Subject(s)
Lung Diseases, Interstitial/diagnosis , Membrane Proteins/genetics , Skin Diseases, Vascular/diagnosis , Vascular Diseases/diagnosis , Age of Onset , Anemia , Antibodies, Antineutrophil Cytoplasmic/immunology , Antibodies, Antinuclear/immunology , Arthralgia/drug therapy , Arthralgia/genetics , Arthralgia/immunology , Blood Sedimentation , Bronchiectasis/diagnosis , Bronchiectasis/drug therapy , Bronchiectasis/genetics , Bronchiectasis/immunology , C-Reactive Protein/immunology , Child, Preschool , Cough , Failure to Thrive , Female , Fever/drug therapy , Fever/genetics , Fever/immunology , High-Throughput Nucleotide Sequencing , Humans , Immunoglobulin G/immunology , Immunosuppressive Agents/therapeutic use , Infant , Interferon Type I , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/genetics , Lung Diseases, Interstitial/immunology , Multiple Pulmonary Nodules/diagnosis , Multiple Pulmonary Nodules/drug therapy , Multiple Pulmonary Nodules/genetics , Multiple Pulmonary Nodules/immunology , Osteoarthropathy, Primary Hypertrophic , Sequence Analysis, DNA , Serum Amyloid A Protein , Skin Diseases, Vascular/drug therapy , Skin Diseases, Vascular/genetics , Skin Diseases, Vascular/immunology , Vascular Diseases/drug therapy , Vascular Diseases/genetics , Vascular Diseases/immunologyABSTRACT
In selected cases, childhood's recurrent fevers of unknown origin can be referred to systemic autoinflammatory diseases as mevalonate kinase deficiency (MKD), caused by mutations in the mevalonate kinase gene (MVK), previously named "hyper-IgD syndrome" due to its characteristic increase in serum IgD level. There is no clear evidence for studying MVK genotype in these patients. From a cohort of 305 children evaluated for recurrent fevers in our outpatient clinic during the decade 2001-2011, we have retrospectively selected 10 unrelated Italian children displaying febrile episodes, associated with recurrent inflammatory signs (variably involving gastrointestinal tube, joints, lymph nodes, and skin) and persistently increased serum IgD levels. All these patients were examined for MVK genotype: only 2 presented bonafide MVK mutations, 5 showed the same S52N MVK polymorphism, while the remaining 3 had a wild-type MVK sequence. Clinical details of these patients have been reviewed through the critical analysis of their medical charts. Our report underscores the pitfalls of MKD diagnosis based on clinical grounds and IgD levels, emphasizing the uncertain contribution of MVK polymorphisms in the diagnostic assessment of the syndrome.
