Objective: To assess the impact of the COVID-19 pandemic and lockdown measures on the presenting characteristics (age at diagnosis, severity, monthly distribution) of newly diagnosed type 1 diabetes in Spanish children. Research Design and Methods: An ambispective observational multicenter study was conducted in nine Spanish tertiary-level hospitals between January 2015 and March 2021. Inclusion criteria: new cases of type 1 diabetes in children (0–14 years) recording age, sex, date of diagnosis, presence of diabetic ketoacidosis (DKA) at onset, and severity of DKA. Data were compared before and during the pandemic. Results: We registered 1444 new cases of type 1 diabetes in children: 1085 in the pre-pandemic period (2015–2019) and 359 during the pandemic (2020–March 2021). There was a significant increase in the group aged ≤4 years in the pandemic period (chi-squared = 10.986, df 2, p = 0.0041). In 2020–2021, cases of DKA increased significantly by 12% (95% CI: 7.2–20.4%), with a higher percentage of moderate and severe DKA, although this increase was not significant. In 2020, there was a sharp decrease in the number of cases in March, with a progressive increase from May through November, higher than in the same months of the period 2015–2019, highlighting the increase in the number of cases in June, September, and November. The first three months of 2021 showed a different trend to that observed both in the years 2015–2019 and in 2020, with a marked increase in the number of cases. Conclusions: A change in monthly distribution was described, with an increase in DKA at onset of type 1 diabetes. No differences were found in severity, although there were differences in the age distribution, with an increase in the number of cases in children under 4 years of age.

3600 mg/dl; IgM 126 mg/dl), elevated serum amyloid A levels (160 mg/ml) and decreased CD4/CD8 T cell ratio. Autoantibody (ANA, ENA, anti-DNA) and HLA B 27 were negative. WES analysis showed the de novo heterozygous missense variation c.C1132A (p.H378N) in PIM-1 gene (NM_001243186). This variation was never described in on-line database (HGMD, Exac, 1000 g, ESP6500). The second patient was an adult female with a clinical history of persistent microcytic anemia, splenomegaly, striking hypergammaglobulinemia (IgG > 3000 mg/dL) and recurrent protracted fever episodes during childhood. At 13 years, she underwent splenectomy because of hypersplenism. At 28 years she presented a cerebral oligoastrocytoma that was removed by surgery. No mutations were found in genes associated with autoimmune lymphoproliferative syndromes and histiocytosis (FAS, FASLG, XIAP, TNFRSF13B, UNC13D, CASP9, CASP10). The direct sequencing of PIM-1 revealed again the above described de novo mutation in PIM-1. Conclusion:We propose that these patients represent two cases of a novel syndrome associated with a specific mutation in PIM-1 gene (PLAS). First, the two cases share significant overlap of autoinflammatory and proliferative features involving the endothelial and the immune systems. Second, the gene mutation identified was never described in healthy people or in patients with other disorders and is predicted to be pathogenic based on all the bionformatic tools. Finally, previous functional studies showed that PIM-1 pathway is relevant to immune activation and indeed somatic mutations in this gene have been reported in association with lymphomas, and it is thought to contribute to survival of cancerous cells. Disclosure of Interest None Declared O6Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset systemic autoinflammatory disease

Introduction: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a non Mendelian autoinflammatory disorder until now considered to be specifically limited to paediatric age. However there is recently mounting evidence that children older than 5 years and adults may present with the typical picture of PFAPA syndrome. Objectives: We report the case of a 17,5 years old girl presenting with recurrent episodes of fever starting at the age of 16. Methods: A 17,5 years old girl was referred to our department due to recurrent episodes of fever lasting 3-4 days and starting 1,5 year ago. Body temperature usually increased up to 40.5∘C. Fever was accompanied by exudative pharyngitis, cervical lympadenopathy, severe malaise and myalgias/artralgias. Oral apthosis was present in some of the episodes. There was no other sign of upper respiratory tract infection. Headache and fatigue were evident 2-3 days before each flare.The episodes recurred very regularly showing an almost clockwork periodicity (every 35-40 days). The girl was completely asymptomatic between flares with normal growth and development. The girl's mother suffered from similar episodes of exudative pharyngitis until approximately the age of 12. Results: Laboratory exams during febrile attacks showed mild leukocytosis with prominence of neutrophils and a significant increase of monocytes. Erythrocyte sedimentation rate,C-reactive protein and Serum Amyloid A were also raised. Serum immunoglobulin levels (including IgD) were normal. During episodes all the cultures were negative.Inflammatory markers were completely normal between attacks.The girl was diagnosed with PFAPA syndrome based on Marshall criteria revised by Thomas et al.,neglecting the item of disease onset before the age of five. Genetic testing for FMF is pending. Tonsillectomy was not proposed as a therapeutic option because it seems not to be effective in adults, based on current literature. A single dose of prednisone (1 mg/ kg) given a few hours after the onset of fever dramatically abrupted fever attack in a few hours, supporting the diagnosis of PFAPA.The girl did not experience a free interval shortening after steroid administration. Conclusion: Once thought to be exclusive of the pediatric age, it is nowadays clear that PFAPA syndrome may have its onset in adulthood. Clinical features of PFAPA adults are overlapping with those of PFAPA children.To date, it is not known whether adults with PFAPA syndrome may spontaneously undergo clinical remission, and tonsillectomy does not seem to be a valid option in these patients. The description of PFAPA syndrome in adults should increase awareness among clinicians and suggests that the age criterion (i.e., age at onset less than 5 years) should not be considered mandatory for diagnosis Disclosure of Interest None Declared Disease outcome B2 Case of paraneoplastic arthritis in child