Rare Infectious Disease News

Disease Profile

Mevalonic aciduria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

E88.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Complete mevalonate kinase deficiency; Mevalonicaciduria; MVA

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

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] 

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.

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
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

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.

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

    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

      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.

        References

        1. Mevalonate kinase deficiency. Genetics Home Reference (GHR). April 2011; https://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency.
        2. Haas D, Hoffmann GF. Mevalonic aciduria. Orphanet. April 2006; https://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; https://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; https://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; https://www.nejm.org/doi/full/10.1056/NEJMc072018. Accessed 2/2/2012.

        Rare Infectious Disease News