TY - JOUR T1 - Different presentations of mevalonate kinase deficiency: a case series. JF - Clin Exp Rheumatol Y1 - 2015 A1 - De Pieri, Carlo A1 - Taddio, Andrea A1 - Insalaco, Antonella A1 - Barbi, Egidio A1 - Lepore, Loredana A1 - Ventura, Alessandro A1 - Tommasini, Alberto KW - Age Factors KW - Bacterial Infections KW - Child KW - Child, Preschool KW - Diagnosis, Differential KW - Diagnostic Errors KW - Female KW - Genetic Predisposition to Disease KW - Humans KW - Infant KW - Inflammatory Bowel Diseases KW - Male KW - Mevalonate Kinase Deficiency KW - Phenotype KW - Predictive Value of Tests KW - Recurrence KW - Risk Factors KW - Sepsis KW - Vasculitis KW - Young Adult AB -

OBJECTIVES: We aimed to raise awareness among paediatricians and physicians about this often misunderstood condition.

METHODS: We discussed the clinical profiles associated with late or wrong diagnosis of mevalonate kinase deficency (MKD) in a single centre case series.

RESULTS: We analysed the most common challenges and pitfalls that a clinician might face during the diagnostic process. Five main clinical profiles were characterised.

CONCLUSIONS: We propose a new perspective on MKD, suggesting that the presentation of this disease can vary from patient to patient.

VL - 33 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25897835?dopt=Abstract ER - TY - JOUR T1 - Genetic profiling of autoinflammatory disorders in patients with periodic fever: a prospective study. JF - Pediatr Rheumatol Online J Y1 - 2015 A1 - De Pieri, Carlo A1 - Vuch, Josef A1 - De Martino, Eleonora A1 - Bianco, Anna M A1 - Ronfani, Luca A1 - Athanasakis, Emmanouil A1 - Bortot, Barbara A1 - Crovella, Sergio A1 - Taddio, Andrea A1 - Severini, Giovanni M A1 - Tommasini, Alberto KW - Adolescent KW - Carrier Proteins KW - Child KW - Cryopyrin-Associated Periodic Syndromes KW - Cytoskeletal Proteins KW - Familial Mediterranean Fever KW - Female KW - Fever KW - Gene Expression Profiling KW - Genotype KW - Hereditary Autoinflammatory Diseases KW - Humans KW - Intracellular Signaling Peptides and Proteins KW - Logistic Models KW - Male KW - Mutation KW - Phosphotransferases (Alcohol Group Acceptor) KW - Prospective Studies KW - Receptors, Tumor Necrosis Factor, Type I KW - Syndrome AB -

BACKGROUND: Periodic fever syndromes (PFS) are an emerging group of autoinflammatory disorders. Clinical overlap exists and multiple genetic analyses may be needed to assist diagnosis. We evaluated the diagnostic value of a 5-gene sequencing panel (5GP) in patients with undiagnosed PFS.

METHODS: Simultaneous double strand Sanger sequencing of MEFV, MVK, TNFRSF1A, NLRP3, NLRP12 genes was performed in 42 patients with unexplained PFS. Clinical features were correlated with genetic results.

RESULTS: None of 42 patients analyzed displayed a causative genotype. However, single or multiple genetic variants of uncertain significance were detected in 24 subjects. Only in 5 subjects a definite diagnosis was made by taking into account both genetic and clinical data (2 TRAPS syndrome; 2 FMF; 1 FCAS). Statistical analysis showed that patients carrying genetic variants in one or more of the five selected genes displayed a significantly lower response to glucocorticoids compared with subjects who had completely negative genetic results.

CONCLUSIONS: The sequencing of multiple genes is of little help in the diagnostics of PFS and can often lead to results of uncertain interpretation, thus the clinically driven sequencing of single genes should remain the recommended approach. However, the presence of single or multiple genetic variants of uncertain significance, even if not allowing any specific diagnosis, correlated with a poorer response to glucocorticoids, possibly indicating a multifactorial subgroup of PFS with differential response to pharmacological treatment.

VL - 13 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25866490?dopt=Abstract ER - TY - JOUR T1 - Clinical significance of hyper-IgA in a paediatric laboratory series. JF - Arch Dis Child Y1 - 2014 A1 - Copetti, Valentina A1 - Pastore, Serena A1 - De Pieri, Carlo A1 - Radillo, Oriano A1 - Taddio, Andrea A1 - Ventura, Alessandro A1 - Tommasini, Alberto KW - Adolescent KW - Child KW - Child, Preschool KW - Female KW - Hospitals, Pediatric KW - Humans KW - Hypergammaglobulinemia KW - Immunoglobulin A KW - Infant KW - Italy KW - Male KW - Tertiary Care Centers AB -

The causes of extremely elevated IgA, whether isolated or associated with an increase in other classes of immunoglobulin, are poorly defined in paediatrics. We reviewed the diagnostic significance of very high IgA levels (greater than 3 SD above the mean for age) in a cohort of patients referred to a tertiary care children's hospital. Hyper-IgA was found in 91 of 6364 subjects (1.4%) and in 68 cases was not associated with an increased IgG and/or IgM level. Most subjects with hyper-IgA (73.5%) had a severe immune defect, a chronic rheumatic disease or inflammatory bowel disease, while these conditions were very rare in a control group with normal IgA values (8%). Although our results may in part reflect the experience of a tertiary care centre, we suggest that hyper-IgA in children should always arouse suspicion of a serious disease.

VL - 99 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25053738?dopt=Abstract ER - TY - JOUR T1 - F402L variant in NLRP12 in subjects with undiagnosed periodic fevers and in healthy controls. JF - Clin Exp Rheumatol Y1 - 2014 A1 - De Pieri, Carlo A1 - Vuch, Josef A1 - Athanasakis, Emmanouil A1 - Severini, Giovanni Maria A1 - Crovella, Sergio A1 - Bianco, Anna Monica A1 - Tommasini, Alberto KW - Cryopyrin-Associated Periodic Syndromes KW - Female KW - Humans KW - Intracellular Signaling Peptides and Proteins KW - Male KW - Mutation VL - 32 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25327218?dopt=Abstract ER -