Maple syrup urine disease (MSUD) is an autosomal recessive disorder associated with impaired metabolism of branched-chain amino acids (BCAA) leucine, isoleucine, and valine. Children with MSUD suffer from bouts of metabolic decompensation, which may lead to neurological damage. Liver transplantation from unrelated deceased donors has been considered curative. The natural history of the disease following transplantation using a haploidentical (obligate heterozygous) living donor is still unclear, although previously described as favorable. We describe acute metabolic crises in a 20-month-old child with MSUD type II. The first well-documented one occurred 5 months after a successful liver transplantation from his mother. The patient developed encephalopathy with progressive lethargy and seizures after an episode of gastroenteritis with dehydration. Plasma levels of leucine, isoleucine, and valine were markedly elevated and alloisoleucine was detected. He promptly responded to dialysis and BCAA-free dietetic management and subsequently could resume a normal diet. Since then he has had another symptomatic metabolic crisis with seizures. This case strongly suggests that some recipients of liver transplantation from a haploidentical parent possess limited capacity to oxidize BCAA at the time of catabolic stress and dehydration and remain at risk of severe metabolic crises. Thus, careful metabolic monitoring and prompt treatment post liver transplantation are still required to avoid neurological sequelae of MSUD, particularly if the donor is heterozygous for MSUD. Abbreviations BCAABranched-chain amino acids BCKDH Branched-chain keto acid dehydrogenase complex MSUD Maple syrup urine disease
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are oral hypoglycemic agents that have insulin-independent glucose-lowering effects mediated by increasing the renal excretion of glucose by inhibiting the SGLT2-mediated renal glucose reabsorption. An increasingly recognized complication induced by SGLT2i is euglycemic diabetic ketoacidosis (eDKA). Here, we describe the case of a 26-year-old male patient with type 2 diabetes mellitus and morbid obesity. Prior to presentation he was on multiple oral hypoglycemic agents including SGLT2i. He developed life-threatening severe prolonged eDKA associated with SGLT2i (Canagliflozin), precipitated by adenovirus infection. The acidosis was not responding to standard DKA therapy and renal replacement therapy but was managed effectively with insulin titration based on capillary ketone measurements. After reviewing the literature on severe prolonged eDKA induced by SGLT2 and treatment modalities used, we present previously reported cases similar to ours.
Here, we delineate the phenotype of two siblings with a bi‐allelic frameshift variant in MMP15 gene with congenital cardiac defects, cholestasis, and dysmorphism. Genome sequencing analysis revealed a recently reported homozygous frameshift variant (c.1058delC, p.Pro353Glnfs*102) in MMP15 gene that co‐segregates with the phenotype in the family in a recessive mode of inheritance. Relative quantification of MMP15 mRNA showed evidence of degradation of the mutated transcript, presumably by nonsense mediated decay. Likewise, MMP15: p.Gly231Arg, a concurrently reported homozygous missense variant in another patient exhibiting a similar phenotype, was predicted to disrupt zinc ion binding to the MMP‐15 enzyme catalytic domain, which is essential for substrate proteolysis, by structural modeling. Previous animal models and cellular findings suggested that MMP15 plays a crucial role in the formation of endocardial cushions. These findings confirm that MMP15 is an important gene in human development, particularly cardiac, and that its loss of function is likely to cause a severe disorder phenotype.
Background: Hearing loss (HL) is a heterogeneous condition that causes partial or complete hearing impairment. Hundreds of variants in >60 genes have been reported to be associated with Hereditary HL (HHL), variants of the GJB2 gene are the most common cause of congenital SNHL, with >100 variants reported.The HHL prevalence is thought to be high in the Arab population; however, the genetic epidemiology of HHL among Emirati populations is understudied.Aims: To shed light on the mutational spectrum of NSHL in Emirati patients seen in the genetic clinic over 10 years and to capture founder mutation(s) if any were identified. Methods: Retrospective chart review of all Emirati patients assessed by clinical geneticists due to NSHL during the period between January 2010 to December 2020. Genetic tests were done based on clinical phenotypes of the patient and family history including targeted mutation testing, next-generation sequencing, or whole-exome sequencing (solo or trio). The authors did literature reviews using PubMed for all previously reported articles related to NSHL genes from UAE.Results: A total of 162 patients with HL, were evaluated during the period between January 2010 to December 2020. There were 82 patients with NSHL, and only 72 patients who completed the genetic evaluations were included in this retrospective study. Among the studied group, 42 (51.2%) were males and 40 (48.78%) were females. The youngest patient was 2 years old and the oldest patient was 50 years old. Consanguinity was documented in 76 patients (92.68%). A total of 14 mutations reported here are novel (23/72 i.e., 31.9%). Twelve missense mutations, 6 nonsense mutations, 6 frameshift mutations, 2 in-frame deletion mutations, and 1 splice site mutation was found. Variants in the GJB2 gene are the most commonly identified cause of NSHL, with c.35delG being the most followed by c.506G > A. The second commonly found variant is c.934C > G (p.Arg312Gly) in the CDC14A gene, found in 9 patients. This was followed by variants in OTOF and SLC26A4 genes, found in 8 patients, respectively. Chromosomal microdeletions encompassing genes causing NSHL were found in 3 patients. No mitochondrial How to cite this article: Elsayed, O., & Al-Shamsi, A. (2022). Mutation spectrum of non-syndromic hearing loss in the UAE, a retrospective cohort study and literature review. Molecular Genetics & Genomic Medicine, 10, e2052.
A major goal of this study is to demonstrate how improving the quality of services can be used to enhance higher education institutions’ ability to hold on to their students and assist them in graduating on time. This study investigates the relationship between service quality and student retention in the higher education sector, as well as the influences of satisfaction, trust, and commitment on this relationship. The study discusses how Institutions can retain their students while defining service quality in the present day. Hence, the literature focused on how service quality impacts student retention today. Following the literary phase of the research, the framework specifies the study’s methodology while analyzing the importance of service quality in higher education institutions. It aims to identify the key success factor contributing to student retention and completion of graduation in higher education through a critical assessment of service quality literature. It suggests a theoretical framework using the SERVQUAL model. A qualitative method of four focus groups was conducted. The data were analyzed using coding, and the hypotheses were constructed and discussed qualitatively. The study concluded that service quality is crucial to retaining students in higher education. According to the research, service quality is important to establishing assurance with students. This study highlights the significance of operational aspects in the service sector, particularly for high-contact services. Furthermore, it demonstrates how higher education institutions can achieve long-term sustainability while providing expansion opportunities.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.