Mevalonic aciduria

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Other Names:

Complete mevalonate kinase deficiency; Mevalonicaciduria; MVA

Categories:

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Musculoskeletal Diseases; RDCRN; Skin Diseases See More

Summary Summary

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

Symptoms Symptoms

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.

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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 Small head circumference Decreased size of skull Reduced head circumference [ more ]	0000252
Muscular hypotonia	Low or weak muscle tone	0001252
Seizure		0001250
Short stature	Small stature Decreased body height [ 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
1%-4% of people have these symptoms
Attenuation of retinal blood vessels	Narrowing of blood vessels in back of eye	0007843
Cerebellar atrophy	Degeneration of cerebellum	0001272
Diarrhea	Watery stool	0002014
Dysarthria	Difficulty articulating speech	0001260
Edema	Fluid retention Water retention [ more ]	0000969
Elevated C-reactive protein level		0011227
Elevated erythrocyte sedimentation rate	High ESR	0003565
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 in infancy	Faltering weight in infancy Weight faltering in infancy [ more ]	0001531
Hepatosplenomegaly	Enlarged liver and spleen	0001433
Increased circulating IgD level		0410246
Increased lactate dehydrogenase level		0025435
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Kyphoscoliosis		0002751
Leukocytosis	Elevated white blood count High white blood count Increased blood leukocyte number [ more ]	0001974
Lymphadenopathy	Swollen lymph nodes	0002716
Nuclear cataract	Yellowish cloudy center of lens	0100018
Optic disc pallor		0000543
Recurrent infections	Frequent infections Frequent, severe infections Increased frequency of infection infections, recurrent Predisposition to infections Susceptibility to infection [ more ]	0002719
Underdeveloped nasal alae	Underdeveloped tissue around nostril	0000430
Vomiting	Throwing up	0002013
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
Cerebral atrophy	Degeneration of cerebrum	0002059
Fluctuating hepatomegaly		0006564
Fluctuating splenomegaly		0006268
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Low-set ears	Low set ears Lowset ears [ more ]	0000369
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

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 1/1/2021

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

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 Treatment

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

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

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

The Sterol and Isoprenoid Diseases Consortium (STAIR) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Steroid and Isoprenoid Research Consortium (STAIR) has a registry for patients who wish to be contacted about clinical research opportunities.

For more information on the registry see: https://www.rarediseasesnetwork.org/cms/stair/Get-Involved/ContactRegistry

Organizations Organizations

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

FMF & AID Global Association
Schüracherstrasse 25a
8306 Brüttisellen
Switzerland
Telephone: +41 76 415 4010
E-mail: info@fmfandaid.org
Website: https://www.fmfandaid.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

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

Genetics Home Reference (GHR) contains information on Mevalonic aciduria. This website is maintained by the National Library of Medicine.

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.

GARD Answers GARD Answers

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

Have a question? Contact a GARD Information Specialist.

References References

Mevalonate kinase deficiency. Genetics Home Reference (GHR). April 2011; http://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency.
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.
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.
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.
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.