Pediatric Antiphospholipid Syndrome: Clinical and Immunologic Features of 121 Patients in an International Registry

OBJECTIVES. The purpose of this study was to obtain data on the association of antiphospholipid antibodies with clinical manifestations in childhood and to enable future studies to determine the impact of treatment and long-term outcome of pediatric antiphospholipid syndrome. PATIENTS AND METHODS. A European registry extended internationally of pediatric patients with antiphospholipid syndrome was established as a collaborative project of the European Antiphospholipid Antibodies Forum and Lupus Working Group of the Pediatric Rheumatology European Society. To be eligible for enrollment the patient must meet the preliminary criteria for the classification of pediatric antiphospholipid syndrome and the onset of antiphospholipid syndrome must have occurred before the patient`s 18th birthday. RESULTS. As of December 1, 2007, there were 121 confirmed antiphospholipid syndrome cases registered from 14 countries. Fifty-six patients were male, and 65 were female, with a mean age at the onset of antiphospholipid syndrome of 10.7 years. Sixty (49.5%) patients had underlying autoimmune disease. Venous thrombosis occurred in 72 (60%), arterial thrombosis in 39 (32%), small-vessel thrombosis in 7 (6%), and mixed arterial and venous thrombosis in 3 (2%). Associated nonthrombotic clinical manifestations included hematologic manifestations (38%), skin disorders (18%), and nonthrombotic neurologic manifestations (16%). Laboratory investigations revealed positive anticardiolipin antibodies in 81% of the patients, anti-beta(2)-glycoprotein I antibodies in 67%, and lupus anticoagulant in 72%. Comparisons between different subgroups revealed that patients with primary antiphospholipid syndrome were younger and had a higher frequency of arterial thrombotic events, whereas patients with antiphospholipid syndrome associated with underlying autoimmune disease were older and had a higher frequency of venous thrombotic events associated with hematologic and skin manifestations. CONCLUSIONS. Clinical and laboratory characterization of patients with pediatric antiphospholipid syndrome implies some important differences between antiphospholipid syndrome in pediatric and adult populations. Comparisons between children with primary antiphospholipid syndrome and antiphospholipid syndrome associated with autoimmune disease have revealed certain differences that suggest 2 distinct subgroups. Pediatrics 2008; 122: e1100-e1107

Carcinoid syndrome - Case report

Carcinoid tumors are rare neoplasms with, an estimated incidence of I to 2 cases per 100, 000 inhabitants. The malignant carcinoid syndrome, characterized by flushing, diarrhea, abdominal pain and, less frequently, pellagra, bronchospasm and valvular disease, occurs in less than 10% of patients. Nevertheless, in advanced stages of the disease, the incidence is about 40 to 50%. Retrospective studies and descriptive case series have shown that cutaneous involvement is relatively common but has rarely been reported. We present a case of carcinoid syndrome diagnosed with basis on skin findings on clinical examination.

Disseminated blue naevus and malignant blue naevus associated with excessive aromatase syndrome

We report a case of a 17-year-old boy who had a giant congenital blue naevus with multiple satellite pigmented lesions. Later the patient developed melanoma arising in the pre-existing lesion. He also had gynaecomastia and was diagnosed as having aromatase excess syndrome. To our knowledge, the association of these two rare conditions has not been previously reported. Further studies should be performed to investigate this unusual combination, which may have a genetic, endocrine or local cutaneous link leading to its occurrence.

Impact of metabolic syndrome on the outcome of patients with stable coronary artery disease: 2-year follow-up of the MASS II study

Objective We characterized the impact of the metabolic syndrome (MetS) and its components on cardiovascular adverse events in patients with symptomatic chronic multivessel coronary artery disease, which have been followed prospectively for 2 years. Methods Patients enrolled in the MASS II study were evaluated for each component of the MetS, as well as the full syndrome. Results The criteria for MetS were fulfilled in 52% of patients. The presence of MetS (P < 0.05), glucose intolerance (P=0.007), and diabetes (P=0.04) was associated with an increased mortality in our studied population. Moreover, despite a clear tendency for each of its components to increase the mortality risk, only the presence of the MetS significantly increased the risk of mortality among nondiabetic study participants in a multivariate model (P=0.03, relative risk 3.5, 95% confidence interval 1.1-6). Finally, MetS was still associated with increased mortality even after adjustment for diabetes status. These results indicate a strong and consistent relationship of the MetS with mortality in patients with stable coronary artery disease. Conclusion Although glucose homeostasis seems to be the major force driving the increased risk of MetS, the operational diagnosis of MetS still has information for stratifying patients when diabetes information is taken into account.

New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome

We report the identification of a novel mutation at a highly conserved residue within the N-terminal region of spermine synthase (SMS) in a second family with Snyder-Robinson X-linked mental retardation syndrome ( OMIM 309583). This missense mutation, p.G56S, greatly reduces SMS activity and leads to severe epilepsy and cognitive impairment. Our findings contribute to a better delineation and expansion of the clinical spectrum of Snyder-Robinson syndrome, support the important role of the N-terminus in the function of the SMS protein, and provide further evidence for the importance of SMS activity in the development of intellectual processing and other aspects of human development.

Cardiovascular Risk and Clinical Factors in Athletes: 10 Years of Evaluation

DE MATOS, L. D. N. J., N. D. A. O. CALDEIRA, P. D. S. PERLINGEIRO, I. L. G. DOS SANTOS, C. E. NEGRAO and L. F. AZEVEDO. Cardiovascular Risk and Clinical Factors in Athletes: 10 Years of Evaluation. Med. Sci. Sports Exerc., Vol. 43, No. 6, pp. 943-950, 2011. Purpose: Preparticipation screening in athletes is a very current but controversial theme. Part of this controversy is due to the cost benefit, especially when the screening is merely used as a prevention of sudden cardiac death caused by rare and hereditary diseases. The purpose of this study was to describe the prevalence of preexisting diseases, cardiovascular risk factor for cardiovascular diseases development, and hematological profile in a population of amateur and professional athletes. Methods: Data of 623 athletes (529 men and 94 women), aged 13-77 yr, were analyzed to detect preexisting diseases. The variables total cholesterol, LDL, HDL, triglycerides, fasting glucose, body mass index, hemoglobin, hematocrit, and ferritin were analyzed in two groups according to age, that is, younger and older 35 yr old, and their prevalence (%) and distribution in quartiles were presented. chi(2) test and Pearson product-moment correlation coefficients between variables were applied, and P < 0.05 was adopted for significance. Results: Hypertension was the most prevalent preexisting diseases, although the data showed low prevalence of cardiomyopathy. Cardiovascular risk factors were prevalent in both genders. There were positive correlations between cardiovascular risk factors and age and between body mass index and lipid levels in male athletes. Also, there was a high prevalence of low ferritin levels for women, with positive correlation between the levels of hemoglobin and ferritin. Conclusions: In the present study, hypertension was the most prevalent diagnosed disease, and cardiovascular risk factors showed important prevalence, especially in athletes older than 35 yr. Although physical training represents a cardioprotective factor to the onset of cardiovascular disease, it does not exclude the prevalence of risk factors and diseases in athletes.

Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide

Lymphocyte and neutrophil death induced by exercise and the role of hydrolyzed whey protein enriched with glutamine dipeptide (Gln) supplementation was investigated. Nine triathletes performed two exhaustive exercise trials with a 1-week interval in a randomized, double blind, crossover protocol. Thirty minutes before treadmill exhaustive exercise at variable speeds in an inclination of 1% the subjects ingested 50 g of maltodextrin (placebo) or 50 g of maltodextrin plus 4 tablets of 700 mg of hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide dissolved in 250 mL water. Cell viability, DNA fragmentation, mitochondrial transmembrane potential and production of reactive oxygen species (ROS) were determined in lymphocytes and neutrophils. Exhaustive exercise decreased viable lymphocytes but had no effect on neutrophils. A 2.2-fold increase in the proportion of lymphocytes and neutrophils with depolarized mitochondria was observed after exhaustive exercise. Supplementation of maltodextrin plus Gln (MGln) prevented the loss of lymphocyte membrane integrity and the mitochondrial membrane depolarization induced by exercise. Exercise caused an increase in ROS production by neutrophils, whereas supplementation of MGln had no additional effect. MGln supplementation partially prevented lymphocyte apoptosis induced by exhaustive exercise possibly by a protective effect on mitochondrial function.

Disorders of apoptosis: Mechanisms for autoimmunity in primary immunodeficiency diseases

A number of primary immunodeficiency diseases represent a paradox of immunodeficiency and autoimmunity. In this minireview, we present basic concepts of apoptosis and disorder of apoptosis as one of the mechanisms to explain such a paradox between immunodeficiency and autoimmunity, which is exemplified by autoimmune lympho-proliferative syndrome (ALPS).

Alagille syndrome and nephroblastoma: Unusual coincidence of two rare disorders

Alagille syndrome is a rare developmental disorder combining bile duct paucity, congenital cardiopathy, facial dysmorphy, vertebrae defects, and ocular abnormalities; and frequent renal abnormalities. It does not usually predispose to malignancies. Nephroblastoma has been observed in many developmental disorders, but never in Alagille syndrome. We report two original cases of nephroblastoma associated to Alagille syndrome. We identified a new V136G JAG1 missense mutation in one patient and a constitutional deletion of 20p12 in the other. In one nephroblastoma an additional somatic 1p36 deletion was present. The link between Alagille syndrome, JAG1 alterations and nephroblastoma is discussed.

Two cases of Kallmann syndrome associated with empty sella

Kallmann syndrome (KS) is a developmental disease characterized by the association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We report an unusual presentation of two females with KS and empty sella. These females, aged at 20 and 29-year-old, presented primary amenorrhea with prepubertal estradiol and low gonadotropin levels. No other significant clinical signs were observed. Empty sella was observed on MRI in both cases. Sequencing of FGFR1 gene, recently implicated in autosomal form of KS, was performed and one splicing mutation (IVS14 + 1G > A) was identified in one patient.

Three Different Mechanisms of Death An Unusual Form of a Child Murder by Asphyxia

We report a very unusual case of murder of a 4-year-old male white child who died of asphyxiation. Asphyxia occurred due to 3 factors: manual strangulation, hyperextension of the neck, and atlantoaxial subluxation. The offenses were carried out by a single assailant (the stepfather of the child) who strangled the child with his right hand, using his left hand to pull the hair of the child, forcing the head back and causing hyperextension of the neck, thereby dislocating the first and second cervical vertebrae.

Moving ear syndrome: The role of botulinum toxin

We report a 30-year-old man with moving ear syndrome caused by focal myoclonic jerks of the right temporal muscle. This focal myoclonus would disappear while the patient was sleeping, swallowing, or speaking. He was treated with botulinum toxin type A with a favorable outcome. Previous reports of this condition and possible therapeutic approaches are discussed. (c) 2007 Movement Disorder Society.

Ultrasound features of carpal tunnel syndrome: a prospective case-control study

Purpose The purpose of the study was to examine the most adequate cut-off point for median nerve cross-sectional area and additional ultrasound features supporting the diagnosis of carpal tunnel syndrome (CTS). Material and methods Forty wrists from 31 CTS patients and 63 wrists from 37 asymptomatic volunteers were evaluated by ultrasound. All patients were women. The mean age was 49.1 years (range: 29-78) in the symptomatic and 45.1 years (range 24-82) in the asymptomatic group. Median nerve cross-sectional area was obtained using direct (DT) and indirect (IT) techniques. Median nerve echogenicity, mobility, flexor retinaculum measurement and the anteroposterior (AP) carpal tunnel distance were assessed. This study was IRB-approved and all patients gave informed consent prior to examination. Results In CTS the median nerve cross-sectional area was increased compared with the control group. Median nerve cross-sectional area of 10 mm(2) (DT) and 9 mm(2) (IT) had high sensitivity (85% and 88.5%, respectively), specificity (92.1% and 82.5%) and accuracy (89.3% and 82.5%) in the diagnosis of CTS. CTS patients had an increased carpal tunnel AP diameter, flexor retinaculum thickening, reduced median nerve mobility and decreased median nerve echogenicity. Conclusion Ultrasound assists in the diagnosis of CTS using the median nerve diameter cut-off point of 10 mm(2) (DT) and 9 mm(2) (IT) and several additional findings.

A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings

Background: GH insensitivity (GHI) syndrome caused by STAT5B mutations was recently reported, and it is characterized by extreme short stature and immune dysfunction. Treatment with recombinant human IGF1 (rhIGF1) is approved for patients with GHI, but the growth response to this therapy in patients with STAT5B mutations has not been reported. Objectives: To report the clinical features, molecular findings, and the short-term growth response to rhIGF1 therapy in patients with STAT5B mutation. Subjects and methods: Hormonal and immunological evaluations were performed in two male siblings with GHI associated with atopic eczema, interstitial lung disease, and thrombocytopenic purpura. STAT5B genes were directly sequenced. The younger sibling was treated with rhIGF1 at a dose of 110 mu g/kg BID. Results: Both siblings had laboratory findings compatible with GHI associated with hyperprolactinemia. Lymphopenia and reduced number of natural killer cells without immunoglobulin abnormalities were observed. STAT5B sequence revealed a homozygous frameshift mutation (p.L142fsX161) in both siblings. The younger sibling (9.9 years of age) was treated with rhIGF1 at appropriate dosage, and he did not present any significant change in his growth velocity (from 2.3 to 3.0 cm/year after 1.5 years of therapy). The presence of a chronic illness could possibly be responsible for the poor result of rhIGF1 treatment. Further studies in patients with STAT5B defects are necessary to define the response to rhIGF1 treatment in this disorder. Conclusion: GHI associated with immune dysfunction, especially interstitial lung disease, and hyperprolactinemia is strongly suggestive of a mutation in STAT5B in both sexes.