Reviewing the Clinical Spectrum Related to Kmt2b Gene Mutations: Unusual Clinical Presentation and a Possible New Pathogenic Mutation

Introduction KMT2B related dystonia is a childhood onset generalized dystonia. Since its first description in 2016, different phenotypic spectrum have been reported. The aim of the case report is to provide data that may help to understand the spectrum of KMT2B-related disorders. We present two members of a family with a possible non-previously described pathogenic mutation and an unusual KMT2B related dystonia presentation: an adult onset and focal dystonia.Case Presentation The index patient is a 32 year-old woman with a generalized dystonia. Her maternal uncle presented a focal dystonia. Next-generation sequencing revealed a heterozygous missense mutation in KMT2B gene (19q13.12), described as a variant of uncertain significance (VUS). Although characteristic phenotype of KMT2B dystonia is a childhood onset generalized dystonia, different phenotypes have been related according to the kinds of mutations in this gene, also varying the age of symptom onset and the penetrance of the mutation. Asymptomatic or sub-clinical carriers and adult onset has been described. Due to the low prevalence of this variant in the general population and the low penetrance and high intrafamilial variability of this entity, we suggest that this mutation might be a pathogenic variant.ConclusionsKMT2B related dystonia is an emerging and prevalent monogenic dystonia whose incidence, genetic variability and clinical spectrum remain unknown. Despite the study of this gene is indicated in childhood onset dystonia, description of cases such as ours shows that its sequencing in patients with an adult-onset dystonia with family history can be useful for the diagnosis.

Clinical spectrum and outcomes of patients with different resistance patterns of Salmonella enterica

Background and Objective: Unceasing rise in cases of enteric fever, in particular extensively drug resistant (XDR) strain of Salmonella enterica, has led to a growing threat, leaving only carbapenems and azithromycin as the precious option. In this regard, we determined the burden and clinical course of XDR salmonella in comparison to multidrug-resistant (MDR) and drug sensitive (DS) strains. Methods: A retrospective chart review of 1515 Salmonella Typhi (S.typhi) culture positive patients was conducted at Indus Hospital and Health Network, Karachi from July 2017 to December 2018. Results: During our study, we observed children at the age of 5-6 years and adults at the age of 20-22 years were the chief targets of S.typhi. Further, we witnessed a rapid shift of drug resistance from MDR to XDR over the one year of study. Almost all patients presented with fever. However other signs and symptoms like malaise, body aches, anorexia, diarrhea, vomiting and abdominal pain were more common in XDR Typhoid patients. Further, the need of hospitalization, total hospital stay and mortality was also greater for XDR typhoid patients. Conclusion: There is a crucial requirement for consolidated steps to curtail the spread of XDR Salmonella tyhi disease as its management is challenging, and it is associated with increased morbidity and mortality. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5789 How to cite this:Herekar F, Sarfaraz S, Imran M, Ghouri N, Shahid S, Mahesar M. Clinical spectrum and outcomes of patients with different resistance patterns of Salmonella enterica . Pak J Med Sci. 2022;38(2):356-361. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5789 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Consequence of COVID-19

SARS-CoV-2 is the third and largest pandemic that emerged in Wuhan city, Hubei province, China in 2019. As per WHO 45,988,595 people have been infected and the COVID 19 has caused more than 1,194,979 deaths. The clinical spectrum of COVID 19 varies from asymptomatic presentation to multi-organ dysfunction. The pathophysiology behind the sequel of COVID 19 immuno-suppression is an area yet to be explored. Here, we report a case of 52 year old male with persistent pyrexia post his recovery from COIVD-19. On further evaluation, a diagnosis of amoebic liver abscess that resulted as a sequel of COVID-19 was made.

Clinical spectrum of endemic leptospirosis in relation to cytokine response

Objectives To describe the clinical spectrum and the cytokine response of leptospirosis patients in an endemic setting of Sri Lanka. Methods Patients presenting to the university teaching hospital, Anuradhapura, Sri Lanka with a leptospirosis-compatible illness were recruited over a period of 12 months starting from June 2012. Daily clinical and biochemical parameters of the patients were prospectively assessed with a follow-up of 14 days after discharge. A magnetic bead–based multiplex cytokine kit was used to detect 17 cytokines. Results Of the 142 clinically suspected leptospirosis patients recruited, 47 were confirmed and, 29 cases were labeled as “probable.” Thrombocytopenia and leukocytosis were observed at least once during the hospital stay among 76(54%) and 39(28%) patients, respectively. Acute kidney injury was observed in 31 patients (22%) and it was significantly higher among confirmed and probable cases. Hu TNF-α and IL-1β were detected only in patients without complications. Hu MIP-1b levels were significantly higher among patients with complications. During the convalescence period, all tested serum cytokine levels were lower compared to the acute sample, except for IL-8. The cytokine response during the acute phase clustered in four different groups. High serum creatinine was associated GM-CSF, high IL-5 and IL-6 level were correlates with lung involvement and saturation drop. The patients with high billirubin (direct)>7 mmol/l had high IL-13 levels. Conclusions Results of this study confirms that the knowledge on cytokine response in leptospirosis could be more complex than other similar tropical disease, and biosignatures that provide diagnostic and prognostic information for human leptospirosis remain to be discovered.