MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: MVK

MVK

Motor delay
Ataxia
Unsteadiness
Recurrent fever
Hepatosplenomegaly
Hypotonia
Cataracts
Anemia
Lymphadenopathy
Myopathy

Mevalonate Kinase Deficiency

Clinical Characteristics

General description (for patients): 

This is a serious multisystem disease in which few patients survive to adulthood.  Weakness, unsteadiness, recurrent fevers, floppy muscles, anemia and developmental delays are important features.  The lymph nodes, liver, and spleen are enlarged and there is an increased susceptibility to infections.

Medical description:  

MVK is a severe enzymatic deficiency causing multi-organ disease.  Hypotonia, ataxia, motor delay, anemia, and hepatosplenomegaly with lymphadenopathy are early and important features but recurrent fever is the most unusual.  Some patients have fat malabsorptive enteropathy as well.  Increased levels of mevalonic acid in urine are diagnostic.

Genetics:

Mevalonate kinase deficiency is caused by a mutation in the MVK gene located on chromosome 12 (12q24). This kinase is an important link in cholesterol and isoprenoid synthesis.  Multiple mutations have been found including 803T>C and 1174G<A mutations in the Mennonite community of Southeastern Pennsylvania.  There is some suggestion of clustering of these mutations. This is likely an autosomal recessive disease but no large pedigrees have been published. Compound heterozygosity seems to be common.

Treatment:

None has been found.  Attempts to inhibit the precursor reductase to lower tissue levels of mevalonic acid has led to patient decompensation suggesting that its accumulation is not responsible for the clinical manifestations.

Prognosis:

Few patients live to become adults.

Ancillary treatments and support:

General support as needed.

Specialists and specialty centers:

Pediatrician, neurologist, infectious disease, ophthalmologist.

References:

Hinson, D.D., Ross, R.M., Krisans, S., Shaw, J.L., Kozich, V., Rolland, M.-O., Divry, P., Mancini, J., Hoffmann, G.F., and Gibson, K.M.:  Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry.  A. J. Hum. Genet. 65: 327-335, 1999.  PubMed ID: 10417275

Mandey, S.H.L., Schneiders, M.S., Koster, J., and Waterham, H.R.:  Mutational spectrum and genotype-phenotype correlations in mevalonate kinase deficiency.  Hum. Mutat. 27: 796-802, 2006.  PubMed ID: 16835861

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