Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus

BackgroundAutoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-cells (DNTs) (T-cell receptor αβ+ CD4−CD8−) and an increased risk of developing malignancies later in life.Case presentationWe herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.ConclusionWe described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms

Chemical and structural changes of pretreated empty fruit bunch (EFB) in ionic liquid-cellulase compatible system for fermentability to bioethanol

The pretreatment of empty fruit bunch (EFB) was conducted using an integrated system of IL and cellulases (IL-E), with simultaneous fermentation in one vessel. The cellulase mixture (PKC-Cel) was derived from Trichoderma reesei by solid-state fermentation. Choline acetate [Cho]OAc was utilized for the pretreatment due to its biocompatibility and biodegradability. The treated EFB and its hydrolysate were characterized by the Fourier transform infrared spectroscopy, scanning electron microscopy, and chemical analysis. The results showed that there were significant structural changes in EFB after the treatment in IL-E system. The sugar yield after enzymatic hydrolysis by the PKC-Cel was increased from 0.058 g/g of EFB in the crude sample (untreated) to 0.283 and 0.62 ± 06 g/g in IL-E system after 24 and 48 h of treatment, respectively. The EFB hydrolysate showed the eligibility for ethanol production without any supplements where ethanol yield was 0.275 g ethanol/g EFB in the presence of the IL, while lower yield obtained without IL-pretreatment. Moreover, it was demonstrated that furfural and phenolic compounds were not at the level of suppressing the fermentation process

3-Monochloropropane-1,2-diol (3-MCPD): a review on properties, occurrence, mechanism of formation, toxicity, analytical approach and mitigation strategy

3-Monochloropropane-1,2-diol (3-MCPD) is one of the most common food contaminants in processed oils which forms mostly during the deodorization step of edible oil refining process. It has been detected in many types of food products such as infant formula, margarine, bread and soy sauce, which could result in kidney and testicular damage. The presence of 3-MCPD contaminant have been occurring for more a decade, which warrants a maximum permissible amount of 2 µg/kg body weight in food products in national and international levels. The purpose of this review is to provide an overview in the past 12 years on its physicochemical properties, occurrence, potential precursors and formation mechanism of 3-MCPD in foodstuffs. The toxicity, its quantification methods and mitigation strategy are also reviewed with an emphasis on the applicability, efficiency and issues encountered during the analysis. This review provides an elucidation regarding 3-MCPDEs and their food safety implications