National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Mevalonic aciduria

Mevalonic aciduria is the severe form of mevalonate kinase deficiency, a condition characterized by recurrent episodes of fever that typically begin during infancy.[1] During these fever episodes, people with mevalonic aciduria may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, joint pain (arthralgia), and skin rashes. Additional ongoing issues include developmental delay, progressive ataxia, progressive problems with vision, an unusually small, elongated head, and failure to thrive.[1][2] Mevalonic aciduria is caused by deficiency of mevalonate kinase, the first committed enzyme of cholesterol biosynthesis.[2] This deficiency occurs as a result of inherited mutations in the MVK gene.[1][2] This condition is inherited in an autosomal recessive pattern.[1] Treatment is challenging and remains mainly supportive.[2]

The less severe type of mevalonate kinase deficiency is called hyperimmunoglobulinemia D syndrome (HIDS).[1] 

Last updated: 2/6/2012

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 44 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development
[ more ] 		0002750
Dolichocephaly
Long, narrow head
Tall and narrow skull
[ more ] 		0000268
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Large fontanelles
Wide fontanelles
0000239
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Seizure 0001250
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Splenomegaly
Increased spleen size
0001744
Triangular face
Face with broad temples and narrow chin
Triangular facial shape
[ more ] 		0000325
30%-79% of people have these symptoms
Ataxia 0001251
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Low-set, posteriorly rotated ears 0000368
5%-29% of people have these symptoms
Kyphoscoliosis 0002751
Percent of people who have these symptoms is not available through HPO
Agenesis of cerebellar vermis 0002335
Arthralgia
Joint pain
0002829
Autosomal recessive inheritance 0000007
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Diarrhea
Watery stool
0002014
Edema
Fluid retention
Water retention
[ more ] 		0000969
Elevated hepatic transaminase
High liver enzymes
0002910
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase
[ more ] 		0003236
Elevated urine mevalonic acid 0032638
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Fluctuating hepatomegaly 0006564
Fluctuating splenomegaly 0006268
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Increased circulating IgD level 0410246
Leukocytosis
Elevated white blood count
High white blood count
Increased blood leukocyte number
[ more ] 		0001974
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Lymphadenopathy
Swollen lymph nodes
0002716
Morbilliform rash 0012282
Normocytic hypoplastic anemia 0004819
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Progressive cerebellar ataxia 0002073
Psychomotor retardation 0025356
Thrombocytopenia
Low platelet count
0001873
Vomiting
Throwing up
0002013
Showing of 44 |
Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment of mevalonic aciduria remains a challenge.[3] There is no standard treatment that is effective in all patients, so it remains mainly supportive.[2] Treatment with simvastatin (an inhibitor of hydroxymethylglutaryl coenzyme A reductase, the enzyme that catalyzes the formation of mevalonic acid), which has been used with guarded success in patients with HIDS, worsened the clinical status of two patients with mevalonic aciduria.[4] Anakinra, another medication used with some degree of success in HIDS patients, induced partial remission in at least one patient with mevalonic aciduria, but not all patients respond to so favorably.[3] 

Reports of successful treatment of mevalonic aciduria through allogenic bone marrow transplantation have also surfaced. At this point, this therapy is investigational and potentially applicable to patients with mevalonic aciduria whose condition is resistant to therapy with anti-inflammatory drugs (e.g., inhibitors of TNF-alpha and interleukin-1 beta).[4][5]

The following articles provide additional details regarding treatment of mevalonic aciduria.

Nevyjel M, Pontillo A, Calligaris L, Tommasini A, D'Osualdo A, Waterham HR, Granzotto M, Crovella S, Barbi E, Ventura A. Diagnostics and therapeutic insights in a severe case of mevalonate kinase deficiency. Pediatrics. 2007 Feb;119(2):e523-7.

Neven B, Valayannopoulos V, Quartier P, Blanche S, Prieur AM, Debré M, Rolland MO, Rabier D, Cuisset L, Cavazzana-Calvo M, de Lonlay P, Fischer A. Allogeneic bone marrow transplantation in mevalonic aciduria. N Engl J Med. 2007 Jun 28;356(26):2700-3.

Arkwright PD, Abinun M, Cant AJ. Mevalonic aciduria cured by bone marrow transplantation. N Engl J Med. 2007 Sep 27;357(13):1350.

Last updated: 2/2/2012

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Mevalonic aciduria. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Mevalonic aciduria. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Is enzyme therapy (utilizing a synthetic form of mevalonate kinase) available for mevalonic aciduria? See answer


  1. Mevalonate kinase deficiency. Genetics Home Reference (GHR). April 2011; http://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency.
  2. Haas D, Hoffmann GF. Mevalonic aciduria. Orphanet. April 2006; http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=403&Disease_Disease_Search_diseaseGroup=Mevalonic-aciduria&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Mevalonic-aciduria&title=Mevalonic-aciduria&searc. Accessed 2/2/2012.
  3. Bodar EJ, Kuijk LM, Drenth JP, van der Meer JW, Simon A, Frenkel J. On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis. Dec 2011; http://www.ncbi.nlm.nih.gov/pubmed/21859689. Accessed 2/2/2012.
  4. Neven B, Valayannopoulos V, Quartier P, Blanche S, Prieur AM, Debré M, Rolland MO, Rabier D, Cuisset L, Cavazzana-Calvo M, de Lonlay P, Fischer A. Allogeneic Bone Marrow Transplantation in Mevalonic Aciduria. New England Journal of Medicine. 2007; http://www.nejm.org/doi/full/10.1056/NEJMoa070715#t=articleTop. Accessed 2/2/2012.
  5. Arkwright PD, Abinun M, Cant AJ. Mevalonic Aciduria Cured by Bone Marrow Transplantation. New England Journal of Medicine. 2007; http://www.nejm.org/doi/full/10.1056/NEJMc072018. Accessed 2/2/2012.