Profile of Egyptian patients with mucopolysaccharidosis

Mucopolysaccharidoses [MPS] are chronic progressive lysosomal disorders [Six distinct types] which are inherited as autosomal recessive except MPS II which is inherited as X-linked recessive disorder This study is designed to investigate a group of Egyptian patients with MPS biochemically using screening test by electrophoretic separation of glycosaminoglycans and enzymatic assay in order to establish the diagnosis of the disorder and its subtypes, to prepare patients for enzyme replacement therapy. Also this will help in proper genetic counseling and prenatal diagnosis. Establishing a reliable rapid screening test for MPS is another aim of the study. The present study included 20 index cases suspected clinically as mucopolysaccardioses at the Medical Genetics Center, Ain Shams University [ASUMGC].They were subjected to full history taking, thorough clinical examination, family pedigree construction, skeletal survey, abdominal ultrasound and echocardiography, quatitative assay of glycosaminoglycans [GAGs] by diemethylmethlene blue [DMB] is done. The level of urinary GAGs by two dimentional electrophoresis [DMB] test was high in all patients tested. After that the patients were subjected to 2-DEP to determine the pattern of GAGs for probable type of MPS. 11 cases [55%] showed big dermatan sulfate spot [Type I, II or VI]. Seven cases [35%] showed hepran sulfate spot [Type III], 2 cases [10%] showed keratan sulfate spot [Type IV]. Finally patients were subjected to enzyme analysis specific for each type of MPS to confirm diagnosis. Reaching a specific diagnosis is of importance for genetic counseling and prenatal diognosis which is possible for all types of MPS. Prenatal diagnosis was done by 2-DEP of the amniotic fluid for four mothers of affected patients of MPS. One fetus was proved to be affected with MPS III. Another fetus was affected with MPSII. The others fetuses were normal

Study of amino acid disorders among a high risk group of Egyptian infants and children

The present work aimed at investigating infants [in neonatal and post neonatal period] and children suspected of having inborn errors of metabolism with unexplained mental retardation. The frequency pattern of the various amino acid disorders, in a group of selected infants and children was done to document the prevalence of various amino acid disorders among Egyptian children. In this study, recent methods to investigate such disorders have been carried out by amino acid analyzer which detects levels of amino acids. Extended metabolic screen which also detects amino acid disorders, organic acid disorders and the defects of fatty acid oxidation has been carried out. These recent methods have therefore the potential of yielding information on the physiological and pathophysiological status of different metabolic pathways, as well as their interrelationship. The total number of cases attending the outpatient clinic during the period of study were 1343 index cases, among them 50 index cases [3.72%] were suspected of having inborn errors of amino acid and, 20 cases [40%] of them have confirmed positive inborn errors of amino acid metabolism. Concerning the confirmed 20 cases, their ages ranged from 5 days to 11 years with a mean of 54.75 +/- 33.09 months with equally sex distribution. The overall consanguinity rate recorded was 65%, while the family history of the similarly affected cases was 30%. The main clinical findings included mental retardation 85%, convulsions 40%, and hypo pigmentation 75%, microcephally 15%. Associated anomalies were present in 35% of cases. Among them eye anomalies were the most common [8%]. The prevalence of aminoacidopathies during the period of the study was 1.5% [of 20 studied cases], among them PKU was found to be the commonest aminoacidopathies 1.11%, while the remaining diagnosed cases representing 0.07% for each

Differential expression of E-cadherin in ductal and lobular breast carcinomas and its biologic and diagnostic value

E-cadherin is a calcium dependent epithelial cell adhesion molecule. Loss of E-cadherin function has been associated with aggressive behavior in various malignancies. In this study, we analyzed the pattern of E-cadherin expression in 25 invasive carcinomas [15 ductal and 10 lobular] and 14 in slat carcinomas [10 ductal and 4 lobular] to determine its role in the morphogenesis of breast carcinoma. E-cadherin was Semiquantitatively evaluated on paraffin-embedded tumor tissue by immunohistochemistry. Our results proved a highly significant correlation of E-cadherin membrane expression with the histologic phenotype of the tumor. While preserved [strong] to reduced membrane expression was seen in all invasive and in situ ductal carcinomas as in normal mammary epithelium, 90% [9/10] of invasive lobular carcinoma [ILC] and 75% [3/4] of lobular carcinoma in situ [LCIS] cases showed complete loss of E-cadherin expression. The only E-cadherin positive ILC case was diagnosed histologically as pleomorphic variant and was associated with solid ductal carcinoma in situ [DCIS] component. This tumor most probably represents an example of invasive ductal carcinoma [IDC]. Reduced E-cadherin expression increased significantly from DCIS [20%] to IDC [66.7%]. A highly significant difference between E-cadherin expression in IDC and ILC [P = 0.0001] and a significant difference between DCIS and LCIS [P = 0.004] were found. So we concluded that in tumors with histologically equivocal features, immunohistochemical detection of E-cadherin expression can be a useful diagnostic tool for differentiation of the ductal and lobular carcinomas of the breast