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Mevalonic aciduria
Disease definition
A rare, severe form of mevalonate kinase deficiency (MKD) characterized by dysmorphic features, failure to thrive, psychomotor delay, ocular involvement, hypotonia, progressive ataxia, myopathy, and recurrent inflammatory episodes.
Summary
Epidemiology
The exact prevalence and incidence of MVA are not known. Fewer than 50 patients have been reported to date. A small proportion of patients with MKD have mevalonic aciduria (MVA), while most cases correspond to the milder phenotype known as Hyperimmunoglobinemia D with periodic fever (HIDS).
Clinical description
Onset of MVA is usually during infancy and in some severe cases antenatally. The clinical presentation is variable with cases of severe disease with significantly reduced life expectancy to milder cases with no effect on life expectancy. Infants may be born with shortened limbs and dysmorphic features (dolichocephaly, microcephaly, frontal bossing, a triangular-shaped face, down-slanting eyelids, and dysplastic or low-set ears. Affected patients may also present with marked failure to thrive, and recurrent episodes of fever (that may be fatal in infancy) possibly accompanied by hepatosplenomegaly, lymphadenopathy, abdominal pain, vomiting, diarrhea, arthralgia, myalgia, mouth ulcers, and skin eruptions. During childhood, patients may show failure to thrive, developmental delay and progressive ataxia; in later childhood or adolescence they may develop progressive ocular disorders such as uveitis, blue sclera, retinitis pigmentosa, or cataracts. Short stature and myopathy are reported in older patients.
Etiology
MVA is caused by mutations in the MVK gene (12q24). MVK encodes mevalonate kinase, which is involved in cholesterol and isoprenoid production. In patients with the severe form of MKD, enzyme deficiency is nearly complete causing the severe manifestations of the disorder. Severity usually depends on the degree of residual enzyme activity.
Genetic counseling
MKD follows an autosomal recessive pattern of inheritance. Genetic counseling should be proposed to affected families.
Management and treatment
Inflammatory attacks can often be controlled with interleukin-1 blocking agents such as canakinumab or anakinra. Severely affected patients have been seen to improve significantly upon allogeneic hematopoietic stem cell transplantation.
Detailed information
Professionals
- Summary information
- Slovak (2006, pdf)
- Review article
- Français (2008)
- English (2006)
- Clinical practice guidelines
- Français (2015)
Additional information