Cross-sectional observational study of 208 patients with non-classical urea cycle disorders

Urea cycle disorders (UCDs) are inherited disorders of ammonia detoxification often regarded as mainly of relevance to pediatricians. Based on an increasing number of case studies it has become obvious that a significant number of UCD patients are affected by their disease in a non-classical way: presenting outside the newborn period, following a mild course, presenting with unusual clinical features, or asymptomatic patients with only biochemical signs of a UCD. These patients are surviving into adolescence and adulthood, rendering this group of diseases clinically relevant to adult physicians as well as pediatricians. In preparation for an international workshop we collected data on all patients with non-classical UCDs treated by the participants in 20 European metabolic centres. Information was collected on a cohort of 208 patients 50% of which were ≥ 16 years old. The largest subgroup (121 patients) had X-linked ornithine transcarbamylase deficiency (OTCD) of whom 83 were female and 29% of these were asymptomatic. In index patients, there was a mean delay from first symptoms to diagnosis of 1.6 years. Cognitive impairment was present in 36% of all patients including female OTCD patients (in 31%) and those 41 patients identified presymptomatically following positive newborn screening (in 12%). In conclusion, UCD patients with non-classical clinical presentations require the interest and care of adult physicians and have a high risk of neurological complications. To improve the outcome of UCDs, a greater awareness by health professionals of the importance of hyperammonemia and UCDs, and ultimately avoidance of the still long delay to correctly diagnose the patients, is crucial

Solar wind protons forming partial ring distributions at comet 67P

We present partial ring distributions of solar wind protons observed by the Rosetta spacecraft at comet 67P/Churyumov-Gerasimenko. The formation of ring distributions is usually associated with high activity comets, where the spatial scales are larger than multiple ion gyroradii. Our observations are made at a low-activity comet at a heliocentric distance of 2.8 AU on 19 April 2016, and the partial rings occur at a spatial scale comparable to the ion gyroradius. We use a new visualization method to simultaneously show the angular distribution of median energy and differential flux. A fitting procedure extracts the bulk speed of the solar wind protons, separated into components parallel and perpendicular to the gyration plane, as well as the gyration velocity. The results are compared with models and put into context of the global comet environment. We find that the formation mechanism of these partial rings of solar wind protons is entirely different from the well-known partial rings of cometary pickup ions at high-activity comets. A density enhancement layer of solar wind protons around the comet is a focal point for proton trajectories originating from different regions of the upstream solar wind. If the spacecraft location coincides with this density enhancement layer, the different trajectories are observed as an energy-angle dispersion and manifest as partial rings in velocity space

Upstream solar wind speed at comet 67P : reconstruction method, model comparison, and results

Context: Rosetta followed comet 67P at heliocentric distances from 1.25 to 3.6 au. The solar wind was observed for much of this time, but was significantly deflected and to some extent slowed down by the interaction with the coma. Aims: We use the different changes in the speed of H+ and He2+ when they interact with the coma to estimate the upstream speed of the solar wind. The different changes in the speed are due to the different mass per charge of the particles, while the electric force per charge due to the interaction is the same. A major assumption is that the speeds of H+ and He2+ were the same in the upstream region. This is investigated. Methods: We derived a method for reconstructing the upstream solar wind from H+ and He2+ observations. The method is based on the assumption that the interaction of the comet with the solar wind can be described by an electric potential that is the same for both H+ and He2+. This is compared to estimates from the Tao model and to OMNI and Mars Express data that we propagated to the observation point. Results: The reconstruction agrees well with the Tao model for most of the observations, in particular for the statistical distribution of the solar wind speed. The electrostatic potential relative to the upstream solar wind is derived and shows values from a few dozen volts at large heliocentric distances to about 1 kV during solar events and close to perihelion. The reconstructed values of the solar wind for periods of high electrostatic potential also agree well with propagated observations and model results. Conclusions: The reconstructed upstream solar wind speed during the Rosetta mission agrees well with the Tao model. The Tao model captures some slowing down of high-speed streams as compared to observations at Earth or Mars. At low solar wind speeds, below 400 km s-1, the agreement is better between our reconstruction and Mars observations than with the Tao model. The magnitude of the reconstructed electrostatic potential is a good measure of the slowing-down of the solar wind at the observation point

The natural history of classic galactosemia : Lessons from the GalNet registry

Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Methods: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Results: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. Conclusion: This study describes the natural history of classic galactosemia based on the hitherto largest data set