A clinical registry of multisystemic presentation of hypovitaminosis D in hospital attendees in Kolkata

Background: Vitamin D (Vit D) is a steroid hormone essential for maintaining functional homeostasis in the body. Hypovitaminosis D has been a recognized worldwide problem affecting all age groups and sex. Its prevalence is very high in South Asia. Aims and Objectives: Therefore, this study was aimed to determine the spectrum of presentation of biochemical levels of hypovitaminosis D in Indian population in terms of age, sex, and multisystemic disorders. Materials and Methods: A cross-sectional study carried out on selective study population attending a tertiary care hospital from July 2019 to December 2020 with clinical presentations suspected to arise due to Vit D deficiency. Serum 25OH Vit D level was estimated by chemiluminescence method. Data were analyzed using GraphPad Prism 8. Results: Of the study population (n = 685), average serum 25(OH)D level in females and males was 24.13 ng/ml and 28.59 ng/ml, respectively. Significant difference in mean value of Vit D existed in males and females in the 21–40 years age group (p = 0.0048). Females in the Vit D deficient group (Vit D level<20) mostly presented with mastalgia (20.45%), low back pain (17.61%), and joint pain (11.36%). Common clinical presentation in males with Vit D levels less than 20 ng/ml was diabetes mellitus without CKD (18.34%), non-diabetic CKD (19.27%), and low back pain (16.51%). Conclusion: Low Vit D levels manifest itself as signs and symptoms involving various multisystemic disorders involving different age groups in both sexes. Early recognition and replacement can prevent the progress of complications which Vit D deficiency makes us prone to develop.

Therapeutic Approaches in Lysosomal Storage Diseases

Lysosomal Storage Diseases are multisystemic disorders determined by genetic variants, which affect the proteins involved in lysosomal function and cellular metabolism. Different therapeutic approaches, which are based on the physiologic mechanisms that regulate lysosomal function, have been proposed for these diseases. Currently, enzyme replacement therapy, gene therapy, or small molecules have been approved or are under clinical development to treat lysosomal storage disorders. The present article reviews the main therapeutic strategies that have been proposed so far, highlighting possible limitations and future perspectives.

Inherited Platelet Disorders: An Updated Overview

Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 1011 platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes. Their clinical relevance is highly variable according to the specific disease and even within the same type, ranging from almost negligible to life-threatening. Mucocutaneous bleeding diathesis (epistaxis, gum bleeding, purpura, menorrhagia), but also multisystemic disorders and/or malignancy comprise the clinical spectrum of IPDs. The early and accurate diagnosis of IPDs and a close patient medical follow-up is of great importance. A genotype–phenotype relationship in many IPDs makes a molecular diagnosis especially relevant to proper clinical management. Genetic diagnosis of IPDs has been greatly facilitated by the introduction of high throughput sequencing (HTS) techniques into mainstream investigation practice in these diseases. However, there are still unsolved ethical concerns on general genetic investigations. Patients should be informed and comprehend the potential implications of their genetic analysis. Unlike the progress in diagnosis, there have been no major advances in the clinical management of IPDs. Educational and preventive measures, few hemostatic drugs, platelet transfusions, thrombopoietin receptor agonists, and in life-threatening IPDs, allogeneic hematopoietic stem cell transplantation are therapeutic possibilities. Gene therapy may be a future option. Regular follow-up by a specialized hematology service with multidisciplinary support especially for syndromic IPDs is mandatory.

SARS coronavirus 2: from genome to infectome

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the group of Betacoronaviruses. The SARS-CoV-2 is closely related to SARS-CoV-1 and probably originated either from bats or pangolins. SARS-CoV-2 is an etiological agent of COVID-19, causing mild to severe respiratory disease which escalates to acute respiratory distress syndrome (ARDS) or multi-organ failure. The virus was first reported from the animal market in Hunan, Hubei province of China in the month of December, 2019, and was rapidly transmitted from animal to human and human-to-human. The human-to-human transmission can occur directly or via droplets generated during coughing and sneezing. Globally, around 53.9 million cases of COVID-19 have been registered with 1.31 million confirmed deaths. The people > 60 years, persons suffering from comorbid conditions and immunocompromised individuals are more susceptible to COVID-19 infection. The virus primarily targets the upper and the lower respiratory tract and quickly disseminates to other organs. SARS-CoV-2 dysregulates immune signaling pathways which generate cytokine storm and leads to the acute respiratory distress syndrome and other multisystemic disorders.

Lysosomal sulfatases: a growing family*

Sulfatases constitute a family of enzymes that specifically act in the hydrolytic degradation of sulfated metabolites by removing sulfate monoesters from various substrates, particularly glycolipids and glycosaminoglycans. A common essential feature of all known eukaryotic sulfatases is the posttranslational modification of a critical cysteine residue in their active site by oxidation to formylglycine (FGly), which is mediated by the FGly-generating enzyme in the endoplasmic reticulum and is indispensable for catalytic activity. The majority of the so far described sulfatases localize intracellularly to lysosomes, where they act in different catabolic pathways. Mutations in genes coding for lysosomal sulfatases lead to an accumulation of the sulfated substrates in lysosomes, resulting in impaired cellular function and multisystemic disorders presenting as lysosomal storage diseases, which also cover the mucopolysaccharidoses and metachromatic leukodystrophy. Bioinformatics analysis of the eukaryotic genomes revealed, besides the well described and long known disease-associated sulfatases, additional genes coding for putative enzymes with sulfatases activity, including arylsulfatase G as well as the arylsulfatases H, I, J and K, respectively. In this article, we review current knowledge about lysosomal sulfatases with a special focus on the just recently characterized family members arylsulfatase G and arylsulfatase K.

P85 The effectiveness of group physiotherapy interventions for hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD): a service evaluation project

Background HSD and hEDS are complex and multisystemic disorders of connective tissue with arthralgia and other musculoskeletal features being acknowledged in the 2017 diagnostic criteria. Physiotherapy is a core component of management but there is no clear consensus regarding its effectiveness. For the last 21/2 years we have run an NHS group-based physiotherapy intervention consisting of four sessions focussing on patient education, exercises and lifestyle advice. The aim of this medical student-led project was to evaluate this service by canvassing patients' opinions and experiences and asking them to propose ways of improving care. Methods The physiotherapy intervention is open to all adults diagnosed with HSD and hEDS by rheumatologists or physiotherapists. 90 patients were invited to attend, and eleven groups were run between July 2017 and February 2019. To evaluate the service, patients were asked to complete an anonymised questionnaire which contained Likert scales (poor, average, good, very good or excellent) for four areas: (1) information on hypermobility; (2) pace of sessions; (3) physiotherapist's knowledge; and (4) relevance. In addition, free-text boxes asked about the patients' experiences of the course (likes, dislikes and suggested changes for future courses), and lessons learnt (lifestyle changes implemented, and take-home messages from the course). Results were recorded and analysed for recurring themes. Results 43 patients attended all four classes and 40 questionnaires were completed and returned. 100% rated the information on hypermobility and physiotherapist's knowledge as good, very good or excellent. Similarly, 94% rated the pace of sessions, and 97% the relevance of sessions as good, very good or excellent. Analysis of the free-text fields revealed three major themes: meeting people; effectiveness of the course; and lack of written information. Patients found it particularly valuable to meet others with similar concerns and experiences. They felt able to support each other by sharing and learning together, making them feel more comfortable with their condition. In terms of effectiveness of the course, they valued the information delivered about the condition and fatigue management. Patients reported benefit from learning exercises and relaxation techniques that they have built into their daily routines. Some patients came to realise that they can be active without causing injury and therefore incorporated regular exercise into their lifestyle. All patients reported actively implementing advice provided throughout the course. However, there was a lack of written information: patients requested leaflets relevant to the contents of classes. They also highlighted lack of information about the widespread effects of HSD/hEDS that they could share with friends, family and work colleagues. Conclusion Patients particularly valued learning alongside others with the same condition, and many reported actively implementing advice provided. An important area for development was written patient education and a resource pack needs generating to improve this. Disclosures D.M. Paxton None. R. Lewis None. S. Palmer None. E.M. Clark None.

Cerebellar Astrocytes: Much More Than Passive Bystanders In Ataxia Pathophysiology

Ataxia is a neurodegenerative syndrome, which can emerge as a major element of a disease or represent a symptom of more complex multisystemic disorders. It comprises several forms with a highly variegated etiology, mainly united by motor, balance, and speech impairments and, at the tissue level, by cerebellar atrophy and Purkinje cells degeneration. For this reason, the contribution of astrocytes to this disease has been largely overlooked in the past. Nevertheless, in the last few decades, growing evidences are pointing to cerebellar astrocytes as crucial players not only in the progression but also in the onset of distinct forms of ataxia. Although the current knowledge on this topic is very fragmentary and ataxia type-specific, the present review will attempt to provide a comprehensive view of astrocytes’ involvement across the distinct forms of this pathology. Here, it will be highlighted how, through consecutive stage-specific mechanisms, astrocytes can lead to non-cell autonomous neurodegeneration and, consequently, to the behavioral impairments typical of this disease. In light of that, treating astrocytes to heal neurons will be discussed as a potential complementary therapeutic approach for ataxic patients, a crucial point provided the absence of conclusive treatments for this disease.

Study of electronystagmography in the diagnosis and efficacy of follow-up after treatment, in patients with vertigo of peripheral origin

<p class="abstract"><strong>Background:</strong> Vertigo is a symptom of multisystemic disorders of various etiological factors with different clinical manifestations. The disorders causing the symptom may be of peripheral or central origin, and accurate diagnosis of the underlying pathology is warranted for effective treatment. Balance is a complex sensorimotor task involving accurate and redundant sensory input from the visual, vestibular and proprioceptive systems, central nervous system integration of the sensory signals and the generation of the appropriate motor commands and adequate musculoskeletal capabilities to perform the motor tasks involved in occulomotor and posture control.</p><p class="abstract"><strong>Methods:</strong> The study was conducted in the Department of Otorhinolaryngology, Regional Institute of Medical Sciences, Imphal, Manipur. 50 cases presenting with symptoms of vertigo were studied irrespective of age, sex and duration of illness in order to find out the cause of peripheral vertigo by using different diagnostic parameters with main emphasis on electronystagmography. All patients underwent pure tone audiometry for audiology assessment. The cases were treated and followed-up to a minimum period of 3 months, electronystagmography repeated during each visit to evaluate the efficacy and response to treatment. </p><p class="abstract"><strong>Results:</strong> Vertigo of peripheral origin comprised of 64%. Meniere’s disease was the largest group (28%) amongst the causes of peripheral vertigo. Subjective improvement of vertigo and electronystagmography was observed in all patients after treatment.</p><p class="abstract"><strong>Conclusions:</strong> Vertigo was most common in fourth decade of life and males have a slight predominance. Medical management was the mainstay of treatment. Patients with peripheral vertigo responded well to symptomatic and supportive treatment. Electronystagmography facilitates diagnosis of vertigo.</p>

Mast cell deposition and activation may be a new explanation for epiploic appendagitis

Epiploic appendagitis is as an acute painful condition of the fat on the outside of the intestine. Thus far, there have been no publications to our knowledge that appendagitis can be caused by mast cells or can be associated with chronic pain. A patient with multisystemic disorders suffered with both chronic and acute attacks of abdominal pain for a year. The worst attack led to surgical resection of an enlarged sigmoid colon epiploic appendage. Careful review of her complex medical history and mast cell stains of gastrointestinal biopsies led to the diagnosis of mast cell activation syndrome. Re-examination of the resected appendage using an immunohistochemical stain demonstrated a high mast cell density which is a new histopathological finding. Treatment of mast cell activation syndrome and other related syndromes led to marked improvement in her health, including all types of chronic abdominal pain.

Ptosis

Having droopy eyelids is a common problem. Causes may range from disorders that are simple and not progressive, such as congenital ptosis, to progressive, multisystemic disorders, such as mitochondrial disease. Myasthenia gravis (MG) is a very significant and treatable cause of ptosis that should always be part of the differential diagnosis. Apraxia of the eyelid opening can be confused with ptosis or blepharospasm, leading to a delay in reaching the correct diagnosis. Horner’s syndrome has different causes and management approaches. Knowledge of the anatomy and physiology of the eyelids is crucial for understanding the pathological processes that affect them.