Hemolytic uremic syndrome with Mycoplasma pneumoniae infection and membrane cofactor protein mutation ­ case report.

Thrombotic microangiopathies (TMA) are rare life-threatening diseases of various etiologies, making the identification of the specific forms and appropriate treatment difficult. The aim of this work is to present the history of a patient with atypical hemolytic uremic syndrome (aHUS) that developed in the context of Mycoplasma pneumoniae infection. Case presentation: A 5 - year old, Caucasian, previously healthy girl presented with symptoms of HUS, without preceding diarrhoea and with ongoing upper respiratory tract infection. ADAMTS13 deficiency and presence of Shiga-like toxin producing E. coli (STEC) was excluded, and the diagnosis of aHUS verified. She required peritoneal dialysis for 4 days and fresh frozen plasma (FFP) treatment was started with good clinical response. Serological investigation for Mycoplasma pneumoniae was positive (IgM) leading to the initiation of clarithromycin therapy. The complement profile (classical pathway activity, C3 and C4 serum levels were slightly decreased, no signs of alternative pathway dysregulation) was indicative for classical pathway activation and consumption. The genetic screening revealed a novel non-synonymous variation in the CD46 (MCP) gene in heterozygous form that causes a proline to leucine change at codon 155 of the MCP (P155L). The CD46 P155L variation was associated in the samples of the patient and family members with decreased MCP protein expression on the surface of granulocytes. In addition to the P155L mutation, multiple frequent aHUS risk variations were also identified. Conclusion: The diagnosis of aHUS is challenging and is based mainly on the exclusion of ADAMTS13 deficient thrombotic thrombocytopenic purpura (TTP) and typical HUS caused by STEC. Our patient had single-episodic HUS in the context of upper-airway infection, and finally a functionally relevant CD46 (MCP) mutation was identified. The complexity of aHUS, and the importance of the requirement for full differential diagnostic workup of all HUS cases is further highlighted by the current case history.

Application of a Reactive Agility Training Program Using Light-Based Stimuli to Enhance the Physical and Cognitive Performance of Car Racing Drivers: A Randomized Controlled Trial.

BACKGROUND: There is a need to develop strategies that could contribute to the physical and mental preparation of motorsport athletes. A common method used by experienced motorsport athlete physical trainers is flashing light devices to train or assess reactive agility, despite limited evidence. Therefore, in the present study, we determined the effects of a 6-week reactive agility training program using light-based stimuli on the physiological and cognitive abilities of car racing drivers. MATERIALS AND METHODS: The CONSORT guidelines for randomized controlled trial were used. In a single-blinded randomized controlled trial, 24 car racing drivers (EXP, n = 12; CON, n = 12) performed a comprehensive battery of cognitive tests marketed specifically at motorsport athletes from Vienna test system (VTS) at rest or during moderate intensity exercise on a bicycle. Physiological abilities were determined via a maximal incremental cardio-respiratory treadmill test. Baseline and post-intervention tests were performed on three consecutive days. Participants in EXP underwent a 6-week intervention consisting of 60-min training sessions twice a week using the Witty SEM light stimulus. RESULTS: Participants in EXP but not in CON performed some of the VTS cognitive tasks with higher accuracy and/or shorter reaction time after the intervention at rest and during exercise. Car racing drivers performed the STROOP word-reading condition more accurately when the task was performed during the exercise vs. rest, regardless of group. In addition, the intervention induced beneficial changes in peak heart rate (HR), HR at gas exchange threshold, ventilation, and relative maximal oxygen consumption (rVO2 max). In contrast, body mass and fat mass increased, while peak HR and rVO2 max decreased in CON. Finally, participants in EXP improved their reactive agility performance and reaction time throughout the training program. CONCLUSION: Overall, the reactive agility training program using light-based stimuli appeared to be efficient to induce beneficial effects on some physiological and cognitive performance measures; therefore, it may have the potential to contribute to car racing drivers' physical and mental performance.

Genetic analysis and functional characterization of novel mutations in a series of patients with atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by dysregulation of the complement alternative pathway, and associated with mutations in genes of complement components and regulators. In the recent years several studies have been published describing these mutations, however, no data is available from the Central and Eastern European region. In this study we present a detailed genetic analysis of our 30 patients, hospitalized with the diagnosis of aHUS in the past 7 years. We analyzed the genetic variants of genes CFH, CFI, CD46, THBD, CFB and C3; furthermore the possible effect of mutations that may alter the function or level of factor H protein was also investigated. We identified 27 (12 novel and 15 previously described) potentially disease-causing mutations in the candidate genes in 23 patients. Genetic analysis of family members revealed that in most cases the disease develops in individuals with multiple genetic risk factors, which may explain the low penetrance of the mutations. Here we showed that two novel mutations (p.W198R, p.P1161T) and a previously reported one (p.R1215Q) in CFH caused impaired regulation as indicated by increased lysis in hemolytic test, while four CFH mutations (p.V609D, p.S722X, p.T1216del and p.C448Y) were associated with decreased factor H protein level in serum as determined by allele-specific immunoassay. These results further point to the necessity of complete genetic workup of patients with aHUS and to the importance of functional characterization of novel variations.