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Some 300 cases of mevalonate kinase deficiency (MKD) have been reported worldwide. Many cases are probably not diagnosed, implying that prevalence may be higher than expected. Males and females are affected equally.

All patients suffer from recurrent inflammatory episodes with fever, pain, diarrhea, skin eruptions, and headache. Patients with the more severe phenotype, mevalonic aciduria (MVA), can also exhibit developmental, neurological and ophthalmological involvement. MKD develops antenatally, during infancy, or in childhood and covers a clinical spectrum ranging from a relatively mild periodic fever disorder to a lethal metabolic disease. There are two types of MKD depending on the severity of the clinical manifestations: Hyperimmunoglobinemia D syndrome (HIDS) with periodic episodes of fever lasting 3 to 7 days, and MVA which includes dysmorphic features, failure to thrive, developmental delay, progressive ataxia, psychomotor delay, progressive ocular manifestations, short stature, and myopathy later in life.

MKD is caused by mutations in the MVK gene (12q24), which encodes mevalonate kinase involved in cholesterol and isoprenoid production. The exact pathogenesis is currently unclear. Enzyme deficiency results in impaired cholesterol biosynthesis and increased production of inflammatory mediators. The residual enzyme activity is correlated with the severity of the manifestations with HIDS patients having a residual activity between 1.8% and 28%, while MVA patients have enzyme activities below 0.5%. However, overlap between both phenotypes may occur. No clear genotype-phenotype correlations have been identified.

MKD follows an autosomal recessive pattern of inheritance.