Madrid Newborn Sickle Cell Disease Cohort: clinical outcomes, stroke prevention and survival.

In May 2003, Madrid established the universal newborn screening (NBS) for sickle cell disease (SCD). However, there are no studies resembling the evolution of a SCD neonate cohort followed according to national guidelines in Spain. The aim of this study is to describe the morbimortality and the stroke prevention programme in patients diagnosed by SCD NBS in Madrid. This is a multicentre, observational, prospective cohort study between 2003 and 2018; 187 patients diagnosed with SCD were included (151 HbSS, 6 HbSß0, 27 HbSC, 3 HbSß +), and median follow-up was 5.2 years (0.03-14.9). There were 5 deaths: 2 related to SCD in patients with severe genotype (HbSS/HbSß0). Overall survival reached 95% and SCD-related survival 96.8%. The most frequent events were fever without focus, vaso-occlusive crises and acute chest syndromes. Eight strokes occurred in 5 patients which led to a 90.7% stroke-free survival in severe genotype patients (first stroke rate, 0.54 per 100 patient-years). Transcranial Doppler (TCD) was performed in 95% of eligible patients; 75% of children with pathological TCD remained stroke-free. Regarding HbSS/HbSß0 patients, 50.1% received hydroxyurea and 9.5% haematopoietic stem cell transplantation. This study reflects the evolution of Madrid SCD cohort and provides morbimortality data similar to other developed countries.

Unexpected Cause of Persistent Microcytosis and Neurological Symptoms in a Child: Niemann-Pick Disease Type C.

Atypical microcytic anemias are rare diseases of iron/heme metabolism that can be diagnostically challenging. We report the case of a 2-year-old twin boy with neurodevelopmental delay and persistent microcytosis in whom atypical microcytic anemias was initially suspected. He had low blood iron and transferrin saturation with normal/high ferritin despite iron therapy. Hemoglobinopathies were excluded by conventional/DNA studies. Hepcidin was high but iron-refractory-iron-deficiency anemia was ruled out by a genetic panel. Bone marrow aspiration revealed foamy cells and iron depletion. A genetic study confirmed the diagnosis of Niemann-Pick disease type C which was finally considered the origin of microcytosis through anemia of chronic disease.

Beta-Spectrin Deletion Responsible for Hereditary Spherocytosis: When New Technologies Are Not the Key to Success.

Hereditary spherocytosis arises from alterations in the genes encoding red blood cell membrane proteins. Although its diagnosis is mostly clinical, recent advances in next-generation sequencing (NGS) technologies have allowed for a faster cost-effective gene-based diagnosis. We report the case of a boy with spherocytic anemia and development delay in whom a de novo 2.84-Mb deletion at chromosome 14 including SPTB (ß-spectrin gene) was identified by array-based comparative genomic hybridization. This alteration, consistent with de novo spherocytosis, was missed by a NGS gene panel. When associated with other symptoms, especially neurologic, NGS may not be appropriate to genetically diagnose spherocytic anemia.

Takayasu's arteritis in an adolescent with fever of unknown origin: the contribution of PET-CT in the diagnosis.

Finding the cause of fever of unknown origin can sometimes be a real challenge. We present an adolescent whose diagnosis was achieved after 4 months of fever onset by performing a positron emission tomography (PET)-CT. A young woman presented with prolonged, intermittent fever along with inflammatory and iron deficiency anaemia, loss of weight and abdominal and chest pain. First investigational studies showed high-titre positive antinuclear antibodies, extractable nuclear antibodies and anti-Sjögren's-syndrome-related antigen a autoantibodies (anti-SSA), and mild pericardial effusion and aortic regurgitation, but without meeting criteria for systemic lupus erythematosus. She had maxillary sinusitis that did not resolve with antibiotics. Further study displayed elevated calprotectin in faeces. After normal abdominal ultrasound and CT, an intestinal MRI showed thickening of the terminal ileum, orienting towards an inflammatory bowel disease. A colonoscopy showed only minor macroscopic changes. A PET-CT scan was finally requested, which exhibited a diffuse increase in metabolism in the wall of the thoracic and abdominal aortas, suggesting Takayasu's arteritis.

[Deferasirox and Complex Proximal Tubulopathy. Presentation of two clinical cases]. / Deferasirox y Tubulopatía Proximal Compleja. Presentación de dos casos clínicos.

INTRODUCTION: Treatment with iron chelators is essential for patients with iron overload secondary to repeated trans fusions. Deferasirox is the first once-daily oral active iron chelator. As a result, therapeutic adherence has improved, reducing the complications of iron overload, especially heart failure. However, it is not exempt from possible side effects, such as kidney involvement, which is more frequent in children. OBJECTIVE: To report 2 patients with Diamond-Blackfan anemia (DBA) who developed impaired renal function secondary to the administration of Deferasirox. CLINICAL CASES: Case 1. A 15-year-old adolescent diagnosed with DBA undergoing treatment with periodic transfusions and Deferasirox. During an acute gastroenteritis, she developed acute renal failure along with complex proximal tubu- lopathy. Case 2. A 5-year-old boy diagnosed with DBA receiving periodic transfusions and treatment with Deferasirox. He presented polyuria with laboratory abnormalities compatible with acute renal failure and proximal tubular dysfunction. In both cases, they were adequately hydrated and Deferasi rox was temporarily suspended, improving renal function. CONCLUSION: Based on these cases, close monitoring of renal and tubular function, as well as ferritin levels, is recommended in patients recei ving Deferasirox. In the presence of intercurrent processes, adequate hydration should be performed, and an early dose reduction or drug administration interruption should be considered in cases of kidney involvement.

When a transfusion in an emergency service is not really urgent: hyperhaemolysis syndrome in a child with sickle cell disease.

A 13-month-old boy with sickle cell disease (SCD) from Equatorial Guinea, who had recently arrived in Spain, presented with fever. He had suffered from malaria and had received a blood transfusion. Following physical examination and complementary tests, intravenous antibiotics and a red blood cell (RBC) transfusion were administered. Soon after a second transfusion 5 days later, the haemoglobin level fell below pretransfusion levels, together with reticulocytopenia, and haematuria-the so-called hyperhaemolysis syndrome-requiring intensive care and treatment with intravenous immunoglobulins and corticosteroids, with resolution of the complication. We want to emphasise the importance of suspecting this rare, though severe complication that can appear after any RBC transfusion especially in patients with SCD, as the clinical syndrome can simulate other more common complications of these patients and a further transfusion is contraindicated. There is no standardised treatment, but intravenous immunoglobulin and corticosteroids are usually effective.