Hemochromatosis Mimicked Gaucher Disease: Role of Hyperferritinemia in Evaluation of a Clinical Case

Gaucher disease is a disorder of lysosomes caused by a functional defect of the glucocere-brosidase enzyme. The disease is mainly due to mutations in the GBA1 gene, which determines the gradual storage of glucosylceramide substrate in the patient’s macrophages. In this paper, we describe the case of a 38-year-old man who clinically presented with hyperferritinemia, thrombocytopenia, leukopenia, anemia and mild splenomegaly; a diagnosis of hemochromatosis was made 10 years earlier. Re-evaluation of the clinical case led to a suspicion of Gaucher disease, which was confirmed by enzymatic analysis, which was found to be below the normal range, and genetic evaluation, which identified compound heterozygosity N370S/RecNciI. We know that patients suffering from Gaucher disease can also have high ferritin levels. Even if the mechanism underlying the changes in iron metabolism is not yet elucidated, the chronic mild inflammatory state present in these patients probably causes the storage of ferritin in macrophages, resulting in hyperferritinemia. Therefore, in the presence of few typical signs and symptoms of the disease should raise an alarm bell in the clinicians, inducing clinical suspicion of Gaucher disease. Misdiagnosis and diagnostic delay in metabolic diseases could cause irreversible organ damage and delay the start of specific therapy for these patients

Thermal anomalies and fluid geochemistry framework in occurrence of the 2000-2001 Nizza Monferrate seismic sequence (northern Italy): Episodic changes in the fault zone heat flow or chemical mixing phenomena?

International audienceThe paper discusses the correlation between the heating of shallow groundwater over a 10 × 20 km wide area close to the town of Nizza Monferrato (Piemonte Region, Northern Italy) and the concomitant local seismic sequences during the period August 2000 ? July 2001. The first seismic sequence started on 21 August 2000 with a Ml = 5.2 earthquake. Within few hours, the local authorities received calls alerting that the groundwater temperature rose from 10 to 30°C in many shallow wells. Our geochemical experimental data and the geological-seismotectonic framework do not allow the hypothesis of simple fluid mixing between the thermal reservoir of Acqui Terme and the Nizza-Monferrato shallow groundwater to explain the observed thermal anomalies. On the other hand, we invoke more complex processes such as frictional heating, mechano-chemistry, fault-valve mechanism, adiabatic decompression and hydrogeologically driven heat flow i.e., thermal effects due to variations of basin-scale permeability field. All these processes are able to transmit heat to the surface and to generate a transient incremental heat flow better than the mass transfer occurring typically when fluids from different reservoirs mix

Tracking Formation of a Lava Lake From Ground and Space: Masaya Volcano (Nicaragua), 2014–2017

A vigorously degassing lava lake appeared inside the Santiago pit crater of Masaya volcano (Nicaragua) in December 2015, after years of degassing with no (or minor) incandescence. Here we present an unprecedented-long (3 years) and continuous volcanic gas record that instrumentally characterizes the (re)activation of the lava lake. Our results show that, before appearance of the lake, the volcanic gas plume composition became unusually CO2 rich, as testified by high CO2/SO2 ratios (mean: 12.2 ± 6.3) and low H2O/CO2 ratios (mean: 2.3 ± 1.3). The volcanic CO2 flux also peaked in November 2015 (mean: 81.3 ± 40.6 kg/s; maximum: 247 kg/s). Using results of magma degassing models and budgets, we interpret this elevated CO2 degassing as sourced by degassing of a volatile-rich fast-overturning (3.6–5.2 m3 s−1) magma, supplying CO2-rich gas bubbles from minimum equivalent depths of 0.36–1.4 km. We propose this elevated gas bubble supply destabilized the shallow (<1 km) Masaya magma reservoir, leading to upward migration of vesicular (buoyant) resident magma, and ultimately to (re)formation of the lava lake. At onset of lava lake activity on 11 December 2015 (constrained by satellite-based MODIS thermal observations), the gas emissions transitioned to more SO2-rich composition, and the SO2 flux increased by a factor ∼40% (11.4 ± 5.2 kg/s) relative to background degassing (8.0 kg/s), confirming faster than normal (4.4 versus ∼3 m3 s−1) shallow magma convection. Based on thermal energy records, we estimate that only ∼0.8 of the 4.4 m3 s−1 of magma actually reached the surface to manifest into a convecting lava lake, suggesting inefficient transport of magma in the near-surface plumbing system

Escalating CO2 degassing at the Pisciarelli fumarolic system, and implications for the ongoing Campi Flegrei unrest

This short communication aims at providing an updated report on degassing activity and ground deformation variations observed during the ongoing (2012–2019) Campi Flegrei caldera unrest, with a particular focus on Pisciarelli, currently its most active fumarolic field. We show that the CO2 flux from the main Pisciarelli fumarolic vent (referred as “Soffione”) has increased by a factor > 3 since 2012, reaching in 2018–2019 levels (>600 tons/day) that are comparable to those typical of a medium-sized erupting arc volcano. A substantial widening of the degassing vents and bubbling pools, and a further increase in CO2 concentrations in ambient air (up to 6000 ppm), have also been detected since mid-2018. We interpret this escalating CO2 degassing activity using a multidisciplinary dataset that includes thermodynamically estimated pressures for the source hydrothermal system, seismic and ground deformation data. From this analysis, we show that degassing, deformation and seismicity have all reached in 2018–2019 levels never observed since the onset of the unrest in 2005, with an overall uplift of ~57 cm and ~448 seismic events in the last year. The calculated pressure of the Campi Flegrei hydrothermal system has reached ~44 bar and is rapidly increasing. Our results raise concern on the possible evolution of the Campi Flegrei unrest and reinforce the need for careful monitoring of the degassing activity at Pisciarelli, hopefully with the deployment of additional permanent gas monitoring units

Dynamics of Outgassing and Plume Transport Revealed by Proximal Unmanned Aerial System (UAS) Measurements at Volcán Villarrica, Chile

Volcanic gas emissions are intimately linked to the dynamics of magma ascent and outgassing, and, on geological timescales, constitute an important source of volatiles to the Earth’s atmosphere. Measurements of gas composition and flux are therefore critical to both volcano monitoring and to determining the contribution of volcanoes to global geochemical cycles. However, significant gaps remain in our global inventories of volcanic emissions, (particularly for CO2, which requires proximal sampling of a concentrated plume) for those volcanoes where the near-vent region is hazardous or inaccessible. Unmanned Aerial Systems (UAS) provide a robust and effective solution to proximal sampling of dense volcanic plumes in extreme volcanic environments. Here, we present gas compositional data acquired using a gas sensor payload aboard a UAS flown at Volcán Villarrica, Chile. We compare UAS-derived gas timeseries to simultaneous crater rim multi-GAS data and UV camera imagery to investigate early plume evolution. SO2 concentrations measured in the young proximal plume exhibit periodic variations that are well-correlated with the concentrations of other species. By combining molar gas ratios (CO2/SO2 = 1.48–1.68, H2O/SO2 = 67–75 and H2O/CO2 = 45–51) with the SO2 flux (142 ± 17 t/day) from UV camera images, we derive CO2 and H2O fluxes of ~150 t/day and ~2850 t/day, respectively. We observe good agreement between time-averaged molar gas ratios obtained from simultaneous UAS- and ground-based Multi-GAS acquisitions. However, the UAS measurements made in the young, less diluted plume reveal additional short-term periodic structure that reflects active degassing through discrete, audible gas exhalations.Alfred P. Sloan Foundation; Leverhulme Trus

Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease

Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker. The levels of miR-126-3p contained in small extracellular vesicles (sEVs), with about 130 nm of diameter, were measured in FD patients and healthy subjects divided into age classes, in vitro, in human umbilical vein endothelial cells (HUVECs) "young" and undergoing replicative senescence, through a quantitative polymerase chain reaction (qPCR) approach. We confirmed that, in vivo, circulating miR-126 levels physiologically increase with age. In vitro, miR-126 augments in HUVECs underwent replicative senescence. We observed that FD patients are characterized by higher miR-126-3p levels in sEVs, compared to age-matched healthy subjects. We also explored, in vitro, the effect on ECs of glycosphingolipids that are typically accumulated in FD patients. We observed that FD storage substances induced in HUVECs premature senescence and increased of miR-126-3p levels. This study reinforces the hypothesis that FD may aggravate the normal aging process

Genetic screening of Fabry patients with EcoTILLING and HRM technology

<p>Abstract</p> <p>Background</p> <p>Anderson-Fabry disease (FD) is caused by a deficit of the α-galactosidase A enzyme which leads to the accumulation of complex sphingolipids, especially globotriaosylceramide (Gb3), in all the cells of the body, causing the onset of a multi-systemic disease with poor prognosis in adulthood. In this article, we describe two alternative methods for screening the <it>GLA </it>gene which codes for the α-galactosidase A enzyme in subjects with probable FD in order to test analysis strategies which include or rely on initial pre-screening.</p> <p>Findings</p> <p>We analyzed 740 samples using EcoTILLING, comparing two mismatch-specific<ul/>endonucleases, CEL I and ENDO-1, while conducting a parallel screening of the same samples using HRM (High Resolution Melting). Afterwards, all samples were subjected to direct sequencing. Overall, we identified 12 different genetic variations: -10C>T, -12G>A, -30G>A, IVS2-76_80del5, D165H, C172Y, IVS4+16A>G, IVS4 +68 A>G, c.718_719delAA, D313Y, IVS6-22C>T, G395A. This was consistent with the high genetic heterogeneity found in FD patients and carriers. All of the mutations were detected by HRM, whereas 17% of the mutations were not found by EcoTILLING. The results obtained by EcoTILLING comparing the CEL I and ENDO-1 endonucleases were perfectly overlapping.</p> <p>Conclusion</p> <p>On the basis of its simplicity, flexibility, repeatability, and sensitivity, we believe that<ul/>HRM analysis of the <it>GLA </it>gene is a reliable presequencing screening tool. This method can be applied to any genomic feature to identify known and unknown genetic alterations, and it is ideal for conducting screening and population studies.</p

Spatial Distribution of Field Physico-Chemical Parameters in the Vulcano Island (Italy) Coastal Aquifer: Volcanological and Hydrogeological Implications

Vulcano, the southernmost of the Aeolian island arc (Italy), is characterized by a shallow coastal aquifer resulting from the mixing of seawater, meteoric recharge and volcanogenic fluids. The aquifer has been intensively studied during the last decades, but a comprehensive hydrogeological model has never been developed due to the lack of direct information about the litho-stratigraphic columns of the wells and the depth of water bearing levels. We present and discuss here the time and spatial analysis of water table elevation, temperature and electric conductivity data, acquired during the last 20 years in 33 wells located at Vulcano Island, with the aim of developing a groundwater circulation scheme able to fit the field observations. We retrieved a circulation scheme characterized by an intricate geometry of flow paths driven by horizontal and vertical permeability variations, accounting for the strong variability of geochemical data evidenced in this area by the related scientific literature. Extending these results to a general context, particular care must be taken in approaching the study of aquifers in volcanic islands, because a strong, small spatial scale variability of the hydrogeochemical parameters is expected, and a reliable knowledge of the local conditions is required for developing successful groundwater circulation schemes.Published3206-32244V. Vulcani e ambienteJCR Journalope

Tracking Formation of a Lava Lake From Ground and Space: Masaya Volcano (Nicaragua), 2014–2017

A vigorously degassing lava lake appeared inside the Santiago pit crater of Masaya volcano (Nicaragua) in December 2015, after years of degassing with no (or minor) incandescence. Here we present an unprecedented-long (3 years) and continuous volcanic gas record that instrumentally characterizes the (re)activation of the lava lake. Our results show that, before appearance of the lake, the volcanic gas plume composition became unusually CO 2 rich, as testified by high CO 2 /SO 2 ratios (mean: 12.2 ± 6.3) and low H 2 O/CO 2 ratios (mean: 2.3 ± 1.3). The volcanic CO 2 flux also peaked in November 2015 (mean: 81.3 ± 40.6 kg/s; maximum: 247 kg/s). Using results of magma degassing models and budgets, we interpret this elevated CO 2 degassing as sourced by degassing of a volatile-rich fast-overturning (3.6–5.2 m 3 &nbsp;s −1 ) magma, supplying CO 2 -rich gas bubbles from minimum equivalent depths of 0.36–1.4 km. We propose this elevated gas bubble supply destabilized the shallow (&lt;1 km) Masaya magma reservoir, leading to upward migration of vesicular (buoyant) resident magma, and ultimately to (re)formation of the lava lake. At onset of lava lake activity on 11 December 2015 (constrained by satellite-based MODIS thermal observations), the gas emissions transitioned to more SO 2 -rich composition, and the SO 2 flux increased by a factor ∼40% (11.4 ± 5.2 kg/s) relative to background degassing (8.0 kg/s), confirming faster than normal (4.4 versus ∼3 m 3 &nbsp;s −1 ) shallow magma convection. Based on thermal energy records, we estimate that only ∼0.8 of the 4.4 m 3 &nbsp;s −1 of magma actually reached the surface to manifest into a convecting lava lake, suggesting inefficient transport of magma in the near-surface plumbing system

Mutations in the GLA gene and LysoGb3: Is it really Anderson-Fabry disease?

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme &#945;-galactosidase A (&#945;-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the &#945;-Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. &#945;-Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, &#945;-Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease