Genetic study in children with mental retardation

Mental retardation with both genetic and environmental causes affects about 3% of the population. Etiology cannot be determined in at least 30-50% of cases. The aim of this study was to identify the percentage of minor chromosomal abnormalities in the children with probably genetic mental retardation. Twenty two children, 13 males and 9 females aged 2.5 to 12 years [6.25 +/- 1.34] with mental retardation attending the genetic outpatient clinic; Minoufiya university hospitals and Medical Genetics Center; Ain Shams University; were studied, in the period from August 2004 to December 2006. Children with IQ less than 70 and had at least one of the following additional criteria: prenatal or postnatal growth retardation, dysmorphic facial features, multiple congenital anomalies or neuropsychiatric abnormalities were included in this study. All studied children were subjected to: detailed history and three generation family pedigree, thorough clinical examination, anthropometric measuremants, lQ assessment by Wechsler-revised scale, visual and audiological assessment and imaging studies including brain CT, pelvi-abdominal ultrasonography, and echocardiography when needed. Plasma and urine amino grams and cyto genetic evaluation including routine conventional karyotyping using G-banding technique and chromosome elongation study by synchronization using MTX, FUDR and thymidine release. The degree of mental retardation was assessed according to WHO classification and DSM-IV criteria, 63.6% of then had mild MR, 27.2% had moderate MR and 4.5% had severe MR. The pedigree analysis of studied cases revealed positive consanguinity in 5 cases [22.7%] [1st cousin marriage] and positive family history of mental retardation in 2 cases [9.1%], and maternal history of miscarriages in 7 cases [31.8%]. As regard clinical presentation of studied cases, 13 cases [59%] presented with developmental delay, 6 cases [2 7.3%] presented with dysmorphic facial features and 3 cases [13.6%] presented with epilepsy. Clinical data revealed that, 41% had short stature, 72.7% had dysmorphic facial features, 4.5% had congenital heart disease, 41% had hand and foot anomalies and 45.4% had neurological abnormalities. Accurate conventional cyto genetic study within 450 band resolution [G-banding] revealed that nineteen cases [86.3%] of the studied cases had normal karyotypes and three cases [13.7%] showed the following chromosomal abnormalities: 45 XY, t [13, 14], 46 XX, del [5] and 47 XX,+mar. Chromosome elongation techniques [more than 550 bands]; confirmed these informations. It can be concluded that: chromosomal abnormalities could be one of the etiological causes of mental retardation; accurate conventional cyto genetic study still has its important role in their diagnosis and that chromosome elongation and high resolution chromosome analyses may have a complementary role and should be reserved for diagnosis of undetected cases by conventional cyto genetic studies

Bone mineral density and vitamin d receptor polymorphism in beta-thalassemia major

Osteoporosis is the most prevalent bone complication in beta-thalassemic patients despite regular transfusions and iron chelation therapy. Although its etiology is multi-factorial, genetic factors play an important role in pathogenesis. These factors have not yet been clearly defined, however, osteoporosis may be related to vitamin D receptor gene BsmI polymorphism. In this study, BsmI vitamin D receptor gene polymorphism was analyzed using polymerase chain reaction and BsmI restriction fragment length polymorphism in 42 regularly treated- beta-thalassemic patients of different ages. Bone mineral density was measured by peripheral quantitative ultrasound at the heel of the foot. Serum levels of alkaline phosphatase, calcium, phosphorus, ferritin and 25-hydroxyvitamin D[3] were determined. Patients were divided into two groups according to pubertal signs: group I [22 children], and group II [20 adolescents and adults]. The Z-scores of bone mineral density in both groups were -1.32 +/- -0.9 and -2.30 +/- -1.02 respectively, with a significant difference between the two groups. The height standard deviation and 25-hydroxyvitamin D[3] were significantly decreased in group II compared to group I. Moreover, significantly lower bone mineral density and height standard deviation were detected among patients with BB vitamin D receptor genotype. Therefore, this genotype may be considered as a risk factor for osteoporosis in p-thalassemic patients

Neonatal screening of the common endocrine and metabolic disorders in Menoufiya governorate

Hereditary diseases and congenital marformations have been reported to affect 2-5% of all live births; they account for up to 30% of pediatric hospital admissions, and cause about half of childhood deaths in developed countries. Available evidence suggests that genetic are important also in countries of the Eastern Mediterranean Region. The following factors may contribute to the prevalence of genetically determined disorders: the high consanguinity rates; the trend of continuing to bear children up to menopause; the general lack of public awareness about genetic diseases and the dearth of genetic services in the region. Neonatal screening tests early detect disorders in newborns for which interventions shortly after birth have obvious benefits. We aimed at screening of congenital hypothyroidism [CH], phenylketonuria [PKU], and galactosemia which are common causes of preventable mental retardation and starting their early intervention. Our study included 15.000 dried blood specimens [DBSs] from the newborns of all the ten conters of the Menoufiya governorate, as a representative random sample of the year 2007. all speciemens were analysed in neonatal screening laboratory in our genetics and endocrinology unit, pediatric department; Menoufiya University in collaboration with the central laboratories of ministry of health and population; using ELISA for TSH analysis and flourometric assay [WALLAC system, Perkin Elmer] for PKU and galactosemia screening. Preservation and transfer of DBSs were according to the recommendations of the International Society for Neonatal Screening. Because of the high costs, we randomly selected two thousands DBSs for PKU screening and another two thousands for screening of galactosemia. Out of the /5,000 DBSs, 99.84% were negative for CH [TSH < 20 ulU/ml]. Twenty five cases were borderline for CH, while 9 cases only were confirmed as CH after clinical examination and revaluation using serum samples [serum TSH > 20 ulU/ml and T4 < 0.8 ng/dl], the confirmed cases were treated according to the management schedule. So the incidence of CH in our study was 0.06%. As regards PKU screening; 93.95% of studied samples were negative [phenyl alanine < 2.1 mg/dl]. Only 21 cases were initially borderline for PKU [phenyl alanine = 2.1-3.0 mg/dl, while clinically normal] but no PKU cases were detected after revaluation. On the other side; the 2000 DBSs screened for galactosemia were negative [Galactose uridyl -1 transferase enzyme [GALT] > 3.5 u/gHb]. On conclusion, because of the high costs of mass screening for PKU and galactosemia, only screening of high risk families and neonates is recommended. On the other hand screening programs should include our more common problems as congenital deafness and hemoglobinopathies

Pervalence of clinically significant neonatal jaundice and its relation to some risk factors in Minoufyia governorate

Hyperbilirubinemia is one of the most common problems encountered in newborns. Nowadays it was noticed to be seen more than before, representing an important medical, social, and economic health problem. A number of epidemiologic factors may exert their influence on increasing the occurrence of neonatal jaundice. To estimate the prevalence of neonatal jaundice in Minoufyia governorate using the judgment of Integrated Management of Childhood Illness [IMCI] project for the detection of clinically significant jaundice and to identify some of its risk factors with spotting light on the role of family physician in the management. This study was carried out on 300 fullterm and preterm neonates [153 males, and 147 females], selected from three hospitals and two Maternal and Child Health Centers in Shebin El Kom City and districts. The study design composed of two main parts: A cross sectional study [200 cases], to estimate the prevalence of jaundice among neonates [group I], and: A case control study [100 cases], to identify the important risk factors for occurrence of neonatal jaundice [group IIA, B]. The prevalence of clinically significant neonatal jaundice was 17%. Some neonatal risk factors were found to be significantly increased among jaundiced babies compared to controls: low birth weight, prematurity, and infection [P values 0.02, 0.01, and 0.001 respectively]. However in comparing, sex, breast feeding, cephalhematoma, the difference was found to be insignificant. As regard maternal factors, the use of oxytocin during first stage of labor, was the only significant risk factor [P value 0.01], however, maternal age, education, consanguinity, jaundice of previous sibling, intake of iron and tonics, abdominal ultrasound, and mode of delivery were insignificant factors. The most common cause of pathological jaundice was infection, and the most commonly used treatment was phototherapy. More cases were referred from primary health physicians [PHP] compared to specialists with a significantly earlier age at referral [3.7+ 0.21 days in cases referred from PHP and 5.45 + 0.31 days in those of specialists]. However the outcome of cases didn't differ significantly between cases referred from PHP compared to specialists. The prevalence of neonatal jaundice is high in Minoufyia. A significant relation was found between the occurrence of neonatal jaundice and some maternal and neonatal risk factors which need to be reevaluated on a larger scale. The clinical criteria of the IMCI project for diagnosis and referral of jaundiced newborn are very beneficial and need to be generalized and supported by a scheduled neonatal follow up early after birth

Comparative study of peripheral intravenous cannulae versus peripherally inserted central venous catheters in newborn infants

Newborn infants especially the high-risk groups require venous access for total or partial parenteral nutrition, intravenous fluids and medications for prolonged periods of time. The aim of this study was to compare between the complications of peripheral intravenous cannulae [nosocomial infection, local complications and mechanical complications] versus peripherally inserted centrally placed catheters in neonates. The present study was carried out on 50 neonates admitted to the Neonatal Intensive Care Unit [NICU] of Minoufiya University Hospital from June 2002 to June 2003 and expected to require venous access for at least 7 days for intravenous [IV] fluids, IV antibiotics, IV medications or parenteral nutrition. All infants were assigned randomly on admission to use either peripheral intravenous [PIV] cannula [n=25] referred to as [PIV group] or peripherally inserted central [PICC] catheters [n=25] referred to as [PICC group]. We found that there was a significant difference between both groups as regard number of attempts of insertion required for total IV therapy [2.36 +/- 1.07 in PICC group versus 11.48 +/- 5.72 in PIV group P<0.001]. The mean number of catheters used was significantly lower with PICC group than PIV group [1.08 +/- 0.27 in PICC group versus 6.52 +/- 3.77 in PIV group P<0.001]. Episodes of proven sepsis in PICC group were found to be significantly lower than in PIV group [5 cases [20%] in PICC group versus 12 cases [48%] in P/V group P<0.05]. The average time to develop sepsis [infection free catheter days] in PICC group was significantly higher than that in Ply group [5.67 +/- 3.13 in PICC group versus 2.83 +/- 1.03 in PIV group P<0.001]. The mechanical complication was statistically significantly lower in the PICC group than that in the PIV group. The rates of phlebitis and catheter associated infection are lower in the PICC group than the PIV group. Apart from the high cost, PICC is a desirable intravascular device in newborn with difficult venous access and in those requiring prolonged antibiotics or fluid therapy

Seroprevalence of Helicobacter pylori infection among healthy children in Minoufyia governorate

Helicobacter Pylori [H. Pylori] infection has a wide spread distribution, but the prevalence varies between developed and developing countries. This variability in prevalence rate can be explained by the difference in socioeconomic status. To determine the seroprevalence of Helicobacter Pylori infection among apparently healthy infants and children living in Minoufyia governorate and belonging to various social classes, also to assess the local risk factors influencing the prevalence of H. Pylori infection. This study was carried out on 300 apparently healthy infants and children [176 male, 124 female] attending primary health care centers and basic schools in Minoufyia govemorate. Cases were subjected to history sheet, and thorough clinical examination to exclude any systemic disease. Serum samples were taken and assayed for the presence of Anti-Helicobacter Pylori antibody [IgG] measured by Enzyme Linked Immunsorbant Microassay test [ELISA]. The overall H. Pylori seroprevalence in cases of the study were 51% [153/300] and frequency of seropositive cases increased highly significantly with advance of age. On studying risk factors for acquisition of H. Pylori infection in our cases, we found a significant difference between seropositive and seronegative cases regarding [socioeconomic status, family income, breastfeeding, educational arid occupational status of parents and cases who had not owned domestic animals]. On the other hand, we found non-significant difference between seropositive and seronegative cases concerning [Sex, water supply, and family history of gastric troubles]. Prevalence was significantly higher among cases of farmers compared to those of blue collar and white-collar workers. Moreover cases living in white-collar families had a lower risk of being positive for H. Pylori infection. Studying dietary factors, we found that high salty food, low fruits and low milk intake were risk factors while there was no significant difference regarding [high vegetables, fish, chicken, been, rice and cheese] intake. In a trial to study effect of H. Pylori on growth, we found only a significant difference in height between infected and non-infected children in those cases older than 8 years up to 13 years compared to the other two age groups. Moreover, no significant difference in the centile value for weight was detected between infected and non-infected cases among the three age groups. Helicobacter Pylori is acquired in early childhood and there's gradual Seroconversion [cumulative- seroconversion], as the prevalence increased with age. Prevalence of H. pylori infection in Minoufiya is high, and there were many risk factors influencing the prevalence of H. Pylori infection in children, however other factors requiring wider scale studies for confirmation