Newborn screening for certain treatable inborn errors of metabolism in Alexandria

As outlined in the Newborn Screening Task Force report published in August 2000, the newborn screening system is more than the just testing, but also involves follow up, diagnosis, treatment, and evaluation. Newborn screening is aimed at early detection and intervention of treatable inborn errors of metabolism and also at establishing the incidence of these disorders. Specimens of dried blood spots were collected from infants born in Alexandria, attending 13 Health Offices in different Districts of Alexandria for BCG vaccination, and the tests were done in the Human Genetics Department, Medical Research Institute, Alexandria University. The total number screened was 3000 infants, of them; one [0.033%] infant had hyperphenylalaninemia, one [0.033%] infant had classic galactosemia and 11 [0.37%] infants had high level of thyroid stimulating hormone [TSH], on confirmatory test, 9 of them were found to be euthyroid

Maternal serum alpha fetoprotein among pregnant females in Alexandria

Maternal serum alpha fetoprotein [MSAFP] was introduced as a screening test for congenital malformations especially neural tube defects [NTDs] two decades ago. However, many factors were known to affect its level. From these are racial differences and maternal weight. The aim of the present work is to illustrate the normal distribution of MSAFP among working pregnant women in Alexandria in gestational age 16- 18 weeks, to identify some of its determinants, and to determine the specificity and sensitivity of MSAFP for the detection of congenital anomalies and adverse pregnancy outcome. A sample of 608 pregnant working women who were 16-18 week gestation was recruited for the study from the antenatal clinic affiliated to Gamal Abdel Nasser Health Insurance Hospital in Alexandria. The enrolled women were interviewed using a structured questionnaire and a blood sample was collected from each of them to measure the level of MSAFP. At the expected time of delivery, Gamal Abd el Nasser Health Insurance Hospital was visited to collect data about the outcome of pregnancy of the enrolled women. The median of MSAFP level for deliveries with no congenital anomalies were 25.5, 33.5, and 53.2 IU/ml, at gestational weeks 16, 17 and 18 respectively. The significant variables related positively to MSAFP level included abortion or stillbirth, congenital anomalies in the index pregnancy, gestational age, bleeding during pregnancy, gestational diabetes, twin pregnancy, consanguinity between maternal parents, history of congenital or genetic diseases in maternal family, and caesarian section deliveries. Fatigue score was negatively correlated to MSAFP level. Using MSAFP multiples of median [MOM], 42.9% of abortions and stillbirths, 57.1% of twin pregnancies, 31. 25% of preterm deliveries and 27.3% of low birth weight had levels of 3 MOM or more. One fourth of the congenital anomalies were below 0.5 MOM and 41.7% were at or above 3 MOM. The sensitivity of MSAFP test for the detection of NTDs [cutoff point 2.5+ MOM] or Down syndrome [cutoff point <0.5 MOM] among the study sample was 100% [Cl: 19.8-100%]. Specificity for NTDs was 92.7% [Cl: 90.3-94.6%], while the specificity for Down syndrome was 89.1% [86.3-91.4%]. The sensitivity for adverse pregnancy outcome [cutoff point <0.5 or 2.5+ MOM] was 41.6, and the specificity was 85.8%.In conclusion, the cutoff points of MSAFP of the study sample are different from those for other populations. Different factors affect the level of MSAFP including adverse pregnancy outcomes. It is recommended to introduce antenatal screening for congenital anomalies as a routine screening test during pregnancy using levels adapted from the local population for cutoff point determination

Genetic study of syndromic inherited deafness

The study comprised 25 patients with Syndromic genetic hearing loss. They were selected from the Audiology Unit, Faculty of Medicine, and the Human Genetics clinic, Medical Research Institute, Alexandria University. Their ages ranged from 2.5 to 19 years. Males were more affected than females [M/F ratio = 2:1]. The high parental consanguinity [63.2%] emphasizes the contribution of autosomal recessive gene or multiple genes in the etiology of deafness. Thorough clinical examination, and complete investigation including metabolic screening tests, cytogenetic studies and other specific investigations, together with pedigree analysis were the main criteria for diagnosis. Fundus examination was essential as ocular involvement was found in association with most cases of genetic hearing loss. Results of the studied patients revealed that deafness was inherited either dominantly, recessively or in X-linked manner in association with other anomalies in the following syndromes: Down syndrome [one case, 4%], external ear malformation [4%], distal arthrogryposis [one case, 4%], Optic atrophy and ataxia [one case, 4%], Stickler-Wagner syndrome [one case, 4%], Usher syndrome [2 cases, 8%], Waardenburg syndrome types I and II [2 cases, 8%], Charcot-Marie-Tooth syndrome [2 cases, 8%], Alport syndrome [3 cases, 12%], Pendred syndrome [5 cases, 20%], and Hunter syndrome [3 cases, 12%]. For the idiopathic cases [2 cases, 8%], a possible genetic cause was also suggested, probably autosomal recessive

Chromosome damage in passive smoker female

Current epidemiological data associates passive smoking with health hazards which not only affects the passive smoker but also affects the offsprings of passive smoker females. To determine the effect of cigarette smoke on the chromosomes of passive smoker females who were still in the childbearing age, the micronucleus [MN] frequency in 20 passive smoker females [spouse smoker] who had been exposed to cigarette smoke for at least 5 years was compared to the MN frequency in 20 control subjects [females with non-smoking spouse] all in the age group 31-39 years. The MN frequency among passive smoker female group ranged from 16-27 MN/500 cytokinesis blocked [CB] binucleated cell, with a mean of 21.1 +/- 3.7, while the MN frequency among the control group ranged from 3-11 MN/500 CB binucleated cell, with a mean of 8 +/- 1.7. The difference is statistically significant [t=14.2, p<0.01]. Applying the correlation coefficient test between age and MN frequency, a weak positive though non significant correlation was found between age and MN frequency in the passive smoker female group [R=0.11, p=0.630] while an intermediate positive but still non significant correlation was found between age and MN frequency in the control [R=0.26, p=0.27]. There was a positive correlation between the duration of exposure to cigarette smoke and the MN frequency, but this was statistically non significant [R=0.33, p=0.125]. The results emphasize that mothers especially in the childbearing age should not be exposed to cigarette smoke to avoid its deleterious effects on their health thus preventing any harmful effect the smoke can have on their offsprings

Role of parental age and consanguinity in the etiology of numerical chromosome anomalies

To investigate the role of parental age and consanguinity on nondisjunction, 257 patients with numerical chromosome anomalies [NCA] were studied. For comparison, 514 phenotypically normal newborns were selected. The mean maternal age was significantly higher in the group with NCA than in the control group. The mean paternal age was significantly higher in the group with NCA than in the control group. The frequency of consanguineous marriages among parents of patients with NCA was also significantly higher than among parents of the control group. Thus, advanced maternal age and consanguinity were found to play an important role in the etiology of nondisjunction while the effect of advanced paternal age is probably of a minor value

Genetic, clinical, radiological study of monogenic phakomatoses

The study comprised 29 patients with features suggestive of phakomatoses refered to the Human Genetic Clinic, Medical Research Institute, and Dermatology Department, Faculty of Medicine, Alexandria University. All the patients were subjected to complete genetic history, pedigree analysis, clinical genetic, dermatological examinations, radiological investigations [X-ray, Ultrasonography and CT] and cytogenetic study in some patients. The result revealed that: 19 patients had neurofibromatosis [NF], 17 had NF I, one patient had Cafe au-lait type and the last one had segmental type. NF is the most common type of phakomatoses and is inherited as autosomal dominant. Eight patients had chromosomal instability syndromes [4 had xeroderma pigmentoza, 2 had De Sanctis Cacchione syndrome and 2 had ataxia telangiectasia]. Increased chromosomal breaks among these patients were detected by special technique. Chromosomal instability syndromes are inherited as autosomal recessive. The last 2 female patients were diagnosed as focal dermal hypoplasia syndrome [FDH] which is an X-linked dominant phakomatoses. In phakomatoses regular follow up examination and genetic counseling with emphasis on new symptoms are necessary to allow early intervention, detection of

Cytogenetic study in idiopathic infertile males

Sex chromatin investigations, including X- chromatin and Y-chromatin, was carried out on one hundred idiopathic infertile males with marked oligospermia or azoospermia. Seven cases [7%] were X-chromatin positive, 18% of the cases had aberrant Y-body [10% big Y, 7% small Y and 1% double Y]. Such Y-chromosome abnormalities were frequent among azoospermic than oligospermic males. Chromosomal analysis of patients with positive X-chromatin and/or abnormalities of the chromosome showed chromosomal abnormalities in the seven azoospermic cases [7%] which were X-chromatin positive. These chromosomal abnormalities varieties of mosaic Klinefelter. Six patients [6%] were 46,XY/47,XXY mosaic and one patient [1%] was 46,XY/47,XXY/48,XXYY mosaic. In conclusion, chromosome analysis as well as sex-chromatin analysis is necessary in the investigation of male infertility