Mevalonic aciduriaE 85.-

Mevalonic aciduria (MEVA) is caused by a homozygous or compound heterozygous mutation in the mevalonate kinase gene (MVK; 251170) on chromosome 12q24. MVK is the first key enzyme in the cholesterol biosynthesis pathway. At least 30 patients with MVA and 180 patients with HIDS(hyper IgD syndrome) have been described worldwide to date.

In most patients, the first attack is triggered by a vaccination. The disease usually occurs at a young age, in 78% in the first year of life, in all of them in childhood. In patients with complete absence of MVK, the phenotype is more severe and includes facial dysmorphism, cerebellar ataxia, marked psychomotor retardation and early death in addition to the features described above.

Psychomotor retardation, failure to thrive, progressive cerebellar ataxia, dysmorphism, progressive loss of vision and recurrent febrile episodes. Hepatosplenomegaly, lymph node swelling, abdominal symptoms, joint pain and urticarial exanthema occur during the fever episodes. Life expectancy is often limited. In HIDS(hyper-IgD syndrome), which is also based on a mutation in the mevalonate kinase gene with reduced MVK activity, only recurrent fever episodes usually occur (Zhang S 2016).

Dermatologically, morbilliform or urticarial exanthema and aphthous stomatitis have been described in MEVA. Occasionally, erysipelas-like plaques (see Fig.), erythema elevatum diutinum, IgA vasculitis and Sweet syndrome have been described (Esfandiari N et al. 2023).

The diagnosis of MVA is based on the detection of a greatly increased excretion of mevalonic acid in the urine. Increased plasma levels of immunoglobulin D (IgD) and usually also of immunoglobulin A (IgA), together with increased excretion of mevalonic acid in the urine, are important indications of the presence of mevalonic aciduria and HIDS. The diagnosis is confirmed by the detection of reduced MVK activity or pathogenic MVK gene mutations.

The interleukin-1 antagonist canakinumab is the only well-studied and effective treatment for MVA patients. In a large randomized controlled trial, 35% of patients achieved complete remission. Other therapeutic options include glucocorticoids and the IL-1 antagonist anakinra, although the evidence base for these treatments is weaker. If patients do not respond to these treatments, the biologics etanercept or tocilizumab can be used. Mildly affected patients may benefit from less expensive, less invasive treatments such as paracetamol and NSAIDs (Jeyaratnam J et al. 2020).

MVA is associated with rare long-term complications such as AA-type amyloidosis , joint contractures, abdominal adhesions, renal angiomyolipomas and severe pneumococcal infections. Frequent episodes of fever affect the quality of life of patients and caregivers in several ways and have a detrimental effect on patients' daily activities, education and occupation. Life expectancy is generally normal in HIDS , while MVA can be fatal in early childhood (Ter Haar NM et al. 2016).

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