Chronic granulomatous disease (CGD) is a rare primary immune deficiency caused by mutations in genes coding for components of the nicotinamide adenine dinucleotide phosphate oxidase, characterized by severe and recurrent bacterial and fungal infections, together with inflammatory complications. Dysregulation of inflammatory responses are often present in this disease and may lead to granulomatous lesions, most often affecting the gastrointestinal (GI) and urinary tracts. Treatment of inflammatory complications usually includes corticosteroids, whereas antimicrobial prophylaxis is used for infection prevention. Curative treatment of both infectious susceptibility and inflammatory disease can be achieved by hematopoietic stem cell transplantation. We report herein three patients with the same mutation of the CYBB gene who presented with very early-onset and severe GI manifestations of X-linked CGD. The most severely affected patient had evidence of antenatal inflammatory involvement of the GI and urinary tracts. Extreme hyperleukocytosis with eosinophilia and high inflammatory markers were observed in all three patients. A Mycobacterium avium lung infection and an unidentified fungal lung infection occurred in two patients both during their first year of life, which is indicative of the severity of the disease. All three patients underwent bone marrow transplantation and recovered fully from their initial symptoms. To our knowledge, these are the first reports of patients with such an early-onset and severe inflammatory manifestations of CGD.

Postural orthostatic tachycardia syndrome (POTS) is a clinical chronic condition characterized by chronic fatigue and orthostatic symptoms associated with postural tachycardia. Early diagnosis and intervention can prevent significant functional consequences, although it can be very difficult to recognize. Two cases of POTS were presented in this article to help clinicians identify POTS more easily. Firstly, we present a 16-year-old adolescent female who was hospitalized for daily headaches, chronic fatigue, bilateral lower limbs discoloration and edema on standing position associated with orthostatic symptoms. All investigations were negative except for tilt table test, which showed heart rate increase of 80 beats per min, hypotension and discoloration of lower limbs, confirming POTS diagnosis. Non-pharmacological treatment showed no improvement. Midodrine was started because of β-blockers intolerance with only moderate response. Secondly, we present a 17-year-old patient diagnosed with benign hypermobility syndrome who was referred for recurring episodes of palpitations associated with heat, nausea, headache and vertigo for the past year. She also reported dizziness and lower limbs discoloration on standing position. Previous investigations were negative. A clinical diagnosis of POTS was made based on history. Non-pharmacologic treatments with hydration, increase of salt intake and regular exercise were tested. However, no improvement was shown. Symptoms were controlled by a propranolol trial. These cases relate a clinical sign that can be easily identified by a clinician attempting to diagnose POTS. Acrocyanosis can be unquestioned or ignored. Clinicians should be attentive to this condition, and attempt to diagnose its underlying causes. This can result in lowering unnecessary testing and interventions. Patients with dependent acrocyanosis should be closely evaluated for the diagnosis of POTS.

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Introduction: Recognition of life-threatening conditions, such as brain tumours, remains a challenge among pediatric patients. Few studies have described the implication of initial presentation, clinical evolution and healthcare system factors in diagnosis delay of brain tumours in children. We aimed to determine the clinical presentation patterns and health care trajectory of children with a diagnosis of primary brain tumour. Methods: A retrospective chart review in a pediatric university-affiliated hospital was conducted. Participants were all patients less than 18 years of age diagnosed with a brain tumour by neuroimaging between Jan 2003 and Dec 2014. Data were extracted from an institutional tumour registry and medical records. Results: From the registry, 288 patients were identified. The mean age at time of diagnosis was 7.44 ± 0.29 years. Most tumours were infra-tentorial (55%) and had astrocytic origin (29%). The majority (35%) had consulted only once prior to diagnosis, while 14% had consulted at least 4 times prior to diagnosis. The mean time between the onset of symptoms and diagnosis was 147 ± 19 days. The mean time between symptoms onset and first consultation was 84 ± 14 days. The most frequent symptoms and signs at onset and diagnosis were respectively: headache (44% vs 59%, p<0.01), nausea and vomiting (31% vs 58%, p<0.01) and abnormalities of gait (10% vs 32%, p<0.01). 129 patients (45%) were diagnosed in an Emergency Department (ED). Symptoms and signs that differed significantly for those diagnosed in an ED were: headache (71% vs 42%, p<0.01), nausea and vomiting (73 % vs 32%, p<0.01), lethargy (26% vs 9%, p<0.01), weight loss (15% vs 3%, p<0.01), irritability (9% vs 0%, p<0.01) and endocrine abnormality (2% vs 8%, p=0.02). Clinical presentations of infants up to one year of age (14%) differed from other age groups. They presented mostly with growth abnormality (46%), macrocephaly (40%), irritability (40%), development abnormalities (18%) and sun-setting eyes sign (10%). Conclusion: In this large comprehensive cohort, we have found that the diagnosis of primary brain tumours is most frequently made in the ED. Different clinical presentations have been identified and varied between different settings of diagnosis and different age groups.