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2023

ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

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HYPER-IGD AND PERIODIC FEVER SYNDROME: A NEW MVK MUTATION (P.R277G) ASSOCIATED WITH A SEVERE PHENOTYPE

Joana Santos1, Juan I Aróstegui JI2, Maria João Brito3, Conceição Neves4, Marta Conde5.

1 - Área Pediatria Médica, Hospital Dona Estefânia, CHLC, EPE
2 - Immunology Department, Hospital Clínic-IDIBAPS, Barcelona, Spain
3 - Unidade de Infecciologia, Hospital Dona Estefânia, CHLC, EPE
4 - Unidade de Imunodeficiências Primárias, Hospital Dona Estefânia, CHLC, EPE
5 - Unidade de Reumatologia, Hospital Dona Estefânia, CHLC, EPE

Gene.2014 Jun 1;542(2):217-20; Publicação sob forma integral; Artigo Científico

Resumo:
Hyperimmunoglobulinemia D andperiodicfeversyndrome(HIDS; MIM# 260920) is a rare recessively-inherited autoinflammatory condition caused by mutations in theMVKgene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes offeverand inflammation. Here we report on the case of a 2 year-old Portuguese boy with recurrent episodes offever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. MutationalMVKanalysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G)mutation, while the healthy non-consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, whereas anakinra showed positive responses only at high doses. Thep.R277Gmutationhere described is a novel missenseMVKmutation, and it has been detected in this case with a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.