Cerebral lipid accumulation in Chanarin-Dorfman Syndrome

Chanarin-Dorfman Syndrome (CDS) is caused by a defect in the CGI-58/ABHD5 gene resulting in a deficiency of CGI-58 and in intracellular accumulation of triacylglycerol in skin and liver. Patients are mainly characterized by congenital ichthyosis, but the clinical phenotype is very heterogeneous. Distinct brain involvement has never been described. We present a clinical description of two patients with congenital ichthyosis. On suspicion of Sjögren-Larsson syndrome (SLS) single-voxel 1H-MR spectroscopy of the brain was performed and biochemical testing of fatty aldehyde dehydrogenase (FALDH) to establish this diagnosis gave normal results. Vacuolisation in a peripheral blood smear has led to the CDS suspicion. In both patients the diagnosis CDS was confirmed by ABHD5 mutation analysis. Interestingly, a clear lipid accumulation in the cerebral white matter, cortex and basal ganglia was demonstrated in both CDS-patients. These results demonstrate, for the first time, cerebral involvement in CDS and give new insights in the complex phenotype. Since the clinical implications of this abnormal cerebral lipid accumulation are still unknown, further studies are warranted.status: publishe

Thirty years of the human immunodeficiency virus epidemic and beyond

After more than 30 years of battling a global epidemic, the prospect of eliminating human immunodeficiency virus (HIV) as the most challenging infectious disease of the modern era is within our reach. Major scientific discoveries about the virus responsible for this immunodeficiency disease state, including its pathogenesis, transmission patterns and clinical course, have led to the development of potent antiretroviral drugs that offer great hopes in HIV treatment and prevention. Although these agents and many others still in development and testing are capable of effectively suppressing viral replication and survival, the medical management of HIV infection at the individual and the population levels remains challenging. Timely initiation of antiretroviral drugs, adherence to the appropriate therapeutic regimens, effective use of these agents in the pre and post-exposure prophylaxis contexts, treatment of comorbid conditions and addressing social and psychological factors involved in the care of individuals continue to be important considerations

Fission-Track Thermochronology Applied to the Evolution of Passive Continental Margins

International audiencePassive continental margins (PCMs) form at divergent plate boundaries in response to continental breakup and subsequent formation of new oceanic basins. The onshore topography of PCMs is a key component to understand the evolution of extensional settings. The classic nomenclature of PCMs is derived from early investigations that suggested apparent tectonic stability after the initial phase of rifting and breakup. However, geological and geomorphic diversity of PCMs requires more complex models of rift and post-rift evolution. Fission-track (FT) thermochronology provides appropriate tools to decipher the long-term development of PCM topography and better resolve the spatial and temporal relationships between continental erosion and sediment accumulation in adjacent offshore basins. FT datasets have revealed complex spatial and temporal denudation histories across some PCMs and have shown that several kilometres of material may be removed from the onshore margin following rifting. Combining these data with geological and geomorphological observations, and with predictions from numerical modelling, suggests that PCMs may have experienced significant post-rift activity. Case histories illustrated in this chapter include the PCM of southeastern Africa and the conjugate PCMs of the North and South Atlantic