Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations.

Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 affected patients from 38 unrelated Sudanese families segregating multiple forms of SCDs. The age-at-onset in our cohort ranged from birth to 35 years; however, most patients manifested childhood-onset diseases (the mean and median ages at onset were 7.5 and 3 years, respectively). We reached the genetic diagnosis in 63% and possibly up to 73% of the studied families when considering variants of unknown significance. Combining the present data with our previous analysis of 25 Sudanese HSP families, the success rate reached 52-59% (31-35/59 families). In this article we report candidate variants in genes previously known to be associated with SCDs or other phenotypically related monogenic disorders. We also highlight the genetic and clinical heterogeneity of SCDs in Sudan, as we did not identify a major causative gene in our cohort, and the potential for discovering novel SCD genes in this population.

Follicular Variant of Acquired Dermal Macular Hyperpigmentation: A Case Report.

Acquired dermal macular hyperpigmentation (ADMH) is a term used to describe a group of diseases that are characterized by idiopathic macular dermal hypermelanosis. These skin conditions include erythema dyschromicum perstans, lichen planus pigmentosus, and pigmented contact dermatitis, also known as Riehl's melanosis. This case report involves a 55-year-old woman who was generally healthy but who had been experiencing asymptomatic, slowly progressive skin lesions for the previous four years. A thorough inspection of her skin revealed many non-scaly, pin-point follicular brown macules, which in some spots had coalesced into patches across her neck, chest, upper extremities, and back. Darier disease and Dowling-Degos disease were included in the differential diagnosis. The biopsies of the skin revealed follicular plugging. The dermis had pigment incontinence with melanophages and slight perivascular and perifollicular mononuclear cell infiltrates. The patient was diagnosed with a follicular form of ADMH. Patient's skin condition caused her concern. She was reassured and prescribed topical steroids 0.1% betamethasone valerate ointment application twice a day for two days per week (weekends) and 0.1% tacrolimus ointment application twice a day for five days per week for three months. She showed some improvement and was put under periodic follow-ups.

ACE2 and TMPRSS2 SNPs as Determinants of Susceptibility to, and Severity of, a COVID-19 Infection.

Background: Genetic risk factors may be related to the infectivity and severity of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) and host transmembrane serine protease (TMPRSS2) have key role in viral cell entrance and priming. Methods: This case-control study on 147 healthy controls and 299 COVID-19 patients identified potential determinants and risk factors, including gene polymorphism involved in the severity (mild, moderate, severe) of COVID-19 disease defined by CORAD radiological criteria. Results: The ACE2 s2285666 and TMPRSS2 rs12329760 SNPs were significantly linked with COVID-19 disease severity, as were certain co-morbidities (hypertension, heart disease) and laboratory parameters. Both SNPs were amongst the highest predictors of disease severity: TMPRSS2 rs12329760 CT + TT [odds ratio (95% CI) 17.6 (5.1-61.10), ACE2 rs2285666 CT + TT 9.9 (3.2-30.9), both p < 0.001]. There was an increase in the expression of genotype frequencies of ACE2 rs2285666 and TMPRSS2 rs1232976 (TT), (CT + TT), and (T) allele in severe COVID-19 group compared to control and mild groups. Disease severity was also linked to elevated CRP, ferritin and D-dimer, and lower lymphocytes and platelet count (all p < 0.001). Conclusion: ACE2 rs2285666 and TMPRSS2 rs12329760 SNPs, in addition to lymphocyte count, CRP, D-dimers, ferritin, and hypertension, are predictors of COVID-19 disease severity.

Alveolar Paratesticular Rhabdomyosarcoma in an Adult Patient Mimicking Epididymo-Orchitis: A Case Report and a Literature Review.

The majority of patients with paratesticular rhabdomyosarcoma (RMS) present in the pediatric age group with a unilateral, painless, palpable scrotum mass. By contrast, cases of RMS presenting as painful edema are rare. We present a case of alveolar paratesticular RMS in a 30-year-old man who had been suffering from a painful swelling of the scrotum on the left side for two years and a preceding mass four months before visiting the clinic. Complete resection of the left epididymal mass was performed through a left inguinal incision. The histopathological and immunohistochemical examination of the mass revealed alveolar RMS of the paratesticular region. Urologists should be aware that paratesticular RMS may present in adults with atypical symptoms such as scrotal pain and edema, especially in those who do not respond to antibiotics. Hence, such patients should have an additional evaluation.

Trends in the Incidence of Nasopharyngeal Cancer in Saudi Arabia Across One Decade (2007 to 2016).

Background Cancer is an ongoing global health concern; it is the greatest cause of mortality in the industrialized world and the second-highest cause of death in the developing world. This study aims to assess the incidence and geographic distribution of nasopharyngeal cancer between 2007 and 2016 in Saudi Arabia. Methods Data between 2007 and 2016 from Saudi Cancer Registry reports were collected in this study. These reports provide information on all cancer cases, including the age, sex, geographic location, and year of diagnosis for each patient. Result Between 2007 and 2016, the Saudi Cancer Registry identified 110,075 cancer cases in total. The mean age-standardized rate of all cancer types for women was 51.7 compared with 48.2 for men. The percentage of cases of nasopharyngeal cancers was 1.2% for women and 2.2% for men in 2007. This percentage decreased to 0.8% for women and increased to 2.7% for men in 2016 in comparison to all cancer cases. The curve for nasopharyngeal cancer of all cancer types for men and women correlated with rises and drops in men over the study period, and a minor decrease in women over time, until another rise in 2016. A positive correlation was observed between nasopharyngeal cancer incidence and age. The age-standardized rate data for nasopharyngeal cancer cases demonstrated a wide variation across Saudi regions. The age-standardized rate per 100,000 people from 2007 to 2016 ranged from 0.39 in Jazan to 1.92 in Qassim, with a national average of 1.06. Conclusion From 2007 to 2016, the overall trend of the age-standardized rate for men fluctuated while the female rate slightly dropped before rising again. On the contrary, the incidence of nasopharyngeal cancer varies by region in Saudi Arabia. Further study of this variation would help focus awareness campaigns on the most susceptible regions.

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and Precocious Puberty With a Third Ventricle Arachnoid Cyst.

Arachnoid cyst (AC) is a rare defect of the central nervous system that accounts for 1% of all intracranial lesions, of which only 1% of reported cases are located in the third ventricle. Endocrine manifestations associated with AC include precocious puberty, growth hormone deficiency, and hypothalamic dysfunction. We report a child who presented with a visual field defect, hyponatremia, and precocious puberty related to a third ventricle AC. Hyponatremia as a complication of AC is rare. A literature review revealed two case reports of Syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with suprasellar AC. The pathophysiology of SIADH in AC is not well understood. Hyponatremia may worsen following endoscopic fenestration of the AC secondary to changes in intracranial pressure. In conclusion, hyponatremia with AC should be recognized during the preoperative and postoperative periods and may require treatment with hypertonic saline in addition to fluid restriction.

Guillain-Barré Syndrome in an Elderly Patient as a Complication of COVID-19 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infection that mainly affects the respiratory system. It may present with fever, fatigue, dry cough, and dyspnea. In addition, numerous studies and case reports discussed those viruses showing their effects on the nervous system. In this report, we present a case of a 66-year-old Saudi man who had been recovering from symptoms related to coronavirus 2019 (COVID-19) associated disease. He was presented with sudden progressive ascending weakness that started in the left leg, and it spread to involve both legs and then both arms, five days prior to hospitalization. Lumbar puncture and nerve conduction studies showed that the patient has an acute motor-sensory axonal neuropathy (AMSAN) variant of Guillain-Barré syndrome (GBS). The patient was treated with intravenous immunoglobulin (IVIG) and supportive care. The patient was discharged after 15 days of hospitalization with clinical improvement. In conclusion, to our knowledge, this study investigated the first reported case of GBS in an elderly patient as a complication of COVID-19 infection in Saudi Arabia, with the most severe variant AMSAN. As the COVID-19 pandemic continues, clinicians should consider GBS as a neurological complication of COVID-19, and therapy must be initiated. Further studies are needed to study the possible mechanism of GBS in patients with COVID-19 in the future.

Chronic Vomiting and Weight Loss Due to Cecal Pinworm Infestation: A Case Report and Brief Literature Review.

Enterobius vermicularis (E. vermicularis), also called pinworm or threadworm, is a widespread parasitic infection that has infected approximately 40 million individuals in the United States. However, the infection is rarely seen in the adult population. An atypical presentation of Enterobius vermicularis (E. vermicularis) infection has been reported previously in children and infants. However, there are no previous reports of this infection among adults in the Middle East. We present a case of a 30-year-old Saudi male patient who presented with significant weight loss, diarrhea, and vomiting. A colonoscopy revealed E. vermicularis in the cecum. The patient received one dose of oral albendazole 400 mg and then a repeat dose in two weeks based on his colonoscopy findings. The patient was seen in an outpatient clinic and reported complete resolution of postprandial vomiting. Asking about risk factors if there is any contact with contamination is essential. In addition, colonoscopy and stool analysis may also be considered to confirm the diagnosis. However, future studies investigating the incidence and risk factors of this infection are warranted as similar studies reporting this infection in Saudi Arabia are limited. Proper diagnosis and treatment are also essential to prevent complications of the infection.

Steroid therapy in children with fulminant hepatitis A.

Fulminant hepatic failure is a life-threatening disease. Hepatitis A virus (HAV) can cause fulminant hepatic failure and death in about 0.2% of cases. Extensive destruction of infected hepatocytes by immune-mediated lysis is thought to be the cause. We aimed to evaluate the use of steroid therapy in children with fulminant HAV. This study included 33 children with fulminant HAV in two groups. Steroid group: comprised of 18 children who received prednisolone (1 mg/kg/d) or its equivalent dose of methylprednisolone, and the nonsteroid group: comprised another 15 children who did not receive steroid therapy. Age and sex were matched for both groups (P > .05), and they were comparable regarding baseline clinical and laboratory characteristics. Of the steroid group, 15 patients survived and 3 died, while in the nonsteroid group, 4 patients survived and 11 died (P = .001). Of the living patients, 15 of 19 (78.9%) received steroids while only 3 of 14 (21.4%) of the dead patients received steroids (P = .001). Stepwise regression analysis showed that steroid therapy was the only independent variable associated with recovery (P = .001). Steroid therapy in children with fulminant HAV associated significantly with improved outcome and survival. Future studies on a larger population size are strongly recommended.

How to Manage a Dysfunction of the Efferent Segment in Continent Cutaneous Urinary Diversion (Hydraulic Reservoir)? A Retrospective Study of 10 Cases

"Continent cutaneous reservoirs after cystectomy remain an invaluable treatment option for a well-defined subset of indications. The continence mechanism largely determines the treatment success in terms of patient satisfaction and quality of life. Any dysfunction is considered a failure by both patients and surgeons. A retrospective study was made from 2003 to 2013 (13 years) with the aim to characterize the hydraulic valve dysfunction in patients who underwent a cystectomy with continent urinary pouch. A total of ten patients were included in this study. The main age was 44 years. The indications of cystectomy were pelvic tumors (62%); vesico-vaginal fistulas (20%); bladder extrophy (10%); hypospadias (4%) and complicated uretral strictures (4%). An hydraulic continent valve according the Benchekroun process was made for all our patients. After a median follow-up of 36 months; the main related efferent segment complications were fistulas in the top of the valve or ""pinhole fistula"" in 25% of cases; the externalized prolapse of disinserted valve in 25% of cases; and the progressive desinvagination with urinary incontinence in 50% of cases Continent catheterizable urinary diversion remains a treatment option for a well-defined subset of indications. There is little consensus regarding the different options for the efferent segment; which has the greatest influence on patient satisfaction."

Impact of Interleukin-28B gene polymorphism (rs12979860) on Egyptian patients infected with hepatitis C virus genotype-4.

Single nucleotide polymorphisms (SNPs) in the Interleukin (IL)-28B gene, namely rs12979860, could predict response to pegylated interferon-α-ribavirin (PR) therapy in hepatitis C virus genotype 1 (HCV-1)-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype (CC) was associated with sustained viral response (SVR) to therapy compared with the homozygous T allele genotype (TT) and the heterozygous genotype (CT). In the SVR group, the response rate was statistically significantly higher in CC genotypes (58.6%) compared with CT/TT (20.3%). There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy.

Dietary fat intake, circulating and membrane fatty acid composition of healthy Norwegian men and women.

BACKGROUND: The present study aimed to assess the dietary fat intake and blood fatty acid status of healthy Norwegian men and women living in Bergen whose habitual diet is known to be high in long-chain omega-3 fat. METHODS: Healthy men (n = 41) and women (n = 40) aged 20-50 years who were regular blood donors completed 7-day food diaries and their nutrient intake was analysed by Norwegian food database software, kbs, version 4.9 (kostberegningssystem; University of Oslo, Oslo, Norway). Blood samples were obtained before blood donation and assessed for the fatty acid composition of plasma triglycerides and cholesterol esters, phosphatidylcholine, and red cell phosphatidylcholine and phosphatidylethanolamine. RESULTS: There was no difference in dietary fat intake between men and women. Total and saturated fat intakes exceeded the upper limits of the recommendations of the National Nutrition Council of Norway. Although polyunsaturated fat intake was close to the lower limit of the recommended level, the intake varied greatly among individuals, partly as a result of the use of supplementary fish oil. Moreover, the proportional fatty acid composition of plasma and red cell lipids was similar between men and women. Enrichment of docosahexaenoic acid in red cell phosphatidylethanolamine was found in fish oil users. CONCLUSIONS: The results of the present study provide a snapshot of the current nutritional status of healthy Norwegian adults. Moreover, the detailed blood fatty acid composition of men and women whose habitual diet constitutes high long-chain polyunsaturated omega-3 fat as well as saturated fat could be used as reference value for population studies.

Impact of Interleukin-28B gene polymorphism (rs12979860) on Egyptian patients infected with hepatitis C virus genotype-4

Single nucleotide polymorphisms [SNPs] in the Interleukin [IL]-28B gene, namely rs12979860, could predict response to pegylated interferon-?-ribavirin [PR] therapy in hepatitis C virus genotype 1 [HCV-1]-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype [CC] was associated with sustained viral response [SVR] to therapy compared with the homozygous T allele genotype [TT] and the heterozygous genotype [CT]. In the SVR group, the response rate was statistically significantly higher in CC genotypes [58.6%] compared with CT/TT [20.3%]. There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy. We underscore IL28B genotyping as a tool that might increase PR cost-benefit in Egypt

Natural radioactivity and chemical concentrations in Egyptian groundwater.

Measurements of natural radioactivity in drinking water have been performed in many parts of the world, mostly for assessment of the doses and risk resulting from consuming water. A study of the radionuclide and chemical components in groundwater from Beni Suef Governate, Egypt has been carried out. Fifty water samples were analyzed by gamma ray spectroscopy to determine the 226Ra, 232Th, and 40K concentrations; major elements, pH, alkalinity, and conductivity were also measured. The specific activity values ranged from 0.008 to 0.040 Bq/l for 226Ra, from 0.003 to 0.019 Bq/l for 232Th, and from 0.025 to 0.344 Bq/l for 40K. The annual ingestions of these radionuclides, using local consumption rates (average over the whole population) of 1.5 l day(-1), were estimated to be 8.59, 4.86, and 83.47 Bq year(-1) for 226Ra, 232Th, and 40K, respectively. The estimated values and weighted means of these radionuclides compare well with the world average. The estimated effective doses from drinking water were found to be 2.4 µSv year(-1) (226Ra), 1.1 µSv year(-1) (232Th), and 0.51 µSv year(-1) (40K). Contribution of these radionuclides to the committed effective dose from 1 year consumption of drinking water is estimated to be only 4%.

[Persistent Müllerian ducts syndrome]. / Syndrome de persistance des canaux de Müller.

Persistent Müllerian ducts syndrome is a rare form of internal male pseudohermaphroditism, characterized by the presence of the uterus, fallopian tubes and upper vagina in an otherwise normally virilised male with a 46 XY karyotype. It is the result of a deficiency in anti-Müllerian hormone or abnormality of this hormone receptor. Often, the diagnosis is made incidentally during surgical exploration for cryptorchidism or herniorrhaphy, and exceptionally during cancer of ectopic testis. We discuss a rare case of this syndrome revealed by a bilateral intra-abdominal gonadal tumor.

Analysis of common MEFV mutations in Egyptian patients with familial Mediterranean fever: molecular characterisation of the disease.

Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder transmitted as an autosomal recessive trait. It predominantly affects people living in, or originating from, areas around the Mediterranean and was difficult to diagnose until mutations in the MEFV gene were identified. This study aims to analyse the five most common MEFV mutations in Egyptian patients diagnosed clinically as FME Thirty-eight unrelated patients were tested for the presence of the MEFV gene mutations V726A, M694V, M694I, M680I and E148Q, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the amplification refractory mutation system (ARMS). Twenty-three patients (60.5%) had one or more mutations, whereas no mutation was found in the remaining 15 patients (39.5%). The most common mutation was M694I (42.5%), followed by V726A (22.5%), M680I (17.5%) and E148Q (17.5%). The M694V mutation was not detected. The profile of MEFV gene mutations in this study suggests that the origin of FMF in Egypt is heterogeneous, a finding in concordance with that for other Arab populations; however, some differences were observed as M694V, the most common mutation reported in Arabs, was not detected in this study.

Natural radioactive nuclides and chemical components in the groundwater of Beni Suef Governate, Middle Egypt.

Measurements of natural radioactivity in drinking water have been performed in many parts of the world, mostly for assessment of the doses and risk resulting from consuming water. A study of the radionuclide and chemical components in groundwater from Beni Suef Governate, Egypt has been carried out. Fifty water samples were analysed by gamma-ray spectroscopy to determine the (226)Ra, (232)Th and (40)K concentrations; major elements, pH, alkalinity and conductivity were also measured. The activity concentration values ranged from 0.008 to 0.040 Bq l(-1) for (226)Ra, from 0.003 to 0.019 Bq l(-1) for (232)Th and from 0.025 to 0.344 Bq l(-1) for (40)K. The annual ingestion of these radionuclides, using local consumption rates (averaged over the whole population) of 1.5 l d(-1), was estimated to be 8.59, 4.86 and 83.47 Bq y(-1) for (226)Ra, (232)Th and (40)K, respectively. The estimated effective doses from drinking water were found to be 2.4 microSv y(-1) ((226)Ra), 1.1 microSv y(-1) ((232)Th) and 0.5 microSv y(-1) ((40)K). The contribution of these radionuclides to the committed effective dose from a year's consumption of drinking water is therefore estimated to be only 4% of the WHO value (0.1 mSv y(-1)). The moderate pH value is the most important parameter, and there was no observed correlation between natural radioactivity and electrical conductivity or concentrations of major ions.

Telomerase activity, and tissue polypeptide specific antigen (TPS) in Egyptian breast cancer patients.

OBJECTIVES: Breast cancer is the most common malignancy among Egyptian women. The aim of this study is to evaluate the role of both telomerase and TPS estimation in assessment of breast cancer. METHODS: The study included 40 patients with breast cancer, and 20 patients with benign breast diseases. Telomerase activity in breast tissues was assessed using TRAP assay. TPS was measured in sera of the patients by ELISA. RESULTS: Telomerase positivity was 15% in benign group vs. 60% in malignant group (p = 0.0009). It was significantly correlated to stage, and lymph node status (p < 0.02). Telomerase positivity showed significant correlation to tumor recurrence (p = 0.0076) in a follow-up period of 36 months. Mean rank of TPS was significantly higher in malignant than benign groups (p < 0.001), and in telomerase positive than telomerase negative patients (p < 0.001). In malignant group, mean rank of TPS was significantly higher in late stages (p < 0.002), in higher grade (p < 0.05), in larger tumor size (p < 0.01), and in lymph node positive patients (p < 0.001). ROC curve was utilized to choose the best cutoff for serum TPS (88 U/L). At this cutoff, the sensitivity was 95%, and the specificity was 75%. At a higher cutoff (109 U/L), TPS positivity was significantly correlated to stage, grade, lymph node status, and telomerase positivity (p < 0.05). CONCLUSION: Telomerase positivity and serum TPS might be used as additional markers for assessment of breast cancer.