Screening for phenylketonuria and galactosemia among Egyptian newborns in Menoufiya governorate

Aim of the Work: Was to study the prevalence of phenylketonuria and galactosemia in Menoufiya Governorate newborns. Among 3000 newborns, their mean ages were 9.3±2.43 days; mean weight was 3.1 ±0.82 Kg. Among them 1800( 60% ) males and 1200 (40% ) females who attended the central hospital and medical units for BCG vaccination in the duration from March 2005 to May 2008.Results: The results showed that the mean of phenylalanine levelwas 3.19 ±1.82 mg/dl and the mean total galactose level was 3.34 ± 2.23mg/ dl, among the 3000 neonates, 2183 (72.8. %) had phenylalanine levels ranging from 2-5 mg /dl, 705 (23.5%) had levels ranging from 5-7 mg/dl, 111(3.7%) had levels ranging from 7-10 mg/dl and one newborn (0.033%) had phenylalanine level of 22 mg/dl. The results for galactosemia screening assay showed that 2528 neonates (84.3%) had galactose levels ranging from 2-6 mg/dl, 450 (15%) had levels ranging from 6-8 mg/dl, 21(0.7%) had levels ranging from 8-12 mg/dl and one newborn (0.033%) had galactose level of 19 mg/dl. The child was reassayed and was found to be true hypergalactosemia 120mg/dl.Conclusion: We concluded that the prevalence of each of phenylketonuria and galactosemia in Menoufiya Governorate in the 3000 newborn tested was 1/3000 (0.03%). So, we estimate that about 333 neonates are affected every year with PKU and 333 with galactosemia as one million babies are born yearly, which could be prevented. The prevention of such treatable disorders depends on planning an efficient screening programme especially within three weeks after birth. So we recommend multicenter studies to encourage national neonatal screening programmes specialy for these treatable diseases.Key Words: Phenylketonuria, galactosemia, hepatomegaly, neonatal screening

Inborn errors of metabolism revealed by organic acid profile analysis in high risk Egyptian patients: Six years experience

Objective: To determine the prevalence and types of inborn errors of amino acid or organic acid metabolism in a group of high risk Egyptian children with clinical signs and symptoms suggestive of inherited metabolic diseases. Subjects and Methods: 117 (79 males ═ 67.5 % and 38 females ═ 32.5 %) high risk patients with signs and symptoms of a metabolic disorder were studied, their ages ranged from 3 days to 12 years. Analysis of urine organic acids by gas chromatography/mass spectrometry (GC/MS) was performed to all patients. Results: 22(18.8 % of the total) cases were diagnosed with different types of aminoacidopathies or organic acidurias. The disease profile showed increased lactate in 12 cases (54 %), glutaric aciduria type I 3cases (13 %), phenylketonuria 2 cases (9 %), maple syrup urine disease 1 case (4.5 %), glutaric aciduria type II 1 case (4.5 %), methylmalonic aciduria 1 case (4.5 %), Canavan disease 1 case (4.5 %) and non ketotic hyperglycemia 1 case (4.5 %). Conclusion: The results demonstrate the importance of the organic acid profile in the diagnosis of high risk patients. The diagnosed organic acid pattern in this study showed that 10.2 % of the patients had a mitochondrial energy defect.Key Words: Organicacidurias, organicacidemias, gas chromatography/mass spectrometry, organic acid profile analysis

Fifteen years experience: Egyptian metabolic lab

Background: Inborn errors of metabolism (IEM) are single gene disorders responsible for abnormalities in the synthesis or catabolism of proteins, carbohydrates and fats by means of defective enzymes or transport proteins which results in a block of the metabolic pathway and accumulation of metabolites in different tissues. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population. Prior to 1995, the diagnosis of inherited metabolic disorders in Egypt was very limited and diagnosed mainly on clinical suspicion. In 1995, The Biochemical Genetics Unit at The National Research Centre has been established as a part of The Human Genetics Department and later on in 2003 it was developed into The Biochemical Genetics Department by applying advanced techniques and equipments and providing early diagnosis for the metabolic disorders which led to better outcome in our patients. Material and methods: We have retrospectively reviewed a total of 12,148 cases suspected to have inborn errors of metabolism (IEM) with different age groups. They had been referred from several diagnostic centers and hospitals in Egypt to The Department of Biochemical Genetics at The National Research Centre. The diagnosis of these disorders was confirmed by qualitative determination of amino acid profile, quantitative determination of phenylalanine and galactose levels using dried blood spots (DBSs), quantitative determination of urinary glycosaminoglycans (GAGs), twodimensional electrophoretic separation of GAGs in urine and the assay for lysosomal enzymes activities in plasma and leukocytes. Results: Out of the total number of cases; 1041 (8.6%) patients were proved to have metabolic disorders. Those patients were classified as: 722 patients (69.4%) with lysosomal storage disorders, 302 patients (29%) with amino acid disorders and 17 patients (1.6%) with galactosemia. Conclusion: This study illustrates the experience of the reference metabolic lab in Egypt over 15 years. The lab began metabolic disorder screening by using simple diagnostic techniques like thin layer chromatography and colored tests in urine which by time updated and upgraded the methods to diagnose a wide range of disorders. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population.Keywords: IEM; Consanguineous marriages; Aminoacidopathies; Lysosomal storage disorder

Porphyrins profile by high performance liquid chromatography/electrospray ionization tandem mass spectrometry for the diagnosis of porphyria

Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway. Most porphyria symptoms are nonspecific and occur intermittently; resulting frequently in missed diagnosis since the disease itself is a rare one. The aim of the study is toestablish a new reliable and accurate laboratory method for separation, identification and quantitation of urinary porphyrins by liquid chromatography tandem mass spectrometry (LC/MS/MS) and thereby the diagnosis of different porphyria types for the first time in Egypt. Screening by plasma fluorescence and quantitative determination of urinary porphyrins by high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC/ESI/MS/MS) of 50 clinically suspected patients revealed one case of variegate porphyria and five cases of porphyria cutanea tarda. Plasma fluorescence scanning is a simple procedure that can be used as screening test to detect porphyria patients that require quantitation of urinary porphyrins as a second step. Quantitative determination of urinary porphyrins using HPLC/ESI/MS/MS and ion mapping techniques are applicable for the differential diagnosis of porphyria types, since each type has a characteristic porphyrins excretion profile. Quantitative determination of urinary porphyrins by HPLC/ESI/MS/MS used in this study is a modification for the method Stoev et al. while ion mapping technique is a new technique invented by the research team at the Biochemical Genetics Department

Genetic heterogeneity in spondylo-epimetaphyseal dysplasias: a clinical and radiological study

Introduction: Spondylo-epi-metaphyseal dysplasias (SEMD) are a heterogeneous group of skeletal disorders characterized by defective growth and modeling of the spine and long bones. Different types are described in the literature. Accurate classification of SEMDs is essential for proper genetic counseling. Patients and Methods: This study included 20 cases of SEMDs diagnosed by clinical and radiological findings. Cases were classified based on additional associated clinical and/or radiological features into 7 subtypes. Different subtypes were discussed with review of the literature. Results: The study illustrated the heterogeneity of SEMDs and emphasized the importance of detailed and meticulous clinical genetic and biochemical evaluation in addition to comprehensive radiological investigations for such group of disorders. It also recommends further molecular studies to identify the molecular bases of the different types. Keywords: Spondyloepimetaphyseal dysplasias, Genetic heterogeneity, Dyggve- Melchior-Clausen dysplasia, Glycoaminoglycans. Egypt. J. Hum. Genet Vol. 8 (2) 2007: pp. 147-17

Validation of the AASLD recommendations for Classification of Oesophageal Varices in Clinical Practice

Background & Aims The American Association for the Study of Liver Diseases recommends the use of a 2‐grade classification system (small and large) to describe the size of oesophageal varices (OV). Data on observer agreement (OA) on this system are currently lacking. We aimed to evaluate this classification and compare it to the widely used 3‐grade classification (grade 1 ‘small’, grade 2 ‘medium’, grade 3 ‘large’) among operators of variable experience. Methods High‐definition video recordings of 100 patients with cirrhosis were prospectively collected using standardised criteria. Nine observers of variable experience performed independent evaluations of the videos in random order. OV were scored using both systems. All assessments were repeated a year later by the same observers to assess intra‐observer agreement. Results Interobserver agreement (all observers) using the 2‐grade and the 3‐grade system was k = 0.71 (95% CI: 0.64‐0.78) and k = 0.73 (95% CI: 0.66‐0.79) respectively. When using the 2‐grade system, intra‐observer agreement between hepatologists (n = 3), luminal gastroenterologists (n = 3) and trainee gastroenterologists (n = 3) was k = 0.89 (95% CI: 0.86‐0.91), k = 0.72 (95% CI: 0.67‐0.77), and k = 0.74 (95% CI: 0.67‐0.8) respectively. With the 3‐grade system; intra‐observer agreement between the same three subgroups were k = 0.9 (95% CI: 0.87‐0.92), k = 0.73 (95% CI: 0.68‐0.78), k = 0.77 (95% CI: 0.71‐0.82) respectively. Conclusions There was no difference in OA between the 2‐grade and 3‐grade classification systems. Hepatologists had significantly higher levels of consistency in grading OV. This may have implications to create alternative training models for residents and fellows in the recognition and grading of OV

Prediction of survival among patients receiving transarterial chemoembolization for hepatocellular carcinoma: A response-based approach

Background and aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. Approach and results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. Conclusions: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognosticatio

ORIGINAL ARTICLES Detection of Urinary Organic Acids in high risk Egyptian Children by Electrospray Tandem Mass Spectrometry

ABSTRACT Establishing an approach for early diagnosis and monitoring of disorders associated with accumulation organic acids in high risk Egyptian children using liquid chromatography tandem mass spectrometry (LC/MS/MS). Organic acids were detected in urine using LC/MS/MS and results were then confirmed by gas chromatography/ mass spectrometry (GC/MS). For confirmation of the type of organic acidurias (OA), acylcarnitines and/ or amino acids profiles using LC/MS/MS were done to all patients showing abnormal organic acids profiles patterns. LC/MS/MS detection of urinary organic acids revealed 31 out of 50 subjects (62%) with 11 different OAs. Organic acids profile must be done to neonates admitted to critical care units suffering unexplained neurological manifestations. The LC/MS/MS is a fast and efficient technique for the detection of many organic acids in urine and can facilitate the future screening for OA among high risk Egyptian families

Evaluation of Strength of Different Resin Materials Used in Overdenture

Introduction: Finding a suitable material that could be used to restore relatively small inter-arch spaces in which reasonable aesthetics as well as good functional strength could be achieved is a difficult process that requires good understanding of the clinical situation and precise management. Historically Metal used to offer the smallest possible thickness with excellent strength but lacks resiliency with poor aesthetics. Aim of the study: This In-vitro study was conducted to compare two different aesthetic materials PEEK and ACETAL regarding their mechanical strength when used as Overdenture framework in a relatively small thickness. Material and Methods: 120 specimens were prepared according to the American Society for Testing and Materials (ASTM) International standards and divided into two main groups according to the material, group (A) PEEK samples and group (B) ACETAL samples. Each group of 60 specimens was subdivided into three different groups (I, II, III) according to three different thicknesses (1, 1.5 and 2 mm). Each group contains 20 identical samples, half of them were subjected to water absorption and the other half were left untouched. Then all specimens were loaded to failure in a Universal Testing Machine (UTM). Results: Data analyzed using Student’s t test for independent samples and showed that any increase in thickness lead to increase in the flexural strength which was proportioned in all Acetal samples in contrast to PEEK samples. All PEEK samples recorded significantly higher flexural strength values on every thickness than Acetal samples. Acetal samples with 2 mm of thickness did not offer enough strength as suggested by the international standards for polymer materials and ISO. Conclusions: The flexural strength of PEEK samples was 3 times higher than Acetal samples. Acetal thickness should be more than 2mm. water has a significant effect on the strength of Acetal material

Gravitational Search, Monkey and Krill Herd Swarm Algorithms for Phase Stability, Phase Equilibrium and Chemical Equilibrium Problems

<div><p>ABSTRACT</p><p>Phase equilibrium calculations (PEC) and phase stability (PS) analysis of reactive and non-reactive systems problems are important for the simulation and design of chemical engineering processes. These problems, which are challenging multi-variable and non-convex, require optimization techniques that are both efficient and effective in finding the solution. Stochastic global optimization algorithms, especially swarm algorithms, are promising tools for such problems. In this study, Monkey Algorithm (MA), Gravitational Search Algorithm (GSA) and Krill Herd Algorithm (KHA) were used to solve phase stability, phase equilibrium and chemical equilibrium problems. We have also studied the effect of adding a local optimizer at the end of the stochastic optimizer run. The results were compared to determine the strengths and weaknesses of each algorithm. When a local optimizer was used, MA was found to be a reliable algorithm in solving the problems. GSA had relatively the least numerical effort for all problems among the three algorithms but with low reliability. KHA was more reliable than other two algorithms without the use of a local optimizer. The performance of GSA, MA, and KHA was compared with Firefly Algorithm (FA) and Cuckoo Search (CS). In summary, this study found that CS algorithm was more reliable than the newly tested algorithms. Nevertheless, MA and GSA algorithms, when combined with a local optimizer, solve the thermodynamic problems as reliably and efficiently as CS.</p></div