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Orphanet Journal of Rare Diseases

, 1:13

First Online: 26 April 2006Received: 04 April 2006Accepted: 26 April 2006DOI: 10.1186-1750-1172-1-13

Cite this article as: Haas, D. & Hoffmann, G.F. Orphanet J Rare Dis 2006 1: 13. doi:10.1186-1750-1172-1-13


Mevalonic aciduria MVA and hyperimmunoglobulinemia D syndrome HIDS represent the two ends of a clinical spectrum of disease caused by deficiency of mevalonate kinase MVK, the first committed enzyme of cholesterol biosynthesis. At least 30 patients with MVA and 180 patients with HIDS have been reported worldwide. MVA is characterized by psychomotor retardation, failure to thrive, progressive cerebellar ataxia, dysmorphic features, progressive visual impairment and recurrent febrile crises. The febrile episodes are commonly accompanied by hepatosplenomegaly, lymphadenopathy, abdominal symptoms, arthralgia and skin rashes. Life expectancy is often compromised. In HIDS, only febrile attacks are present, but a subgroup of patients may also develop neurological abnormalities of varying degree such as mental retardation, ataxia, ocular symptoms and epilepsy. A reduced activity of MVK and pathogenic mutations in the MVK gene have been demonstrated as the common genetic basis in both disorders. In MVA, the diagnosis is established by detection of highly elevated levels of mevalonic acid excreted in urine. Increased levels of immunoglobulin D IgD and, in most patients of immunoglobulin A IgA, in combination with enhanced excretion of mevalonic acid provide strong evidence for HIDS. The diagnosis is confirmed by low activity of mevalonate kinase or by demonstration of disease-causing mutations. Genetic counseling should be offered to families at risk. There is no established successful treatment for MVA. Simvastatin, an inhibitor of HMG-CoA reductase, and anakinra have been shown to have beneficial effect in HIDS.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1172-1-13 contains supplementary material, which is available to authorized users.

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Autor: Dorothea Haas - Georg F Hoffmann


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