Molecular and clinical analysis of ALPL in a cohort of patients with suspicion of Hypophosphatasia.

Hypophosphatasia (HPP) is a rare autosomal dominant or recessive metabolic disorder caused by mutations in the tissue nonspecific alkaline phosphatase gene (ALPL). To date, over 300 different mutations in ALPL have been identified. Disease severity is widely variable with severe forms usually manifesting during perinatal and/or infantile periods while mild forms are sometimes only diagnosed in adulthood or remain undiagnosed. Common clinical features of HPP are defects in bone and tooth mineralization along with the biochemical hallmark of decreased serum alkaline phosphatase activity. The incidence of severe HPP is approximately 1 in 300,000 in Europe and 1 in 100,000 in Canada. We present the clinical and molecular findings of 83 probands and 28 family members, referred for genetic analysis due to a clinical and biochemical suspicion of HPP. Patient referrals included those with isolated low alkaline phosphatase levels and without any additional clinical features, to those with a severe skeletal dysplasia. Thirty-six (43.3%) probands were found to have pathogenic ALPL mutations. Eleven previously unreported mutations were identified, thus adding to the ever increasing list of ALPL mutations. Seven of these eleven were inherited in an autosomal dominant manner while the remaining four were observed in the homozygous state. Thus, this study includes a large number of well-characterized patients with hypophosphatasemia which has permitted us to study the genotype:phenotype correlation. Accurate diagnosis of patients with a clinical suspicion of HPP is crucial as not only is the disease life-threatening but the patients may be offered bone targeted enzymatic replacement therapy. © 2017 Wiley Periodicals, Inc.

Risk factors for hepatitis C virus acquisition and predictors of persistence among Egyptian children.

BACKGROUND: Hepatitis C virus (HCV) has a lower prevalence in children and knowledge is limited regarding the natural outcome of HCV infection in children. AIM: To study the risk factors of HCV acquisition and predictors of persistence in Egyptian children. METHODS: Children, 1-9 years of age, were evaluated for acquisition of HCV (anti-HCV positive regardless of viraemia) and persistence of HCV (anti-HCV and HCV-RNA positive) at two paediatric hepatology clinics in Cairo at enrollment and at 3 monthly intervals. Spontaneous clearance of HCV was defined as ≥ two positive anti-HCV antibody tests with negative HCV-RNA at least 6 months apart. RESULTS: Over a 33-month-period a total of 226 children <9 years of age were screened for HCV antibodies. Of those, 146 (65%) were anti-HCV positive of which 87 (60%) were HCV-RNA positive. The HCV acquisition was more likely to occur in older children (P = 0.003) with comorbid conditions (P < 0.01) compared to anti-HCV negative children. In a multivariate logistic regression analysis, the highest risk factors for HCV acquisition were surgical interventions [odds ratio (OR): 4.7] and blood transfusions (OR: 2.3). The highest risk factor for HCV persistence was dental treatment (OR: 16.9) and male gender (OR: 7.5). HCV persistence was also strongly associated with elevated baseline alanine aminotransaminase (ALT) levels (OR: 4.9) and fluctuating aspartate aminotransferase (AST) levels (OR: 8.1). CONCLUSION: Although surgical interventions and blood transfusion are significant risk factors for HCV acquisition in Egyptian children, dental treatment remains the highest risk factor for HCV chronic persistence in children.

Comparison Between Silicone Oil and Gas in Tamponading Giant Retinal Breaks.

PURPOSE: The purpose of this study is to compare anatomical and visual outcomes after using silicone oil (SO) or C3F8 gas as tamponades after pars plana vitrectomy (PPV) for retinal detachment (RD) associated with giant retinal tears (GRTs). METHODS: A retrospective chart review was conducted for cases that underwent PPV for GRT-associated RD. We excluded eyes that had prior vitreoretinal surgery, a history of ocular trauma or worse than grade B proliferative vitreoretinopathy (PVR). Baseline demographic and ocular characteristics, surgical details and postoperative anatomical and visual outcomes were recorded and statistically analyzed. RESULTS: We included 88 eyes; 48 eyes had C3F8 gas and 40 eyes had SO as a tamponading agent. Mean age was 39 years. All eyes underwent 23G PPV with no adjuvant scleral buckling and phacovitrectomy was performed for all phakic eyes. Final retinal reattachment was achieved in 86 eyes (97.7%). One eye from each group had recurrent RD. Postoperative vision was significantly better in the gas group (p= 0.008). Prolonged increase of IOP developed in 6 eyes in the SO group and 5 eyes in the gas group. Prolonged uveitis developed in 4 eyes in the gas group and 6 eyes in the oil group (P= 0.04). Epiretinal membranes (ERM) developed in 10 eyes in the gas group and 9 eyes in the oil group. We found no significant difference between both groups regarding postoperative glaucoma or ERM formation. CONCLUSION: Both agents achieved similar favorable anatomical outcomes in a series of eyes with fresh GRT-associated RD and low-grade PVR, with better visual outcome and less frequent uveitis associated with the use of gas tamponade.

DRD2/ANKK1 TaqI polymorphism and smoking behavior of Egyptian male cigarette smokers.

Little is known about the genetic contribution to cigarette smoking and nicotine addiction in Egypt. The dopamine D2 receptor gene contains a TaqI repeat fragment length polymorphism creating two alleles with functional significance, DRD2*A1 and DRD2*A2. We investigated the relationship between these alleles and tobacco use in a study of 389 Egyptian male current smokers (mean age = 40 years; SD = 12). Participants were interviewed in 2004 on their smoking behaviors and quit attempts, and were given the Fagerström Test for Nicotine Dependence (FTND). Blood samples were obtained and genotyped for DRD2 A1and A2 alleles. The frequencies of A1/A2, A1/A2, and A2/A2 genotypes were 6%, 29%, and 65%, respectively. We found no statistically significant association between genotype and age at onset of smoking, years of smoking, FTND score, or average number of cigarettes smoked per day. DRD2 genotype was associated with the number of cigarettes smoked in the past 48 hr (42.2 in A1 carriers vs. 37.6 in A2, p = .03), the previous quit duration (28% in A1 vs. 40% in A2 quit for more than 1 month, p = .05), and the depth of inhalation (82% in A1 vs. 72% in A2 inhaled the smoke deeply, p = .03). Logistic regression analysis including DRD2 genotype, FTND score, age at smoking initiation, marital status, and education as predictors showed that maximum duration of quit time was associated with FTND score (p = .003), DRD2 genotype (p = .01), marital status (p = .03), and age at smoking initiation (p = .04). These findings suggest a modest association between DRD2 genotype and quitting behavior in male cigarette smokers in Egypt.

Surveillance of acute hepatitis C in Cairo, Egypt.

Surveillance of acute hepatitis has been set up in two fever hospitals in Cairo to diagnose acute hepatitis C. Patients were categorized as definite acute hepatitis C with positive hepatitis C virus (HCV) RNA and without anti-HCV antibody, or probable acute hepatitis C with positive HCV RNA, positive anti-HCV antibody, alanine aminotransferase >/=4 times the upper limit of normal (ULN), and high risk parenteral exposure in the 1--3 months prior to the beginning of symptoms. From May to November 2002, 315 patients were recruited in the study. Of these, 115 (36.5%) had acute hepatitis A, 89 (28.3%) had acute hepatitis B, and 111 (35.2%) had non-A non-B acute hepatitis. Of the total with complete data (n=309), 12 (3.9%, 95% CI=2.0%-6.7%) had definite acute hepatitis C, and 11 (3.6%, 95% CI=1.8%-6.3%) had probable acute hepatitis C. In patients with definite acute hepatitis C, dental exposure (n=5) and intravenous drug use (n=2), were the only high risk procedures found in the 6 months prior to diagnosis. Five patients had no identifiable parenteral exposure. In conclusion, results from this study suggest that acute hepatitis C can be diagnosed by surveillance of acute hepatitis in hospital settings in Cairo and that minor community exposures contribute substantially to local HCV transmission.