Prenatal genetic testing, counseling and follow-up of 33 Egyptian pregnant females with history of mucopolysaccharidoses

Mucopolysaccharidoses [MPS] are autosomal recessive disorders characterized by deficiency of lysosomal enzymes which break down the glycosaminoglycans [GAGs] which results in widespread intra and extra-cellular accumulations of GAGs. Early initiation of treatment, before the onset of irreversible tissue damage, clearly provides a favorable disease outcome. Early detection might be afforded by analysis of amniotic fluid. To report our experience of prenatal diagnosis of MPS over 14-year period for cases referred from medical centers throughout Egypt. Also to report the benefit of prenatal genetic testing in cases accompanied with genetic disorders. The present study included 33 pregnant women at risk of having a fetus with MPS. Of these cases, 3 women had more than one pregnancy evaluated. All cases had a detailed genetic ultrasound examination and a maternal serum alpha-fetoprotein [MSAFP] evaluation during the second trimester of pregnancy. Thirty-eight amniocentesis procedures were performed during the study for 2 dimensional electrophoresis [2-DEP] of GAGs. Positive consanguinity was present in near 70% [23/33] of the couples. Detailed genetic ultrasound examination revealed a case with anencephaly and another one with a twin pregnancy One case had a MSAFP of 3.6 multiple of the normal median [open neural tube defect]. Another 2 cases had a risk of having Down syndrome. Results of the 2-DEP of GAGs in amniotic fluid revealed 36.8% [14/33] affected fetuses. During the final counseling setting of the 14 cases with abnormal results, 43% [6/14] elected to continue their pregnancy while 57% [8/14] elected termination. Early prenatal screening and diagnosis, through a systematic multidisciplinary approach, to all cases of mucopolysaccharidoses are recommended, to improve the quality of life and to avoid the presence of other associated fetal developmental malformations

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

Prevalence of some lipidosis among Egyptian children with neurodegenerative disorders

The present work comprised 30 patients belonging to 27 families. The age of the studied patients ranged from 7 months to 10 years [mean 43.9 +/- 27.69 months]. The age of onset of the disease ranged from 7 months to 5 years [mean 17.26 +/- 13.3 months]. All patients suffered from developmental delay or progressive loss of previously acquired milestones, with no coarse facial features, organomegaly or ectodermal abnormality. For all patients the following was done: - Full medical history, thorough clinical examination and family pedigree construction. - Fundus examination and nerve conduction velocity [NCV]. - MRI of brain and IQ assessment. - Measurement of arylsulphatase A, galactocerebroside: beta-galactosidase activity in peripheral leucocyte was also done together with chitotriosidase level in plasma. Twenty two patients [73.33%] had normal fundus examination, and eight patients [26.66%] had various fundus findings [three patients [10%] had pale optic disc, and five patients [16.66%] had optic atrophy] - Twenty five patients [83.33%] had normal NCV, and five patients [16.66%] had demyelination. - All patients had +ve MRI findings, 19 patients [63.33%] had dysmyelination and 11 patients [36.33%] had brain atrophy. - Twenty six patients had normal value of Aryl sulphatase A activity [ASA] [51-200 micro mol/g- p/h], while three cases demonstrated decreased activity [one case had pseudodeficiency value [10-50 micro mol/g-p/h], and two cases had actual deficiency of enzyme activity [<10 micro mol/g -p/h] and diagnosed as metachromatic leukodystrophy]. - Twenty eight patients had normal value of Chitotriosidase activity [CT] [4-80 micro mol/l/h] and one patient had high value. - Galactocerebroside beta-galactosidase activity [GALC] was measured in leukocytes for 29 index cases. Normal value was detected in all cases [0.5-4 micro mol/g-p/h]. One case [3.33%] had Gaucher disease, another had aryl sulfatase A pseudodeficiency and a third case had most probably Pelizaeus Merzbach disease, two cases had infantile Metachromatic leukodystrophy [6.66%], while another two had congenital muscular dystrophy. All other patients need further follow up and further investigations

effect of diet on antioxidant status in patients with galactosemia

Galactosemia is an autosomal recessively inherited disorder of galactose metabolism. It has good prognosis, if detected in neonatal period or early infancy. Treatment consists of life long dietary restriction of galactose. Present study included eight patients with galactosemia on dietary treatment, five of them had galactose-1-phosphate uridyltransferase deficiency known as classical galactosemia and three had uridine-diphosphate galactose-4' epimerase deficiency. Clinical evaluation of patients under galactose restricted diet and assessment of the antioxidant status in response to dietary therapy was done. Delayed milestones were present in all patients, jaundice at birth was present in 4 and low birth weight was present in 3 patients. Craniofacial dysmorphism was present in 5 patients. Hepatomegaly was present in 6 patients. MRI of the brain showed brain atrophy in 3 patients and demyelination in 2 patients. There was cataract in 7 patients. The levels of zinc, copper, iron, calcium, phosphate, magnesium, selenium, manganese, beta-carotene and vitamin A were evaluated in the blood of galactosemic patients on galactose restricted diet and a comparison between trace elements, beta-carotene and vitamin A in studied patients with galactosemia and controls was done. Copper, calcium, phosphate, manganese and beta-carotene levels in blood were significantly decreased in our patients [p<0.001] than in controls. These findings suggest that patients on galactose restricted diet are at risk of oxidative stress. The data emphasize the importance of dietary supplementation with an antioxidant containing beta-carotene, calcium, copper, selenium and manganese to inhibit oxidative stress in these patients. Consequently this will minimize the neurological deficits improve bone mineralization, reduce the development of retinopathy and damage to liver cells in patients with galactosemia

effect of diet on antioxidant status in patients with galactosemia

Galactosemia is an autosomal recessively inherited disorder of galactose metabolism. It has a good prognosis, if detected in neonatal period or early infancy. Treatment consists of life long dietary restriction of galactose. Our study included eight patients with galactosemia on dietary treatment, five of them had galactose-1-phosphate unidyltransferase deficiency known as classical galactosemia and three had uridine-diphosphate galactose-4' epimerase deficiency. Delayed milestones were present in all patients, jaundice at birth was present in 4 and low birth weight was present in 3 patients. Craniofacial dysmorphism was present in 5 patients. Hepatomegaly was present in 6 patients. MRI of the brain showed brain atrophy in 3 patients and demyelination in 2 patients. There was cataract in 7 patients. The aim of this study was to asses the antioxidant status in response to dietary-therapy. The levels of zinc, copper and Iron, calcium, phosphate, magnesium, selenium, manganese, beta-carotene and vitamin A were evaluated in the blood of galactosemic patients on galactose restricted diet. Also, a comparison between trace elements, beta-carotene and vitamin A in studied patients with galactosemia and controls was done. Copper, calcium, phosphate, manganese and beta-carotene levels in blood were significantly decreased in our patients [p<0.001] than in controls. These findings suggest that treated galactosemic patients are at risk of oxidative stress and abnormal bone mineralization. Therefore, therapeutic intervention in these cases should be more appropriately targeted. The data emphasise the importance of antioxidants and trace elements in minimizing the neurological deficits in galactosaemic patients