Relapsing Acute Axonal Neuropathy in Hereditary Fructose Intolerance.

BACKGROUND: A severe neurological abnormality has not been previously described in individuals with hereditary fructose intolerance, which typically presents early in childhood with severe metabolic acidosis and hypoglycemia. PATIENT DESCRIPTION: We describe a boy who by age five years had required multiple admissions to the pediatric intensive care unit for an aggressive and atypical, relapsing and remitting neuropathy with features of acute motor axonal neuropathy (AMAN). It was later discovered that he also had undiagnosed hereditary fructose intolerance, and the severity and frequency of his neurological episodes diminished following an exclusion diet. His asymptomatic younger brother was diagnosed with hereditary fructose intolerance on screening. He is on a fructose-free diet and has not developed neurological symptoms. CONCLUSIONS: Ongoing low-level exposure to fructose prior to diagnosis may have contributed to our patient's neurological dysfunction. Early diagnosis and treatment may prevent neurological complications of hereditary fructose intolerance.

Non-invasive ventilation in paediatric critical care.

Non-invasive ventilation (NIV) is a well recognised and increasingly prevalent intervention in the paediatric critical care setting. In the acute setting NIV is used to provide respiratory support in a flexible manner that avoids a requirement for endotracheal intubation or tracheostomy, with the aim of avoiding the complications of invasive ventilation. This article will explore the physiological benefits, complications and epidemiology of the different modes of NIV including continuous positive airway pressure (CPAP), non-invasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen (HFNC). The currently available equipment and patient interfaces will be described, and the practical aspects of using NIV clinically will be explored. The current evidence for use of NIV in different clinical settings will be discussed, drawing on adult and neonatal as well as paediatric literature.

Expression of a single-chain human leukocyte antigen-DRA/DRB3*01:01 molecule and differential binding of a monoclonal antibody in the presence of specifically bound human platelet antigen-1a peptide.

BACKGROUND: Studies show that 1 in 1200 neonates have a low platelet (PLT) count due to alloimmunization against human PLT antigen (HPA)-1a (ß3 -L33). This mainly occurs in HPA-1a-negative mothers who are positive for the human leukocyte antigen (HLA)-DRB3*01:01 allele, but only about one-third of cases will mount an effective alloimmune response. The development of specific treatment modalities requires that the mechanisms driving the maternal alloimmune response against the fetal PLTs be further explored. An antibody reagent that has a different binding affinity to HLA-DRA/DRB3*01:01 with and without the ß3 -L33 peptide would be a valuable reagent to study peptide presentation on maternal antigen-presenting cells. STUDY DESIGN AND METHODS: To identify such antibodies, HLA-DRA/DRB3*01:01 was recombinantly expressed in Drosophila S2 cells. To delineate the epitope of interesting antibodies, seven mutant HLA-DRA/DRB3*01:01 molecules were generated by site-directed mutagenesis introducing naturally occurring amino acid changes encoded by DRB3*02 and DRB3*03 alleles. RESULTS: The murine monoclonal antibody (MoAb) DA2 showed robust binding by enzyme-linked immunosorbent assay to recombinant HLA-DRA/DRB3*01:01, but binding was reduced in the presence of ß3 -L33 peptide. The binding affinity of DA2 to the mutant HLA-DRA/DRB3*0101 in which serine at Position 60 of the ß1-chain was replaced by tyrosine was greatly enhanced. Interestingly the binding of DA2 to the mutant was not reduced by the presence of ß3 -L33 peptide. CONCLUSION: The results of this study generate a molecular model of the interaction of the HLA-DRA/DRB3*01:01 molecule with MoAb DA2. This will inform functional studies with the recombinant Class II molecules.

Management of acquired coagulopathy in acute paediatrics.

Acquired coagulopathy is a relatively uncommon occurrence in acute paediatrics but when it occurs is usually associated with significant underlying pathology and often with critical illness. It can be caused by a number of disease processes but infection, blood loss, iatrogenic causes and liver dysfunction are among the commonest. The blood coagulation cascade is complex and intersects with many other physiological pathways. It is also subject to developmental changes, and 'normal' coagulation and haemostasis change considerably during early life. The diagnosis of abnormal coagulation and when treatment should be initiated is influenced both by age and developmental status and limited by the range of tests routinely available to clinicians. Treatment has predominantly involved transfusion of plasma products (usually fresh frozen plasma and cryoprecipitate) but a number of pharmaceutical and human-derived options are now available. Although plasma products are less frequently transfused than red cells or platelets, their use continues to increase and has not followed the reducing usage of other blood components. This article discusses the aetiology of coagulopathy, describes the commonly available diagnostic tests and outlines the evidence available to guide paediatricians when treating acutely ill children with acquired coagulopathy.

A HaemAtlas: characterizing gene expression in differentiated human blood cells.

Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.

Severe cardiovascular and thromboembolic consequences of pneumococcal infection in a child.

We present an unusually severe case of pneumococcal infection in an immunocompetent child who progressed from pneumonia to empyema, pericarditis with cardiac tamponade, and severe venous thromboembolism leading to life-threatening pulmonary embolus.

Age dependence of in vitro survival of meningococci in whole blood during childhood.

OBJECTIVES: To determine the association between the ability of a different strains of meningococci to survive in whole blood and the age of the donor. METHODS: A panel of serogroup B and a serogroup C strain of Neisseria meningitidis was tested in an ex vivo whole blood model. Blood from 81 healthy children and 20 adults and from children during convalescence from serogroup B (55 patients) or serogroup C (43 patients) meningococcal infection was assessed. RESULTS: Age-dependent acquisition of whole blood killing of serogroup B and C bacterial isolates was demonstrated in healthy children with an inverse relationship to the reported incidence of disease. After infection with serogroup B or C meningococci, evidence of whole blood killing of the bacteria was found even in blood from children <2 years of age, the survival of a serogroup B strain, MC58, being reduced compared with that in healthy children (median, 64% compared with 194.5% survival at 90 min). In both affected children and controls, there was a significant correlation between whole blood killing of strain MC58 and of other serogroup B and C meningococci. CONCLUSIONS: The whole blood model measures both humoral and cellular mechanisms responsible for the bactericidal activity of blood. The model was first described 80 years ago, but this is the first description of its age dependency. Acquisition of bactericidal activity was more rapid in children infected and is directed at various strains of meningococci, indicating the presence of a cross-reactive antigen(s).