Individual variation in levels of haptoglobin-related protein in children from Gabon

Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

Receptor protein tyrosine phosphatase alpha activates Src-family kinases and controls integrin-mediated responses in fibroblasts.

AbstractBackground: Fyn and c-Src are two of the most widely expressed Src-family kinases. Both are strongly implicated in the control of cytoskeletal organization and in the generation of integrin-dependent signalling responses in fibroblasts. These proteins are representative of a large family of tyrosine kinases, the activity of which is tightly controlled by inhibitory phosphorylation of a carboxy-terminal tyrosine residue (Tyr527 in chicken c-Src); this phosphorylation induces the kinases to form an inactive conformation. Whereas the identity of such inhibitory Tyr527 kinases has been well established, no corresponding phosphatases have been identified that, under physiological conditions, function as positive regulators of c-Src and Fyn in fibroblasts.Results: Receptor protein tyrosine phosphatase α (RPTPα) was inactivated by homologous recombination. Fibroblasts derived from these RPTPα−/− mice had impaired tyrosine kinase activity of both c-Src and Fyn, and this was accompanied by a concomitant increase in c-Src Tyr527 phosphorylation. RPTPα−/− fibroblasts also showed a reduction in the rate of spreading on fibronectin substrates, a trait that is a phenocopy of the effect of inactivation of the c-src gene. In response to adhesion on a fibronectin substrate, RPTPα−/− fibroblasts also exhibited characteristic deficiencies in integrin-mediated signalling responses, such as decreased tyrosine phosphorylation of the c-Src substrates Fak and p 130cas, and reduced activation of extracellular signal regulated (Erk) MAP kinases.Conclusions: These observations demonstrate that RPTPα functions as a physiological upstream activator of Src-family kinases in fibroblasts and establish this tyrosine phosphatase as a newly identified regulator of integrin signalling

Managing pulmonary embolism secondary to suppurative deep vein thrombophlebitis due to community-acquired Staphylococcus aureus in a resource-poor setting

Deep vein thrombosis and pulmonary thromboembolism are rare and life threatening emergencies in children. We report an 11-year old female who presented with acute complaints of high grade fever, pain in the left thigh and inability to walk and breathlessness since 6 days. On physical examination, there was a diffuse tender swelling of the left thigh, tachypnea, tachycardia with hyperdynamic precordium and bilateral basal crepitations. Ultrasonography and venous doppler of lower limbs showed mild effusion of left hip joint and thrombus in the left common femoral vein and left external iliac vein suggesting a diagnosis of septic arthritis with thrombophlebitis. The tachypnea and tachycardia which was out of proportion to fever and crepitations on auscultation prompted suspicion of an embolic phenomenon. Radiograph of the chest revealed multiple wedge shaped opacities in the right middle zone and lower zone suggestive of pulmonary embolism and left lower zone consolidation. For corroboration, computed tomography pulmonary angiography and computed tomography of abdomen was performed which showed pulmonary thromboembolism and deep venous thrombosis extending up to infrarenal inferior vena cava. On further workup, magnetic resonance imaging of hips showed left femoral osteomyelitis and multiple intramuscular abscesses in the muscles around the hip joint. Blood culture grew methicillin resistant Staphylococcus aureus. Antibiotics were changed according to culture sensitivity and there was a dramatic response. After four weeks of anticoagulation and antibiotics the child became asymptomatic and thrombus resolved. Thus, it is crucial to consider methicillin resistant Staphylococcus aureus infection as an important infection when we encounter such a clinical scenario. This case report highlights an unusual and potentially life threatening presentation of a virulent strain of a common pathogen, which when diagnosed was completely amenable to treatment

Childhood cerebral X-linked adrenoleukodystrophy with atypical neuroimaging abnormalities and a novel mutation

Childhood cerebral X-linked adrenoleukodystrophy (XALD) typically manifests with symptoms of adrenocortical insufficiency and a variety of neurocognitive and behavioral abnormalities. A major diagnostic clue is the characteristic neuroinflammatory parieto-occipital white matter lesions on magnetic resonance imaging. This study reports a 5-year 10-month old boy presenting with generalized skin hyperpigmentation since 3 years of age. Over the past 9 months, he had developed right-sided hemiparesis and speech and behavioral abnormalities, which had progressed over 5 months to bilateral hemiparesis. Retrospective analyses of serial brain magnetic resonance images revealed an unusual pattern of lesions involving the internal capsules, corticospinal tracts in the midbrain and brainstem, and cerebellar white matter. The clinical diagnosis of childhood cerebral adrenoleukodystrophy was confirmed by elevated basal levels of adrenocorticotropin hormone and plasma very long chain fatty acid levels. Additionally, sequencing of the ABCD1 gene revealed a novel mutation. The only specific palliative therapy that could be offered after diagnosis was dietary intervention. The patient died within 16 months of onset of neurological symptoms. Awareness that childhood cerebral XALD can present with atypical neuroimaging patterns early in its course may aid diagnosis at a stage when definitive treatment can be attempted and timely genetic counseling be offered to the family

Porphyrias: Uncommon disorders masquerading as common childhood diseases

Porphyrias are a rare group of inborn errors of metabolism due to defects in the heme biosynthetic pathway. The biochemical hallmark is the overproduction of porphyrin precursors and porphyrin species. Afflicted patients present with a myriad of symptoms causing a diagnostic odyssey. Symptoms often overlap with those of common diseases and may be overlooked unless there is heightened clinical suspicion. We are reporting clinical features and diagnostic challenges in four pediatric patients having variegate porphyria, congenital erythropoietic porphyria, acute intermittent porphyria, and erythropoietic protoporphyria (EPP), who presented with diverse multisystem manifestations. This case series illustrates a logical analysis of symptoms and judicious selection of investigations and the role of genotyping in successfully diagnosing porphyrias

Incomplete Kawasaki disease with recurrent skin peeling: a case report with the review of literature.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that has largely replaced rheumatic heart disease as a cause of acquired heart disease in children of many developed countries. We report a case of incomplete KD in a five-year-old girl. The diagnosis of incomplete KD was made after exclusion of conditions with similar presentation. She was treated with intravenous immunoglobulin following which she made an uneventful recovery but demonstrated thrombocytosis in the second week of convalescence. During the six-month follow up period, she had two episodes of recurrent skin peeling a phenomenon, which is recently reported with KD but not with atypical or incomplete KD. It is important for the treating physicians to become aware of the incomplete KD as prompt diagnosis and early treatment of these patients with intravenous immunoglobulin is vital for the prevention of lethal coronary complications. Physicians need to have a "high index of suspicion" for KD and even, higher for IKD

Ovarian dysgenesis with balanced autosomal translocation.

Autosomal translocations are rare in the patients with ovarian dysgenesis. An 18-year-old female who presented with primary amenorrhoea had hypergonadotropic hypogonadism and streak ovaries with hypoplastic uterus. Karyotype analysis revealed a balanced autosomal translocation involving chromosomes 1 and 11. The probable role of autosomal translocations in ovarian dysgenesis has been discussed

Rare disease heralded by pulmonary manifestations: Avoiding pitfalls of an “asthma” label

Pulmonary manifestations are seldom recognized as symptoms of storage disorders. The report describes the diagnostic journey in a 30-month-old male infant, born of a third-degree consanguineous marriage referred to our institute as severe persistent asthma. History revealed that the child had progressively worsening breathlessness and persistent dry cough not associated with fever but accompanied by weight loss. On physical examination, there was growth failure, respiratory distress, clubbing, hepatosplenomegaly, and occasional rhonchi. Blood gas revealed hypoxemia which improved with oxygen administration. Plain X-rays and high-resolution computed tomography of the chest showed perihilar alveolar infiltrates and patchy consolidation. The clinicoradiological features did not support a diagnosis of asthma but favored interstitial lung disease (ILD). Bronchoalveolar lavage was performed as a first-tier investigation. It showed periodic acid–Schiff-negative foamy macrophages. The clues of consanguinity, visceromegaly, ILD, and foamy macrophages in the bronchoalveolar fluid prompted consideration of lysosomal storage disorders as the likely etiology. Gaucher disease and Niemann–Pick disease A/B were ruled out by enzyme estimation. Niemann–Pick disease type C was suspected and confirmed by detecting a homozygous mutation in the NPC2 gene. This case serves to caution physicians against labeling breathlessness in every toddler as asthma. It emphasizes the importance of searching for tell-tale signs such as clubbing and extrapulmonary clues which point to a systemic disease such as lysosomal storage disorders as a primary etiology of chronic respiratory symptoms