will have no signs or symptoms from their genetic status

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Severe Mevalonate Kinase Deficiency?

The signs and symptoms of Severe Mevalonate Kinase Deficiency can vary widely, but common ones include:

• Fever lasting 4-5 days, recurring every 2-3 weeks
• Rash and other signs of inflammation that last between fevers
• Skull and facial anomalies, often noted at birth
• Seizures
• Joint pain and swelling, weak muscles
• Swelling of spleen and/or liver, abdominal pain, vomiting and diarrhea with flares
• Uveitis, cataracts, and retinal degeneration can be seen. The sclera (whites of the eye) may appear blue

How is Severe Mevalonate Kinase Deficiency Diagnosed?

Severe Mevalonate Kinase Deficiency is diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Blood tests
• Imaging studies, as needed
• Genetic testing for mutations in the MVK gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Severe Mevalonate Kinase Deficiency?

The complications of Severe Mevalonate Kinase Deficiency may include:

• Failure to thrive
• Developmental and cognitive delays, with cerebellar ataxia (gait disorder) and cerebellar atrophy
• Chronic fever with inflammation of many internal organs
• Chronic diarrhea

How is Severe Mevalonate Kinase Deficiency Treated?

The treatment for Severe Mevalonate Kinase Deficiency mainly focuses on managing the symptoms and reducing inflammation.

• Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive medications
• Biologics inhibiting activation of Interleukin-1 beta have been shown effective in some patients
  • Canakinumab is approved for this use
  • Anakinra and rilonacept, and other biologics have also been used

How can Severe Mevalonate Kinase Deficiency be Prevented?

Presently, it is not possible to prevent Severe Mevalonate Kinase Deficiency as the cause is a genetic mutation.

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of Severe Mevalonate Kinase Deficiency? (Outcomes/Resolutions)

• The prognosis of Severe Mevalonate Kinase Deficiency (MKD) varies widely, depending on the severity of the disorder
• In general, the prognosis of the disorder is much worse compared to individuals with mild/moderate MKD; serious neurological complications may be noted

Additional and Relevant Useful Information for Severe Mevalonate Kinase Deficiency:

The following link is a useful resource for information on other rare conditions on DoveMed:

https://www.dovemed.com/diseases-conditions/rare-disorders/