ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters.

The objective of this paper is to: describe the phenotype compound heterozygote for mutations in CECR1 in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa. Subsequently, two cerebral lacunar lesions were identified following a brain stroke. Clinical features improved on anti-tumour necrosis factor therapy. The first patient's sister demonstrated early-onset, long-lasting anaemia with mild biological inflammation; at the ages of 3 and 5 years, she had presented 2 acute, transient neurological events with lacunar lesions on MRI. CECR1 sequencing identified both sisters to be compound heterozygous for a p.Tyr453Cys mutation and a previously undescribed deletion of exon 7. ADA2 activity was reduced by 50%. Neutrophil-stimulated genes were not overexpressed, but interferon-stimulated genes were. The expression of a panel of other cytokine transcripts was not significantly altered. In conclusion, searching for CECR1 mutation or assessing ADA2 activity should be considered in patients with an atypical presentation of inflammatory disease.

A large national cohort of French patients with chronic recurrent multifocal osteitis.

OBJECTIVE: To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors. METHODS: One hundred seventy-eight patients were included (123 female patients and 55 male patients), with a mean ± SD age at diagnosis of 10.9 ± 2.9 years. Inclusion criteria were a diagnosis of CRMO, evidence of at least one lesion of osteitis confirmed by imaging, and development of the syndrome before age 18 years. RESULTS: Longitudinal clinical and imaging studies revealed that only 12 of 178 CRMO patients (7%) had unifocal lesions at the last medical visit. We were able to apply the clinical chronic nonbacterial osteomyelitis score to 110 of 178 patients (62%), which indicated that bone biopsy could have been avoided in 27 cases (25%). At the last medical visit, disease was in remission in only 73 of 171 patients (43%) (41% receiving therapy) after a mean ± SD of 47.9 ± 38.9 months; 44 of 171 patients (26%) experienced sequelae. Using cluster analysis, the CRMO cohort was separated into 3 homogeneous phenotypes (severe, mild, and intermediate). Patients with the severe phenotype had the worst prognosis. This group was entirely composed of male patients, most of whom had the multifocal form of CRMO and inflammatory syndrome. Patients with the mild phenotype had the best prognosis. This group was primarily composed of female patients with a unifocal form of CRMO and infrequent clavicle involvement and inflammatory syndrome. Patients with the intermediate phenotype had a good prognosis but greater reliance on treatment. This group primarily included female patients with multifocal lesions and inflammatory syndrome. CONCLUSION: This is the largest CRMO cohort described in the literature to date. Clinical evolution and imaging investigations confirmed the multifocal pattern of the disease. Three distinct subgroups of CRMO patients were distinguished, with very different prognoses.

[Update on the management of acute viral bronchiolitis: proposed guidelines of Grand Ouest University Hospitals]. / Prise en charge de la bronchiolite aiguë du nourrisson de moins de 1 an : actualisation et consensus médical au sein des hôpitaux universitaires du Grand Ouest (HUGO).

BACKGROUND AND OBJECTIVES: While our European and North American colleagues have recently updated their recommendations, the 2000 Consensus Conference remains the main guideline on management of acute viral bronchiolitis in France. We aimed to establish an updated inter-regional protocol on management of acute viral bronchiolitis in infants. METHOD: Pediatricians, pediatric pulmonologists, and emergency physicians of the Grand Ouest University Hospitals (France) gathered to analyze the recent data from the literature. RESULTS: Criteria to distinguish childhood asthma from acute viral bronchiolitis were established, then prescriptions of diagnostic tests, antibiotics, and chest physiotherapy were defined and reserved for very limited situations. Similarly, the modalities of oxygen therapy prescription and nutritional support were proposed. Finally, other therapeutics such as nebulized hypertonic saline seem promising, but their place in the treatment of acute bronchiolitis in infants remains unclear. CONCLUSION: This work has provided new proposals for management of acute viral bronchiolitis and helped standardize practices within the Grand Ouest University Hospitals. This local organization could lay the keystone for working toward guidelines initiated by learned societies at the national level.