Non HLA genetic markers association with type-1 diabetes mellitus

The currently available data identified IDDM1 and IDDM2 as 2 susceptibility loci for type 1 diabetes [T1D]. The major histocompatibility complex [MHC]/HLA region referred to as IDDM1 contains several 100 genes known to have a great influence on T1D risk. Within IDDM2, a minisatellite variable number of tandem repeats [VNTR] locus in the insulin gene [INS] promoter region is likely to represent the etiologic polymorphism. The aim of the present work was to study the association between genotypes and susceptibility to T1D among Egyptian diabetic children and their family members. Twenty-five nuclear Egyptian families with 27 children having T1D, aged 3-14 years, their nondiabetic 44 sibs, aged 3-15 years and their parents were included in our study. All studied children were subjected to: detailed history and family pedigree. Thorough clinical examination and anthropometric measurements. Laboratory work up of diabetes including random blood sugar [RBS] and HbA[1]C. Molecular genetics of INS was studied in four steps; nucleic acid purification, amplification, sequencing and haplotyping using flanking single nucleotide polymorphisms [SNPs] as surrogate markers for minisatellite alleles identification. Analysis of variant repeat distribution among Egyptian families combined with flanking haplotypes revealed that all our diabetic children had class I alleles of INS; 9 had class IC+, 9 had class ID+ and 9 had class ID-, while all non-diabetic family members had class III alleles of INS. Therefore the three class I alleles were considered to be equally predisposing to T1D, while class III alleles are dominantly protective. There was significant positive correlations between body mass index [BMI] and both HbA[1]C and AST liver enzyme among diabetic children with class IC+ but not other alleles; indicating that they need close monitoring of their diabetic control and liver functions beside following specific dietary regimens. It can be concluded that all class I alleles [IC+, ID+ and ID-] are equally important susceptibility factors for T1D among Egyptian children, while class III alleles [IIIA and IIIB] are dominantly protective. It is concluded also that our diabetic children with class IC+ are an especially endangered subgroup of diabetics. Genotyping for INS-VNTR alleles is recommended for diabetic children as an important step of diagnostic and follow up regimens and for their non-diabetic family members for family counseling and early identification of potential diabetics. Further studies of INS-VNTR alleles and HLA haplotypes all over Egypt are recommended to define the Egyptian susceptibility loci for T1D and their relations to the clinical and laboratory findings as an important national programs

Identification and supportive intervention programs of the problems of disabled children

According to International Classification of Diseases-Ninth Revision [ICD-9], neurodevelopmental disorders, asthma and physical disabilities are on the top of child disabilities .The aim of our study was to support families with disabled children and teach them how to deal with different difficulties. The present work was conducted on 85 disabled children [53 males and 32 females], aged 1-12 years allocated into 3 groups. Group 1 [neurodevelopmental group]: 45 patients subdivided into cases of cerebral palsy [CP], mental retardation [MR] and epilepsy [15 patients each].Group 2 [bronchial asthma] included 20 patients. Group 3 [physical disability] involved 20 diabetic children. All disabled children were subjected to thorough history taking, family pedigree, clinical examination and diagnostic investigations .The study was conducted in three steps. The first was a preparatory stage which lasted 6 months, an Initial three months of thorough training and evaluation of medical team and paramedical health providers was followed by an in formative and detailed pilot study which was conducted over the next 3 months .The second step lasted for 6 months and involved weekly visits and applying an in formative and standardized questionnaire to obtain their specific disability problems and to do a thorough family training to manage their problems. The third step [next 6 months]; involved bimonthly visits for assessment, reassessment and correction of the specific solutions taught to the parents. The most common problems encountered among cerebral palsy cases were high risk for injuries defective locomotor function, feeding difficulties and chronic constipation [100%, 73.3%, 40% and 33.3% respectively]. In mental retardation subgroup, the most common problems were delayed growth and development, defective family in formation and support for them and delayed socialization [100%, 73.3% and 46.7% in order]. Among cases of epilepsy we found high risk for injuries and inappropriate diets in 100%and inadequate self confidence in 40% of cases. In bronchial asthma group, most problems were related to: dealing with acute exacerbations [100%], indoor air [60%], molds [40%], and dust mites [35%]. While, among diabetic children, problems were related to insulin regimen and technique of injection, blood glucose monitoring, diet regimen and emotional support. The present work confirmed that well trained parents can improve the problems of their disabled children up to a satisfying extent .Feeding difficulties of CP improved in 66.6% and their defective locomotor function improved markedly in 6.7% and partially in 73.3%. Frequency and severity of bronchial asthma improved in 65%. Attitude of diabetics towards disease improved in 71.4%. Poverty, ignorance, non compliance of parents and presence of mixed types of disability were significant obstacles to our training programs. Hence; improvement of the surrounding environment will decrease the frequency and severity of many problems. Treatment of disabled children is a highly demanding task; it is not just a reflex prescription of medications for complications whenever they occur. Family counseling, team work [psychiatrists physiotherapists, pediatricians, etc.], good communications, improved family knowledge, well trained families and early intervention will ameliorate problems of disabled children. It is recommended to do our best to improve the quality of life of disabled children, to properly teach their parents how to deal with disabilities and to conduct research programs all over of Egypt to precisely establish the real problems and the optimal intervention programs for our disabled children

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