Glucose-6-phosphatase deficiency

Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed by G6PC (GSDIa) or SLC37A4 (GSDIb) gene analysis, and the indications of liver biopsy to measure G6P activity are getting rarer and rarer. Differential diagnoses include the other GSDs, in particular type III (see this term). However, in GSDIII, glycemia and lactacidemia are high after a meal and low after a fast period (often with a later occurrence than that of type I). Primary liver tumors and Pepper syndrome (hepatic metastases of neuroblastoma) may be evoked but are easily ruled out through clinical and ultrasound data. Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villous cells. Pre-implantatory genetic diagnosis may also be discussed. Genetic counseling should be offered to patients and their families. The dietary treatment aims at avoiding hypoglycemia (frequent meals, nocturnal enteral feeding through a nasogastric tube, and later oral addition of uncooked starch) and acidosis (restricted fructose and galactose intake). Liver transplantation, performed on the basis of poor metabolic control and/or hepatocarcinoma, corrects hypoglycemia, but renal involvement may continue to progress and neutropenia is not always corrected in type Ib. Kidney transplantation can be performed in case of severe renal insufficiency. Combined liver-kidney grafts have been performed in a few cases. Prognosis is usually good: late hepatic and renal complications may occur, however, with adapted management, patients have almost normal life span

Glucose-6-phosphatase deficiency

Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed by G6PC (GSDIa) or SLC37A4 (GSDIb) gene analysis, and the indications of liver biopsy to measure G6P activity are getting rarer and rarer. Differential diagnoses include the other GSDs, in particular type III (see this term). However, in GSDIII, glycemia and lactacidemia are high after a meal and low after a fast period (often with a later occurrence than that of type I). Primary liver tumors and Pepper syndrome (hepatic metastases of neuroblastoma) may be evoked but are easily ruled out through clinical and ultrasound data. Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villous cells. Pre-implantatory genetic diagnosis may also be discussed. Genetic counseling should be offered to patients and their families. The dietary treatment aims at avoiding hypoglycemia (frequent meals, nocturnal enteral feeding through a nasogastric tube, and later oral addition of uncooked starch) and acidosis (restricted fructose and galactose intake). Liver transplantation, performed on the basis of poor metabolic control and/or hepatocarcinoma, corrects hypoglycemia, but renal involvement may continue to progress and neutropenia is not always corrected in type Ib. Kidney transplantation can be performed in case of severe renal insufficiency. Combined liver-kidney grafts have been performed in a few cases. Prognosis is usually good: late hepatic and renal complications may occur, however, with adapted management, patients have almost normal life span

First direct detection of an exoplanet by optical interferometry; Astrometry and K-band spectroscopy of HR8799 e

To date, infrared interferometry at best achieved contrast ratios of a few times $10^{-4}$ on bright targets. GRAVITY, with its dual-field mode, is now capable of high contrast observations, enabling the direct observation of exoplanets. We demonstrate the technique on HR8799, a young planetary system composed of four known giant exoplanets. We used the GRAVITY fringe tracker to lock the fringes on the central star, and integrated off-axis on the HR8799e planet situated at 390 mas from the star. Data reduction included post-processing to remove the flux leaking from the central star and to extract the coherent flux of the planet. The inferred K band spectrum of the planet has a spectral resolution of 500. We also derive the astrometric position of the planet relative to the star with a precision on the order of 100$\,\mu$as. The GRAVITY astrometric measurement disfavors perfectly coplanar stable orbital solutions. A small adjustment of a few degrees to the orbital inclination of HR 8799 e can resolve the tension, implying that the orbits are close to, but not strictly coplanar. The spectrum, with a signal-to-noise ratio of $\approx 5$ per spectral channel, is compatible with a late-type L brown dwarf. Using Exo-REM synthetic spectra, we derive a temperature of $1150\pm50$\,K and a surface gravity of $10^{4.3\pm0.3}\,$cm/s$^{2}$. This corresponds to a radius of $1.17^{+0.13}_{-0.11}\,R_{\rm Jup}$ and a mass of $10^{+7}_{-4}\,M_{\rm Jup}$, which is an independent confirmation of mass estimates from evolutionary models. Our results demonstrate the power of interferometry for the direct detection and spectroscopic study of exoplanets at close angular separations from their stars.Comment: published in A&

Accretion-ejection morphology of the microquasar SS 433 resolved at sub-au scale

This is the author accepted manuscript. the final version is available from EDP Sciences via the DOI in this recordWe present the first optical observation of the microquasar SS 433 at sub-milliarcsecond (mas) scale obtained with the GRAVITY instrument on the Very Large Telescope interferometer (VLTI). The 3.5-h exposure reveals a rich K-band spectrum dominated by hydrogen Brγand He i lines, as well as (red-shifted)emission lines coming from the jets. The K-band-continuum-emitting region is dominated by a marginally resolved point source (<1 mas) embedded inside a diffuse background accounting for 10% of the total flux. The jet line positions agree well with the ones expected from the jet kinematic model, an interpretation also supported by the consistent sign (i.e., negative/positive for the receding/approaching jet component) of the phase shifts observed in the lines. The significant visibility drop across the jet lines, together with the small and nearly identical phases for all baselines, point toward a jet that is offset by less than 0.5 mas from the continuum source and resolved in the direction of propagation, with a typical size of 2 mas. The jet position angle of ~80° is consistent with the expected one at the observation date. Jet emission so close to the central binary system would suggest that line locking, if relevant to explain the amplitude and stability of the 0.26c jet velocity, operates on elements heavier than hydrogen. The Brγprofile is broad and double peaked. It is better resolved than the continuum and the change of the phase signal sign across the line on all baselines suggests an East-West-oriented geometry similar to the jet direction and supporting a (polar) disk wind origin.Centre National d’Etudes Spatiales (CNES)Programme National Hautes Energies (PNHE)Humboldt FoundationNAS

Submilliarcsecond Optical Interferometry of the High-mass X-Ray Binary BP Cru with VLTI/GRAVITY

This is the final version. Available from American Astronomical Society via the DOI in this recordWe observe the high-mass X-ray binary (HMXB) BP Cru using interferometry in the near-infrared K band with VLTI/GRAVITY. Continuum visibilities are at most partially resolved, consistent with the predicted size of the hypergiant. Differential visibility amplitude () and phase () signatures are observed across the He i and Brγ lines, the latter seen strongly in emission, unusual for the donor star's spectral type. For a baseline m, the differential phase rms corresponds to an astrometric precision of . We generalize expressions for image centroid displacements and variances in the marginally resolved limit of interferometry to spectrally resolved data, and use them to derive model-independent properties of the emission such as its asymmetry, extension, and strong wavelength dependence. We propose geometric models based on an extended and distorted wind and/or a high-density gas stream, which has long been predicted to be present in this system. The observations show that optical interferometry is now able to resolve HMXBs at the spatial scale where accretion takes place, and therefore to probe the effects of the gravitational and radiation fields of the compact object on its environment

The wind and the magnetospheric accretion onto the T Tauri star S Coronae Australis at sub-Au resolution

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Aims. To investigate the inner regions of protoplanetary discs, we performed near-infrared interferometric observations of the classical T Tauri binary system S CrA. Methods. We present the first VLTI-GRAVITY high spectral resolution (R - 4000) observations of a classical T Tauri binary, S CrA (composed of S CrAN and S CrAS and separated by -10:04), combining the four 8m telescopes in dual-field mode. Results. Our observations in the near-infrared K-band continuum reveal a disc around each binary component, with similar halfflux radii of about 0.1 au at d - 130 pc, inclinations (i = 28 - 3-and i = 22 - 6-), and position angles (PA = 0- 6- and PA = -2-12-), suggesting that they formed from the fragmentation of a common disc. The S CrAN spectrum shows bright He i and Br line emission exhibiting inverse P Cygni profiles, typically associated with infalling gas. The continuum-compensated Br line visibilities of S CrAN show the presence of a compact Br emitting region whose radius is about -0.06 au, which is twice as big as the truncation radius. This component is mostly tracing a wind. Moreover, a slight radius change between the blue-And red-shifted Br line components is marginally detected. Conclusions. The presence of an inverse P Cygni profile in the He i and Br lines, along with the tentative detection of a slightly larger size of the blue-shifted Br line component, hint at the simultaneous presence of a wind and magnetospheric accretion in S CrA N.Science Foundation IrelandAlexander von Humboldt Foundation Fellowship ProgrammeFrench PNPSLabEx OSUG@202

Multiple star systems in the Orion nebula

This is the author accepted manuscript. The final fersion is available from EDP Sciences via the DOI in this record.This work presents an interferometric study of the massive-binary fraction in the Orion Trapezium cluster with the recently comissioned GRAVITY instrument. We observed a total of 16 stars of mainly OB spectral type. We find three previously unknown companions for θ1 Ori B, θ2 Ori B, and θ2 Ori C. We determined a separation for the previously suspected companion of NU Ori. We confirm four companions for θ1 Ori A, θ1 Ori C, θ1 Ori D, and θ2 Ori A, all with substantially improved astrometry and photometric mass estimates. We refined the orbit of the eccentric high-mass binary θ1 Ori C and we are able to derive a new orbit for θ1 Ori D. We find a system mass of 21.7 M⊙ and a period of 53 days. Together with other previously detected companions seen in spectroscopy or direct imaging, eleven of the 16 high-mass stars are multiple systems. We obtain a total number of 22 companions with separations up to 600 AU. The companion fraction of the early B and O stars in our sample is about two, significantly higher than in earlier studies of mostly OB associations. The separation distribution hints toward a bimodality. Such a bimodality has been previously found in A stars, but rarely in OB binaries, which up to this point have been assumed to be mostly compact with a tail of wider companions. We also do not find a substantial population of equal-mass binaries. The observed distribution of mass ratios declines steeply with mass, and like the direct star counts, indicates that our companions follow a standard power law initial mass function. Again, this is in contrast to earlier findings of flat mass ratio distributions in OB associations. We excluded collision as a dominant formation mechanism but find no clear preference for core accretion or competitive accretion.Marie Skłodowska-Curie Grant AgreementFCT-PortugalERC Starting Gran