A descriptive study of inflammatory bowel disease at an Egyptian tertiary care center.

INTRODUCTION AND AIMS: Inflammatory bowel disease (IBD) is a group of chronic intestinal disorders that trigger prolonged inflammation of the digestive tract. Its incidence and prevalence appear to be increasing in the African population and in Egypt. The present study aims to highlight the pattern and management of IBD in Egyptian patients. MATERIALS AND METHODS: Two hundred patients with IBD were assessed for ulcerative colitis (UC), through the Mayo score, and for Crohn's disease (CD), with the Crohn's disease activity index (CDAI). RESULTS: Median patient age was 35 years, with a predominance of females. UC was more common than CD (88% and 12%, respectively) and severity was moderate, in the majority of cases. Most UC patients had left-sided lesions, whereas ileitis was the most common finding (37.5%) in the CD patients. Proctitis was the least common finding in both diseases and Crohn's fistulizing disease was detected in 4.1% of the patients. Interestingly, peripheral arthropathy was the most common extraintestinal manifestation in the IBD patients (70%) and axial arthropathy was the least common (6%). Severe ocular or mucocutaneous involvement was very rare. Finally, biologic treatment was prescribed to 15.4% of the UC patients and 20.8% of the CD patients. CONCLUSIONS: Although the clinical presentation of IBD in Egypt is comparable to that reported worldwide, diagnoses were found to be delayed. There were fewer cases of CD than UC, but more mild-to-moderate disease severity. The surveillance of patients with IBD must continue and awareness of the disease in the Egyptian medical community needs to increase. A national registry must be established, multicenter studies need to be conducted, and molecular diagnostics is recommended.

Cytogenomic characterization of 1q43q44 deletion associated with 4q32.1q35.2 duplication and phenotype correlation.

BACKGROUND: Microdeletion of 1q43q44 causes a syndrome characterized by intellectual disability (ID), speech delay, seizures, microcephaly (MIC), corpus callosum abnormalities (CCA) and characteristic facial features. Duplication of 4q is presented with minor to severe ID, MIC and facial dysmorphism. We aimed to verify the correlation between genotype/phenotype in a patient with 1q43q44 deletion associated with 4q32.1q35.2 duplication. CASE PRESENTATION: We report on a 3 year-old female patient with delayed motor and mental milestones, MIC and facial dysmorphism. She is a child of non-consanguineous parents and no similarly affected family members. CT brain showed abnormal gyral patterns, hypogenesis of corpus callosum and bilateral deep Sylvian fissure. Electroencephalogram showed frontotemporal epileptogenic focus. Her karyotype was revealed as 46,XX,add(1)(q44). Fluorescence in situ hybridization (FISH) using whole chromosome paint (WCP1) and subtelomere 1q revealed that the add segment was not derived from chromosome 1 and there was the deletion of subtelomere 1q. Multiple ligation probe amplification (MLPA) subtelomere kit revealed the deletion of 1q and duplication of 4q. Array CGH demonstrated the 6.5 Mb deletion of 1q and 31 Mb duplication of chromosome 4q. CONCLUSION: The phenotype of our patient mainly reflects the effects of haploinsufficiency of AKT3, HNRNPU, ZBTB18 genes associated with duplication of GLRA3, GMP6A, HAND2 genes. Patients presented with ID, seizures, MIC together with CCA are candidates for prediction of 1q43q44 microdeletion and cytogenomic analysis.

Oxidative Stress -a Phenotypic Hallmark of Fanconi Anemia and Down Syndrome: The Effect of Antioxidants.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of leukemia-prone diseases such as Fanconi anemia (FA) and Down syndrome (DS). AIM: To explore the oxidative stress state in children with DS and FA by estimating the levels of antioxidants (e.g., malondialdehyde [MDA], total antioxidant capacity, and superoxide dismutase [SOD] activity) and DNA damage, and to evaluate of the effect of antioxidant treatment on these patients. SUBJECTS AND METHODS: The study included 32 children clinically diagnosed with (15 patients) and FA (17 patients) in addition to 17 controls matched for age and sex. MDA, total antioxidant capacity, SOD activity, and DNA damage were measured. Antioxidants including Vitamin A, E, and C were given to the patients according to the recommended daily allowance for 6 months. Clinical follow-up and re-evaluation were conducted for all patients. Laboratory tests including complete blood count, karyotyping, DNA damage, and oxidative stress were re-evaluated. Statistical analysis was performed using statistical computer program Statistical Package for the Social Sciences version 14.0. RESULTS: Children with FA and DS had elevated levels of oxidative stress and more DNA damage than controls. Oxidative stress parameters and DNA damage improved in FA and DS patients after antioxidant administration. CONCLUSION: Early administration of antioxidants to FA and DS patients is recommended for slowing of the disease course with symptoms amelioration and improvement of general health.

Terminal 2q deletion and partial trisomy chromosome 15q: a clinical and cytogenetic study.

We report on a 5 years old female patient with a karyotype 46, XX, add (2), t(2;15) (q37;q22) associated with dysmorphic facial features, digital deformities, heart defect (mild mitral regurge) and severe mental retardation. This is the third reported case worldwide on the terminal 2q deletion and trisomy of chromosome 15q syndrome. The findings in this case and our literature review, delineates the pattern of malformations secondary to trisomy of 15q and deletion of 2q.

Biallelic mutations at PPARG cause a congenital, generalized lipodystrophy similar to the Berardinelli-Seip syndrome.

We present an individual with a generalized and infantile onset lipodystrophy who later developed hypertriglyceridemia, pancreatitis, refractory diabetes, irregular menses and renal failure. She showed the hallmark features of a congenital, generalized lipodystrophy (CGL). Sequencing PPARG identified two pathogenic mutations; c.413_416delAATG; p.Glu138ValfsX168 and c.490C>T; p.R164W. The phenotype and presence of two mutations suggests that biallelic mutations at PPARG cause a CGL similar to that observed with biallelic AGPAT2 or BSCL2 mutations.

Holoprosencephaly spectrum among Egyptian patients: clinical and cytogenetic study.

We report 24 patients with holoprosencephaly (HPE) spectrum screened for Del 7q36 and subtelomere 13q. They were divided according to the type of HPE into: 6 alobar, 15 semilobar, 1 lobar and 2 middle interhemispheric variant (MIH). All patients presented with global developmental delay. Microcephaly was in 83.3% and midfacial developmental defects were in the form of; cyclopia, arrhinia and agnathia in 2 patients (8.3%), premaxillary agenesis in 2 patients (8.3%), cleft lip and palate in 7 patients (29.2%), hypotelorism in 8 patients (33.3%) and hypertelorism in 9 patients (37.5%). The neurological deficits were as follows: abnormal tone and spasticity were present in all of them with exceptional of a single patient with MIH who presented with hypotonia and was able to walk independently at the age of 3 years, athetoid and/or dystonic movements of limbs in 22 patients, seizures in twelve patients (50%) and abnormal EEG in 15 patients (62.5%). Poor temperature regulation was found in 50% of patients and diabetes insipidus was documented in 3 patients (12.5%). The MRI showed complete or partial fusion of basal ganglia and thalami in 21 patients (87.5%) and 19 patients (79.2%) respectively, fused mesencephalon in 8 patients (33.3%), incomplete separation of mesencephalon from diencephalon in 4 patients (16.7%), dorsal cyst in 10 patients (41.7%), abnormal gyral pattern anteriorly in 15 patients (62.5%), anterior located sylvian fissures in 22 patients (99.7%), complete or partial agenesis of the corpus callosum (ACC) in all patients and Dandy-Walker malformation (DWM) in three patients (12.5%). A small occipital cephalocele was detected clinically and radiological as atretic type in MIH patient. Karyotype analysis demonstrated 47, XY+13 in a patient with alobar holoprosencephaly, 46, XY,t(12;13) (q13q24.1;q14q33) in a semilobar case associated with DWM, 46, XY, del(13)(q34) in one semilobar case and three cases had del 7q36 using FISH technique in two semilobar cases and one lobar case. Conclusion: This study highlights the clinical spectrum in patients with HPE and report a case of HPE and DWM associated with t(12;13). Neuroimaging delineated the pathogenesis underlying developmental defects in HPE. Accurate molecular diagnosis is crucial for further understanding of the pathogenesis of HPE.

Clinical and cytogenetic study of a non mosaic 46, X, isodicentric Yq in an Egyptian patient with Turner syndrome.

UNLABELLED: We report on a female with Turner syndrome phenotype and an isodicentric Y chromosome 46, X, idicYq a combination which has to the best of our knowledge not been reported before. OBJECTIVE: To delineate the phenotypic spectrum (clinical and gonadal features) for a female patient with 46, X, + marker karyotype. PATIENTS AND METHODS: The study included a female patient referred to the Clinical Genetics Department, National Research Centre, Egypt. Our patient was subjected to clinical examination and chromosome analysis by GTG banding techniques. Fluorescence in situ hybridization (FISH) was done to identify the marker chromosomes detected by conventional methods. RESULTS: The patient presented with bilateral lymphedema of upper and lower limbs since birth. Craniofacial anomalies (epicanthal folds, broad nasal bridge, long philtrum, protruded tongue, low set ears, short neck), genital ambiguity, with variable Turner stigmata and normal height were detected. Chromosome analysis revealed non mosaic 46, X, + marker. FISH showed 46, X, isodicentric Yq, SRY was negative and deletion ofYp subtelomere. CONCLUSION: To our knowledge, such an association has not been previously described. Further elucidation to pinpoint the level of the defect of major Y genes is of great clinical significance for better phenotype/karyotype correlations.

Ring chromosome 15: expanding the phenotype.

Ring chromosome 15 is a rare disorder, with less than 50 cases reported in the literature to date. We report the clinical and cytogenetic evaluation of a patient with ring chromosome 15. Diagnostic tests including echocardiography, abdominal ultrasound, brain computerized tomography (CT), magnetic resonance imaging (MRI) and electroencephalogram (EEG) were done. Clinical examination of the patient revealed the characteristic features of ring chromosome 15, such as growth retardation, hypertelorism, frontal bossing, a highly arched palate, small hands and feet and café-au-lait spots. In addition, the patient presented with a mild intellectual disability, a congenital atrial septal heart defect, and abnormal EEG records. We also report 2 novel findings, which to our knowledge; have not been reported before in ring chromosome 15 patients: large areas of hyperpigmentation on the front of both legs and feet and hypogenesis of the corpus callosum. Cytogenetic studies using both conventional G-banding and fluorescence in situ hybridization (FISH) with a Sub Tel 15q probe confirmed the diagnosis of ring chromosome 15.

Clinical and cytogenetic study of a case with familial chromosomal translocation presenting with facial dysmorphism and axial neuropathy.

We report on a 9-year-old female patient presenting with muscle weakness, facial dysmorphism and mild mental retardation. She had low birth weight, developmental delay, hypotonia and hyporeflexia and difficulties in climbing the stairs. EMG revealed axonal polyneuropathy affecting both upper and lower limbs. She was the child of non-consanguineous parents, her cytogenetic findings revealed 46,XX,t(12;14)(q14;q23). The mother's karyotype was normal 46,XX while the father's karyotype was 46,XY,t(12;14)(q14;q23) the same as his daughter. Her normal sister's karyotype was also 46,XX,t(12; 14) (q14;q23). Fluorescence in situ hybridization (FISH) was used to elucidate the breakpoints and Array-CGH was done for the patient to confirm the balanced translocation. This observation is of interest because it represents a rare case of a balanced translocation with abnormal phenotype. Mutant genes causing axonal neuropathy have been located on various chromosomes other than 12q14 or 14q24. This report shows the importance of molecular cytogenetics and its correlation with abnormal phenotype and the possibility of another gene locus at the presently studied chromosomal breakpoints. Detailed correlations between chromosome aberrations and their phenotypes are of invaluable help in localising genes for axonal polyneuropathy.

The most encountered groups of genetic disorders in Giza Governorate, Egypt.

This study presents the prevalence, relative frequency, and analysis of genetic diseases/malformations in 73260 individuals. Cases included were ascertained from: Pediatric outpatient clinics of two governmental hospitals and two primary health care centers (PHCCs) in Giza Governorate; Neonatal intensive care unit (NICU) in the selected hospitals and Outpatients Human Genetics Clinics (NRC). 62819 persons visited the outpatients clinics of selected hospitals and PHCCs in Giza governorate. Out of these persons 731 cases (1.16%) proved to have known genetic disorders or malformations. 7755 neonates were delivered in the selected hospitals. Out of these neonates 666 newborns entered NICU and 3% (20 neonates) of them had genetic or congenital disorders. Also, 2686 patients were ascertained from the Human Genetics Clinics, NRC. The overall parental consanguinity rate among the 3417 diagnosed cases was 55%, ranging from 29.5-75%. The study showed a high prevalence of genetic/malformation disorders among Egyptians, with frequencies comparable to other Arab populations (Tab. 4, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

Mandibuloacral dysplasia: a report of two Egyptian cases.

Mandibuloacral dysplasia (MAD) is a rare disorder. Only 35 patients, coming from 22 families, have been reported worldwide. We report on two Egyptian unrelated girls with MAD. The first patient presented at the age of 5 years with acral defect and partial alopecia. The second patient presented at the age of 17 years with progressive micrognathia and loss of subcutaneous fat from the limbs. Physical examination detected the craniofacial, skeletal and cutaneous changes characteristic of MAD. Both patients were short with progeroid facies and loss of subcutaneous fat from the extremities, which fits lipodystrophy type A pattern. Radiological examination revealed delayed closure of cranial sutures, hypoplastic mandible, hypoplastic clavicles, and acroosteolysis. Both patients had normal glucose tolerance, but had fasting and post-prandial hyperinsulinemia, suggestive of insulin resistance. One patient had elevated serum triglycerides and low normal cholesterol levels, while the other patient had normal levels. Serum leptin was normal in both patients. We review the literature on mandibuloacral dysplasia and discuss the differential diagnosis.

Mucopolysaccharidosis type I: clinical and biochemical study.

Of 1240 outpatients referred to the Human Genetics Clinic between 1997 and 1998, 248 (20%) had inborn errors of metabolism, 36 (14%) of which were diagnosed as mucopolysaccharidoses. Parental consanguinity was present in 82% of these patients. Deficiency of alpha-L-iduronidase (IDUA) enzyme in leukocytes and increased urinary mucopolysaccharides excretion were detected in 17 patients. The urinary spot test for glucosaminoglycans was inconclusive in 4 of the 17 cases. Results showed a correlation between the biochemical enzyme activity in leukocytes, the amount of excreted mucopolysaccharides and the subtype and course of mucopolysaccharidosis type I. We conclude that estimation of IDUA enzyme activity in leukocytes can differentiate between clinically overlapping cases of MPS I and MPS II and given the clinical manifestations of MPS I is a definitive and unequivocal method of diagnosis while the urinary spot test is inconclusive.

Mucopolysaccharidosis type I: clinical and biochemical study

Of 1240 outpatients referred to the Human Genetics Clinic between 1997 and 1998, 248 [20%] had inborn errors of metabolism, 36 [14%] of which were diagnosed as mucopolysaccharidoses. Parental consanguinity was present in 82% of these patients. Deficiency of alpha-L-iduronidase [IDUA] enzyme in leukocytes and increased urinary mucopolysaccharides excretion were detected in 17 patients. The urinary spot test for glucosaminoglycans was inconclusive in 4 of the 17 cases. Results showed a correlation between the biochemical enzyme activity in leukocytes, the amount of excreted mucopolysaccharides and the subtype and course of mucopolysaccharidosis type I. We conclude that estimation of IDUA enzyme activity in leukocytes can differentiate between clinically overlapping cases of MPS I and MPS II and given the clinical manifestations of MPS I is a definitive and unequivocal method of diagnosis while the urinary spot test is inconclusive

Hepatocyte nuclear factor 4 inhibits the activity of site A from the rat apolipoprotein AI gene.

The pivotal role of apolipoprotein AI (Apo AI) in mediating reverse cholesterol transport has lead us to the study of transcription factors that influence the expression of this gene. Previous studies show that rat HNF-4 enhances the activity of a cis-acting site C in the rat Apo AI promoter. Since sites C and A share 80% homology, we have examined whether HNF-4 binds to and modulates the transcriptional activity of the A-motif. Results show that HNF-4 binds to site A. The transcriptional activity of site A in a human hepatoma cell line, HuH-7, increases 2-2.5-fold in the presence of antisense HNF-4, but the sense construct has no effect on the activity of the reporter template. The lack of an effect of HNF-4 on site A activity may be due to high endogenous levels of the factor in HuH-7 cells. However, in BHK cells HNF-4 clearly inhibits the transcriptional activity of site A. Together these findings suggest that in contrast to the enhancing effects of HNF-4 on site C, the same factor inhibits site A activity. Since hepatocytes normally contain the T3 receptor and this nuclear factor increases site A action, cotransfection of T3 receptor along with antisense HNF-4 further augments the activity of p5'A.CAT. In summary, rat HNF-4 binds to site A from rat Apo AI DNA, and this factor suppresses site A activity. HNF-4 interferes with the enhancer role of the T3 receptor and thus contributes negatively to the net expression of the Apo AI gene.

Kerosene poisoning in children: a clinico-radiological study of 205 cases.

Clinical, radiological and epidemiological data from 205 children with kerosene poisoning, admitted over a period of four years to the Paediatric Department of the Chest Hospital, are analysed. All children had chest radiographs. Of the 205 children, 94% developed fever, 86% pulmonary complications and 7% neurological sequelae. Vomiting was reported in 65%, abdominal pain in 2% and diarrhoea in 2%. There was no mortality. Analysis of radiological data showed a wide spectrum of pulmonary changes with a high incidence of pleural effusions and pneumatocoeles. The most common abnormal respiratory physical sign was rhonchi, which was detected in 75% of patients with pulmonary involvement. This finding strongly supports the concept that the main pulmonary change caused by kerosene toxicity is small air way obstruction. All patients with central nervous system complications had severe pulmonary involvement, suggesting a close relationship between the severity of pulmonary involvement and the development of neurological complications. These data support the concept that central nervous system complications are mainly due to hypoxia secondary to pulmonary involvement rather than a direct toxic effect of kerosene on the central nervous system.