Here we demonstrate biallelic mutations in sorbitol dehydrogenase (SORD) as the most frequent recessive form of hereditary neuropathies. We identified 45 cases from 38 families across multiple ethnicities, carrying a particular nonsense mutation in SORD, c.753delG; p.Ala253GlnfsTer27, either in homozygous or compound heterozygous state with a second variant. With an allele frequency of 0.004 in healthy controls, the p.Ala253GlnfsTer27 variant represents one of the most common pathogenic alleles in humans. SORD is an enzyme that converts sorbitol into fructose, in the two-step polyol pathway that has been implicated in diabetic neuropathy. In patient-derived fibroblasts, we find a complete loss of SORD protein as well as increased intracellular sorbitol. Also, serum fasting sorbitol level was over 100 times higher in patients homozygous for the p.Ala253GlnfsTer27 mutation compared to healthy individuals. In Drosophila, we show that loss of SORD orthologues causes synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a potentially treatable cause in a significant fraction of patients with inherited neuropathies and may contribute to a better understanding of the pathophysiology of diabetic neuropathy.

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A total of 437 patients with epilepsy were identified, 30.7% of whom (n=134/437) were uncontrolled, with a prevalence of 2.1/1000. A total of 52.2% of uncontrolled patients (n=70/134) were inappropriately treated, while 47.8% (n=64/134) were compliant with appropriate treatments. Video monitoring EEG of compliant uncontrolled patients demonstrated that 78.1% patients (n=50/64) had definite epilepsy, while 21.9% (n=14/64) had psychogenic non-epileptic seizures (PNES). A logistic regression analysis revealed that status epilepticus, focal seizures, and mixed seizure types were risk factors for intractability.

Mucormycosis is a life-threatening opportunistic angioinvasive fungal infection. We aimed to describe the frequency, presentations, predictors, and in-hospital outcome of mucormycosis patients in the scope of CoronaVirusDisease-19 (COVID-19) during the third viral pandemic wave. This cross-sectional retrospective study included all patients who fulfilled the criteria of mucormycosis with concurrent confirmed covid19 infection admitted to Assuit University Hospital between March 2021 and July 2021. Overall, 433 patients with definite covid-19 infection, of which 33 (7.63%) participants were infected with mucormycosis. Mucormycosis was predominantly seen in males (21 vs. 12; p = 0.01). Diabetes mellitus (35% vs. 63.6%; p < 0.001), hypertension (2% vs.45.5%; p 0.04), and Smoking (26.5% vs. 54.5%; p < 0.001) were all significantly higher in mucormycosis patients. Inflammatory markers, especially E.S.R., were significantly higher in those with mucormycosis (p < 0.001). The dose of steroid intake was significantly higher among patients with mucormycosis (160 mg vs. 40 mg; p < 0.001). Except for only three patients alive by residual infection, 30 patients died. The majority (62%) of patients without mucormycosis were alive. Male sex; Steroid misuse; D.M.; Sustained inflammation; Severe infection were significant risk factors for mucormycosis by univariate analysis; however, D.M.; smoking and raised E.S.R. were predictors for attaining mucormycosis by multivariate analysis.

Background Mild mitral stenosis (MS) is a progressive disease but unfortunately, its clinical course is still unclearly studied. We aimed to study the left atrial (LA) deformation in such patients and how it is related to exercise intolerance. Methods Seventy‐five patients with mitral valve area of 1.81 ± 0.13 cm2 and 40 healthy control subjects were enrolled. All participants had sinus rhythm, and they underwent conventional echocardiography and LA strain analysis with speckle‐tracking study. The following parameters were obtained: left atrial reservoir strain (LAS‐s), LA conduit strain (LAS‐e), and LA contraction strain (LAS‐a). All participants underwent symptoms limited stress ECG using modified Bruce protocol. Results Comparing with control subjects, patients with mild MS had significant lower LAS‐s value (P < .01) and LAS‐e (<0.03). Patients with exercise intolerance (METs < 8) had lower LAS‐s (P < .001), LAS‐e (P < .01), and LAS‐a (P < .05) values compared to those with METs ≥ 8. We found that METs was significantly related to LAS‐s (P < .001), brain natriuretic peptide (P < .001), and Δ TAPSE (P < .03). Multivariate analysis showed that LAS‐s was an independent predictor of reduced exercise capacity. With ROC analysis, LAS‐s ≤ 26.5% was the optimal value for prediction of exercise intolerance in patients with mild MS. Conclusion A significant percentage of patients with mild mitral stenosis had exercise intolerance. We found that LAS‐s was significantly associated with exercise capacity in patients with mild MS. Hence, we thought that LA deformation could be of great value in the follow‐up of patients with mild MS.