Egyptian Journal of Medical Human Genetics

Editorial Board

2012-02-01

Role of Gal and GalNAc containing glycans in various physiological processes

Muhammad Ramzan Manwar Hussain, Mukhtarul Hassan, Imran Afzal, Ayyaz Afzal — 2012-02-01

Abstract: Glycoconjugates are involved in the vital physiological functions including blood group determination, cancer recognition, protein stabilization, sperm-egg adhesion and pathogenic interaction in the body. These diverse biological functions of glycoconjugates are regulated by complex oligosaccharide structures linked with proteins and lipids in macromolecular assemblies. The diversity in oligosaccharide chains attached with lipids and proteins is specifically linked with the conformational behavior of sugar residues giving rise to unique carbohydrate structures with a wide range of sequence and anomeric linkages. This is a challenging task to explore the relationship between biological processes and stereochemical behavior of sugar residues. Current review article focuses the specific stereochemical involvement (anomery and linkages) of Gal and its derivative GalNAc in a wide range of cellular activities. These sugar residues exhibit different physiological functions at the terminal and subterminal positions in glycans.

Genetics of obesity

Rabah M. Shawky, Doaa I. Sadik — 2012-02-01

Abstract: There is now widespread recognition that the continuing increase in the prevalence of obesity seen in many countries is likely to have major adverse effects on public health. The National Center for Health Statistics reports that 61% of adults in the United States are overweight and 26% are obese. Also The National Health and Nutrition Examination Survey IV, 1999–2002, documents that 16% of children are overweight and 31% are at risk of becoming overweight or are already overweight, representing nearly a 300% increase since the 1960s. The genetic influences are likely to be particularly powerful in people with severe and early-onset obesity, the group is most likely to suffer adverse clinical consequences. In this review we will discuss the Genetics of body weight regulation including genes encoding factors regulating food/energy intake, genes encoding factors implicated in energy expenditure, and genes encoding factors implicated in adipogenesis as well as syndromic forms of obesity.

Molecular analysis of MECP2 gene in Egyptian patients with Rett syndrome

2012-02-01

Abstract: Rett syndrome (RTT) is a progressive neurodevelopmental disorder that affects mainly females comprising one of the most common causes of mental retardation in females. Mutations in the X-linked MECP2 gene have been identified to be the major cause for RTT. This study represents one of the limited MECP2 molecular analyses done on Egyptian patients with RTT, in which direct sequencing of MECP2 coding region in 10 female Egyptian patients provisionally diagnosed to have RTT was carried out. Four different pathogenic mutations were identified in four patients; three missense (C380T, C397T and C916T) and one nonsense (C382T). The four mutations, C→T transitions, were located in exon four. Patients with MECP2 mutation showed the clinical course of typical RTT. Analysis of X chromosome inactivation (XCI) pattern of genomic DNA in patients proved to be positive for MECP2 mutations identifying one patient with skewed inactivation pattern.

Phototherapy and DNA changes in full term neonates with hyperbilirubinemia

2012-02-01

Abstract: Background: Phototherapy has remained the standard therapeutic approach for neonatal hyperbilirubinemia. Oxidative effects of phototherapy on cell membranes and cell components may have a wide range of potential adverse effects, including enhanced lipid peroxidation and DNA damage. Apoptosis is an indispensable mechanism for maintaining many cellular functions, including cell replication, and removal of damaged cells with high burden of genetic mutations. Many genes function as apoptosis regulatory genes. Examples of these genes include the BCL2 gene which is an anti-apoptotic oncogene, and the BAX gene which acts as a promoter of apoptosis.Objectives: Assess the effect(s) of phototherapy on DNA and on the rate of apoptosis in full term neonates with hyperbilirubinemia. It comprised 35 neonates with indirect hyperbilirubinemia who received phototherapy for 48h, and 20 apparently healthy full term neonates with normal serum bilirubin level, as a control group. DNA damage was assessed by DNA fragmentation and micronucleus assay. Determination of the anti-apoptotic effect(s) of BCL2 gene was achieved by quantitative assay of its product, (BCL2) protein, by ELISA and BAX gene expression status was assessed by PCR.Results: The frequency of micronuclei in circulating lymphocytes of neonates who received phototherapy has significantly increased before and after phototherapy compared to controls, (p<0.001; p<0 0.00001), respectively. DNA fragmentation in circulating lymphocytes, was significantly higher among cases before and after phototherapy compared to controls (p<0.0001; p<0 0.00001). The plasma BCL2 protein was significantly lower in the cases before and after phototherapy compared to controls (p<0.01; p<0.01), respectively, and BAX gene expression was significantly high among cases before and after phototherapy compared to controls.Conclusions: Geno toxic effects of bilirubin and phototherapy, induce more DNA damage and enhances apoptosis of exposed cells, probably through down regulation of BCL2 expression and upregulation of BAX gene expression in neonates with hyperbilirubinemia.

Role of treadmill training versus suspension therapy on balance in children with Down syndrome

Gehan H. El-Meniawy, Hebatallah M. Kamal, Samah A. Elshemy — 2012-02-01

Abstract: Background and purpose: Maintaining balance is a subordinate but necessary requirement for most human actions. Most Down syndrome (DS) children, who constitute a large portion in our country, continue to evidence deficits in balance, co-ordination, and gait throughout childhood and adulthood. So, it is essential to seek an ideal physical therapy program to help in solving such a widespread problem. The present study was conducted to compare between the effect of treadmill training and suspension therapy on balance in children with DS.Subjects and methods: Thirty children born with DS from both sexes ranging in age from eight to ten years old were assigned into two groups of equal number. Study group I received treadmill training in addition to a designed exercises therapy program and study group II received suspension therapy in addition to the same exercises program given to the study group I. Stability indices were evaluated via using Biodex instrument system before and after three months of treatment.Results: The results revealed no significant difference when comparing the pre-treatment mean values of the two groups (study I and study II), while significant improvement was observed in all the measuring variables of the two groups when comparing their pre and post treatment mean values. Significant difference was also observed when comparing the post treatment results of the two groups in favor of the study group II.Conclusion: Suspension therapy for children with DS is an excellent supplement to regularly scheduled physical therapy intervention for the purpose of improving the degree of stability in those patients.

Profile of genetic disorders prevalent in northeast region of Cairo, Egypt

Rabah M. Shawky, Nermine S. Elsayed, Doaa S. Ibrahim, Neveen S. Seifeldin — 2012-02-01

Abstract: As clinical geneticists, we recently reviewed our 43years experience in an attempt to represent the frequency of genetic disorders in the Division of Genetics at Pediatric Hospital, Faculty of Medicine, Ain-Shams University, Cairo, Egypt, during the period from 1966 to 2009.All patients (from birth up to 18years) suspected of having a genetic disorder were referred to the Genetics Clinic in the same hospital. 28,689 Patients were proved to have genetic disorders after full investigations among 660,280 children attending the Pediatrics Hospital which constituted 4.35% or 43.5/1000. Neurologic disorders were the most common (31.38%) followed by hematologic disorders (18.48%), chromosomal abnormalities (11.51%), fetal, neonatal and infant deaths (6.56%), special senses (5.82%), inborn errors of metabolism (4.24%), endocrine disorders (3.87%), skeletal disorders (3.17%), genito-gonadal anomalies (3.10%), neuromuscular disorders (2.86%), syndromes (2.08%), genodermatoses (1.92%), cardiac disorders (1.47%), gastrointestinal tract anomalies (1.37%), renal anomalies (0.26%), connective tissue disorders (0.26%), respiratory defects (0.22%), vascular anomalies (0.21%), and immunologic disorders were the least common (0.19%).Our study showed a high prevalence of genetic diseases among Egyptians which are nearly the same in the other studies in Egypt and are rapidly becoming a major public health concern. Establishment of national or hospital based registers for genetic disorders is very important to know the magnitude of the problem so that the national program for the prevention of genetic disorders can be implemented.

Modulation of back geometry in children with spastic diplegic cerebral palsy via hippotherapy training

Gehan H. El-Meniawy, Nahed S. Thabet — 2012-02-01

Abstract: Background and purpose: Controlled hippotherapy environment provides a foundation for improved neurologic function and sensory processing. This foundation can be generalized to a wide range of daily activities, making the horse a valuable therapeutic tool for rehabilitation. The purpose of this study was to examine the effects of a once weekly, twelve-week hippotherapy program on back geometry in children with spastic diplegic cerebral palsy.Subjects: Thirty spastic diplegic children from both sexes, ranging in age from six to eight years represented the sample of this study. The degree of spasticity ranged from 1 to 1+ according to the modified Ashworth scale. They were divided randomly into two groups of equal number A (control) and B (Study).Procedures: Evaluation of back geometry parameters was conducted for each child of the two groups before and after three months of treatment via using Formetric instrument system. Group A received a designed exercise program, while group B received hippotherapy training in addition to the same exercise program given to group A.Results: No significant difference was noticed when comparing the pre-treatment results of the two groups, while significant improvement was observed in all the measuring variables of the two groups when comparing their pre and post-treatment mean values. Significant difference was also observed when comparing the post-treatment results of the two groups in favor of group B.Discussion and conclusion: Hippotherapy utilizes the movement of the horse to provide sensory feedback and may be used as a therapeutic intervention for improving back geometry in children with spastic diplegia.

Serum amino acid abnormalities in pediatric patients with chronic renal failure with and without history of thromboembolic manifestations

2012-02-01

Abstract: Background: Plasma amino acid concentrations have been reported to be abnormal in patients with chronic renal failure. l-Arginine has been used to improve endothelial function by increasing nitric oxide (NO) bioavailability.The present study aim at investigating the status of plasma amino acids in pediatric patients with chronic renal failure (CRF) on regular hemodialysis (HD) with and without history of thromboembolic manifestations.Methods: The study included 21 hemodialysis patients subdivided into two groups (those with no history of thromboembolic manifestations and those with positive history of thromboembolic manifestations) The control group included 13 age and sex matched apparently healthy subjects, After careful history taking, clinical examination, the following laboratory investigations were performed: serum calcium, phosphate, albumin, and creatinine (for controls only), complete blood count (CBC) and serum amino acid analysis.Results: HD patients had a significantly lower concentration of threonine, valine, methionine, leucine, tyrosine, phenylalanine and tryptophane than the control group (p=0.032, 0.020, 0.046, 0.011, 0.000, 0.022, and 0.004 respectively). There was no significant difference between HD patients and the control group as regard aspartic acid, serine, asparagine, glutamic acid, proline, glycine, alanine, cystine, isoleucine, lysine, histidine, and arginine. The mean serum l-arginine level was lower in 61.9% of HD patients than the mean of the controls with no significant difference. l-Arginine concentration was not significantly different between HD patients with and without history of thromboembolic manifestations.Conclusion: Several abnormalities in amino acids were present in HD patients compared to controls. The mean serum l-arginine level was lower in 61.9% of HD patients than the mean of the controls with no significant difference. l-Arginine concentration was not significantly different between HD patients with and without history of thromboembolic manifestations. HD patients without history of thromboembolic manifestations had significantly lower glutamic acid concentrations and significantly higher phenylalanine concentrations than HD patients with history of thromboembolic manifestations.

Role of ascitic fluid C3 in spontaneous bacterial peritonitis

Amany Talaat Kamal, Eman Nagib Osman, Rasha Youssef Shahin — 2012-02-01

Abstract: Background: The C3 component of complement tends to be reduced in cirrhosis and patients with reduced ascitic fluid C3 concentration and reduced opsonic activities have been shown to be predisposed to SBP .Aim of the work: To compare the level of ascitic fluid C3 concentration in cirrhotic patients with and without spontaneous bacterial peritonitis to determine its possible protective role against acquiring infection.Methods: This is a prospective case-control study in which we recruited 45 cirrhotic patients presenting with ascites, of which 25 showed evidence of SBP. All patients had diagnostic paracentesis, received the appropriate treatment, discharged and followed-up monthly for 3months, with ascitic fluid C3 measurement. Ascitic fluid C3 was compared between both groups at baseline and for three successive reading over 3months. It was also compared in the same patients group over this interval and correlated with other AF parameters at baseline reading.Conclusion: Ascitic fluid C3 is reduced in cirrhotic patients with SBP and stays lower compared with those without the infection after the first episode. So we conclude that C3 plays an important role in the local defense of ascitic fluid and needs further long term follow-up studies to evaluate its role as a predictor of prognosis for cirrhotic ascitic patients.

Pilot study for assessment of prevalence of intrafamilial hepatitis C transmission in relation to salivary viral load among infected patients with and without chronic renal failure

2012-02-01

Abstract: HCV-RNA in saliva of HCV patients provides a biological basis for its potential transmission. HCV viremia is particularly high in HCV patients on hemodialysis. This study aimed to evaluate the prevalence of HCV in saliva of HCV patients with and without renal failure, and the possible role of intrafamilial transmission of the virus.Twenty HCV patients were enrolled in this study. They were divided into two groups: 10 HCV-infected patients without renal failure (Group I) and 10 with renal failure (Group II). Detection of HCV-RNA by quantitative RT-PCR in serum and saliva of both groups was done. Thirty-eight family members of both groups were included for the detection of serum HCV antibody. The percentage of the saliva-positive patients for HCV was significantly higher in the renal failure group (70%) than the other group (40%) (p<0.05). There was insignificant statistical difference between the two groups as regards infectivity to their family contacts.Also there was insignificant correlation between the level of viremia and the intra familial transmission with a mean+SD (9,33,250+24,501) in negative relatives and a mean+SD(79,912+26,879) in positive relatives (p>0.05). But a significant correlation was revealed between the level of viremia and saliva positivity, with a mean+SD(12,95,666+1792) in saliva-positive patients and a mean+SD (3,74,465+2150) in saliva-negative patients (p<0.05). There was a highly significant difference between infectivity of HCV saliva-positive patients and saliva-negative patients to their family contacts (p<0.001).Conclusion: Increased percentage of HCV detection in saliva of HCV patients with renal failure on HD may cause spreading of HCV in HD units among RF patients. Also there was increased percentage of interfamilial infectivity among the saliva-positive patients to their relatives and this suggests that saliva might have an infective role.

Haemophilia A patients are not at increased risk of hepatitis A virus infection: An Egyptian experience

2012-02-01

Abstract: Background: Hepatitis A virus (HAV) infection is endemic in Egypt. Haemophiliacs are at risk of transmission through exposure to blood products. We evaluated the seroprevalence of hepatitis A in Egyptian patients with haemophilia A as well as the safety and immunogenicity of subcutaneous hepatitis A vaccine in haemophiliacs.Methods: 182 male children and adolescents were studied (82 patients with moderate and severe haemophilia A and 100 healthy controls). Screening for anti-HAV antibody was done and seronegative subjects received hepatitis A vaccine (Havrix™) at a dose of 720 Elisa Units at 0 and 6months, given subcutaneously in haemophiliacs and intramuscularly for controls. Seroconversion was assessed 2months after the second vaccine dose by anti-HAV IgG.Results: Seroprevalence of HAV antibodies was 87.6% among haemophiliacs and 90% among the control group. Seronegative children (mean age 4.4±3.71years) were significantly younger than seropositive children (mean age 10.2±3.86years). Hepatitis A vaccine was given to 10 non immune haemophilia patients and 10 controls. The vaccine was well tolerated with local side effects including pain in 40% and erythema in 20% of haemophiliacs versus 20% for pain and erythema in the control group. All patients and controls developed seroconversion 2months after the second dose; with no significant difference as regards the titre of anti-HAV IgG (351.4±65.0IU/L for haemophiliacs and 367.0±132.3IU/L for controls).Conclusion: HAV infection occurs early in life in Egyptian children, necessitating hepatitis A vaccination in early life. The vaccine is safe and effective when given subcutaneous in haemophiliacs

Hospital-acquired pneumonia in critically ill children: Incidence, risk factors, outcome and diagnosis with insight on the novel diagnostic technique of multiplex polymerase chain reaction

Mervat Gamal Eldin Mansour, Sherin Bendary — 2012-02-01

Abstract: Hospital-acquired pneumonia (HAP) is the most frequent hospital-acquired infection in critically ill patients. National Nosocomial Infections Surveillance (NNIS) system reported that HAP accounts for as much as 31% of all nosocomial infections acquired in medical intensive care units (ICU). The increasing incidence of infections caused by antibiotic-resistant pathogens contributes to a high mortality rate, longer ICU stay and higher costs. In this study, we aimed to identify the incidence of HAP, the associated risk factors, and its effect on outcome. We evaluated as well the usefulness of multiplex polymerase chain reaction (m-PCR) as a novel tool for emergency diagnosis of HAP.We examined all consecutive admissions to Pediatric ICU from February 2010 to August 2010. Patients were diagnosed to have HAP when their Clinical Pulmonary Infection Score (CPIS) index was more than 6. Blood and endotracheal aspirate (ETA) were tested for bacterial pathogens by microbiological cultures and multiplex PCR simultaneously for all enrolled patients.Twenty-five patients out of 90 admissions (27.7%) developed HAP during the observation period, with incidence rate of 13 per 1000 patient-days and overall mortality of 56%. Gastro-esophageal reflux disease (GERD), mechanical ventilation (MV), endotracheal re-intubation and sedation were the main recorded risk factors for HAP. ETA had better diagnostic yield than blood specimens for the diagnosis of HAP. Multiplex-PCR showed better sensitivity and positive predictive value than bacterial culture for etiological diagnosis of HAP. Acinetobacter and Klebsiella pneumoniae were the most common identified pathogens. In conclusion, hospital-acquired pneumonia adversely affects patients outcome in our setting, for which we should manipulate the identified modifiable risk factors. Moreover, m-PCR permits simultaneous detection of several bacterial pathogens in a single reaction which can optimize the emergency diagnosis of HAP and can improve etiology-directed clinical management of bacterial pneumonia.

Multiple pterygium syndrome with marked pterygia of the fingers and MRI changes in the spine

Rabah M. Shawky, Solaf Elsayed, Nagwa Gaboon — 2012-02-01

Abstract: We report a two years old Egyptian girl, the first birth of consanguineous marriage with clinical findings consistent with the diagnosis of the autosomal recessive multiple pterygium syndrome (Escobar) (growth retardation, craniofacial dysmorphism, multiple pterygia, kyphoscoliosis, multiple joint contractures especially affecting the lower limbs). What characterizes out patient was the extensive pterygia of the fingers which kept them permanently flexed, while they were very mild in the neck, axillary folds and knee joints.Our patient suffered also from mental retardation although mentality is commonly reported to be normal in this syndrome. MRI of the spine revealed widened spinal canal and engorged intraspinal vessels, which were not reported before.

Trigonocephaly and Dandy walker variant in an Egyptian child – Probable mild Opitz trigonocephaly C syndrome

Rabah M. Shawky, Heba Salah Abd-Elkhalek — 2012-02-01

Abstract: We report a one year old male patient with slight upward slanting palpebral fissures, hypotelorism, bulbous nose, high arched narrow palate, low set ears, bilateral partial simian creases, short neck with loose skin over it, thick ridge over the metopic suture giving a trigonocephaly, brachycephaly shape to the skull, hypoplastic scrotum and bilateral undescended testes, and mild generalised hypotonia. Although most of the reported cases suffered from severe mental retardation, our patient had mild mental retardation. CT of the brain demonstrated Dandy walker variant and trigonocephaly. To our knowledge this anomaly was reported once before with Opitz trigonocephaly C syndrome (OTCS). We consider our patient as a mild form of OTCS and he needs close follow up because over time there may be a developmental delay, severe mental retardation and seizures.

Educational Corner

Mohammad Saad Zaghloul Salem — 2012-02-01

All life activities in living cells, whether on a molecular level like ATP production, a cellular level like cell division, a tissue level like muscle contraction or on a whole organ level like hearing for instance, are mediated via a very large number of inter-related metabolic networks. A metabolic network is defined as a cascade of controlled biochemical reactions and biophysical alterations that transform one, or more, substrate to one, or more, products. In human cells, nearly 4100 (four thousand and one hundred) of these networks have been delineated () .