Background The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. Methods We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify the independent predictors. Results A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95%CI 1.1-11), use of systemic steroids (aOR 7.7,95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6,95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. Conclusion Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

Congenital disorders of glycosylation (CDG) are an extremely rapidly growing and phenotypically versatile group of disorders. Conserved oligomeric Golgi (COG) complexes are hetero-octameric proteins involved in retrograde trafficking within the Golgi. Seven of its eight subunits have a causal role in CDG. To date, only three cases of COG8-CDG have been published but none in the antenatal period. We present the first case of antenatally diagnosed COG8-CDG with facial dysmorphism and additional features such as Dandy-Walker malformation and arthrogryposis multiplex congenita, thus expanding the phenotype of this rare disorder. Trio whole exome sequencing revealed a novel homozygous variant in COG8, which creates a new splice site in exon 5 and protein truncation after 12 amino acids downstream to the newly generated splice site. As the mutations of the previous three patients were also identified in exon 5, it is likely to be a potential mutational hotspot in COG8. An association between antenatally increased nuchal translucency and COG8-CDG is also established, which would alert clinicians to its diagnosis early in gestation.It remains to be seen if this observation can be extended to other COG-CDGs. K E Y W O R D Santenatal presentation, arthrogryposis multiplex congenita, COG8-CDG, Dandy-Walker malformation, increased NT, mutational hotspot

BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are one of the most common malformations identified in the fetal stage. Bilateral renal agenesis (BRA) represents the most severe and fatal form of CAKUT. Only three genes have been confirmed to have a causal role in humans (ITGA8, GREB1L, and FGF20).MethodsGenome sequencing within a diagnostic setting and combined data repository analysis identified a novel gene.ResultsTwo patients presented with BRA, detected during the prenatal period, without additional recognizable malformations. They had parental consanguinity and similarly affected, deceased siblings, suggesting autosomal recessive inheritance. Evaluation of homozygous regions in patient 1 identified a novel, nonsense variant in GFRA1 (NM_001348097.1:c.676C>T, p.[Arg226*]). We identified 184 patients in our repository with renal agenesis and analyzed their exome/genome data. Of these 184 samples, 36 were from patients who presented with isolated renal agenesis. Two of them had loss-of-function variants in GFRA1. The second patient was homozygous for a frameshift variant (NM_001348097.1:c.1294delA, p.[Thr432Profs*13]). The GFRA1 gene encodes a receptor on the Wolffian duct that regulates ureteric bud outgrowth in the development of a functional renal system, and has a putative role in the pathogenesis of Hirschsprung disease.ConclusionsThese findings strongly support the causal role of GFRA1-inactivating variants for an autosomal recessive, nonsyndromic form of BRA. This knowledge will enable early genetic diagnosis and better genetic counseling for families with BRA.

IntroductionVitamin D is increasingly recognized to have several beneficial effects. Vitamin D deficiency is widely prevalent. Physicians often treat patients with high doses of vitamin D for various ailments without any monitoring for adverse effects and the prescribed doses often far exceed requirements resulting in toxicity. We present here a classic case of iatrogenic hypervitaminosis D, which presented with persistent vomiting and acute renal failure.Case presentationHere we present a case of a 45-year-old Asian Indian woman who presented to us with persistent vomiting the cause of which was iatrogenic hypervitaminosis D. She was treated with intravenous fluid, diuretics and calcitonin and had clinical improvement.ConclusionsWe suggest that in any patient presenting with persistent vomiting and hypercalcemia, particularly in the presence of normal parathyroid hormone, a diagnosis of overdose of vitamin D should be suspected. Its treatment not only alleviates symptoms but also prevents ongoing acute kidney injury.

AI is present in more than half of cirrhotic patients but does not parallel the severity scores of cirrhosis. Its presence predicts early mortality in these patients, and this prediction is independent of CTP or MELD scores.

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Wiedemann-Steiner syndrome (WWS) is a rare disorder characterized by hypotonia, postnatal growth restriction, striking facial dysmorphism, and hirsutism. It is caused by heterozygous pathogenic variants in KMT2A. This gene has an established role in histone methylation, which explains the overlap of WWS with syndromes caused by genes involved in chromatin remodeling. We describe an infant with a novel single base pair deletion in KMT2A with features consistent with WWS, as well as additional features of stenosis of aqueduct of Sylvius and broad toes. The usefulness of Face2Gene as a tool for identification of dysmorphology syndromes is discussed, as in this patient, it suggested WWS as the top candidate disorder. To the best of our knowledge, this is the first patient of WWS reported from India, with a novel genotype and expanded phenotype. K E Y W O R D S aqueduct stenosis, broad toes,

Background and aims:The clinical profile of patients with hepatocellular carcinoma (HCC) may differ depending on the etiology of HCC. There is no study from India comparing the clinical profile of patients of HCC due to hepatitis B virus (HBV) infection with other etiologies. Methods: We retrospectively reviewed the records of patients clinically diagnosed as HCC between Nov 2000 and Dec 2012 admitted under a single unit of Department of Gastroenterology at our hospital. We compared the clinical presentation of patients of Hepatitis B virus etiology (HBV group) with other etiologies (Non-HBV group). Results: One hundred and forty-two patients were included (median age 60 years [range 30-83], 92% males). The etiology was HBV in 56 (39%) and among the non-HBV group (n = 86, 61%) the etiological spectrum was following: alcohol 31 (22%), cryptogenic 26 (18%), HCV 27 (19%), and miscellaneous 2 (1%). The median age of presentation was significantly less for HBV group than in non-HBV (56 vs. 62 [42-83] years, P < 0.01). Clinical evidence of cirrhosis was significantly less common in the HBV group than non-HBV group (74% vs 98%, P < 0.01). HBV group had lower CTP score than non-HBV (median CTP score 7 vs 8,P < 0.05). Ascites was more common in non-HBV group than HBV group (65% vs 43%, P = 0.018). The BCLC staging was: A 13%, B 23%, C 35%, and D 29%, and there was no difference in tumor characteristics or BCLC staging between HBV or the non-HBV group. Conclusions: HBV is a common cause of HCC in India, accounting for 39% of cases. The tumor characteristics of HCC due to HBV is similar to other etiologies, however, HBV causes HCC at an earlier age, and in less advanced or even absence of cirrhosis, thus further consolidating the directly carcinogenic potential of HBV. ( J CLIN EXP HEPATOL 2013;3:288-295)