Search

Background: Duchenne muscular dystrophy is associated with variable physical and psychosocial sequalae, to patients and their caregivers. Aim: This study aimed to assess quality of life in various dimensions in children with Duchenne Muscular Dystrophy (DMD) and in their caregivers. Patients and methods: This study included all children diagnosed with Duchene Muscular Dystrophy (DMD) registered in the Pediatric Neurology Clinic of Alexandria University Specialized Children’s Hospital. Pediatric Quality of Life (PedsQL ™ 3.0) Duchenne Muscular Dystrophy Module was applied to the children and their caregivers. Results: In toddler group, the mean score was 34.41 ± 26.84 SD for daily activity, 48.64 ± 21.41 SD for medications, 28.71 ± 20.70 SD for anxiety, 60.15 ± 21.01 SD for communication and 42.98 ± 15.41 SD and for total quality of life. In parents’ group, the mean scores were as following: 45.35 ± 30.66 SD for daily activity, 50.32 ± 18.79 SD for medications, 20.40 ± 19.32 SD for anxiety, 54.59 ± 20.92 SD communication and 42.55 ± 14.86 SD for total quality of life. Conclusion: Duchenne muscular dystrophy causes significant impairment in all aspects of quality of life in patients and their caregivers.

Gaucher disease (GD) is the most common lysosomal storage disorder, the aim of the current study was to investigate hyperimmunoglobulinemia and abnormalities of serum immunoglobulin G (IgG) subclasses in children with GD and the relation of those findings to the GD phenotype and genotype, duration of enzyme replacement therapy (ERT), and infection frequency. The study included 20 Egyptian children with GD receiving ERT and 20 age-matched and sex-matched healthy children as controls. Serum Ig and serum IgG subclass levels were measured in the children with GD. Serum IgG subclass levels were measured in the control subjects. Hyperimmunoglobulinemia was present in 15 of the 20 (75%) children with GD. In addition, it is found significantly lower IgG2 levels and significantly higher IgG3 levels in the GD group than in the control group (P

Background Down syndrome (DS) is the most common genetic disorder with more probability of recurrent infections. Aim This study aimed to determine the differences in lymphocyte subgroups (CD4 and CD8) between DS children and to study the pattern and likelihood for recurrent infections and hospital admission due to infection. Patients and methods This study was carried out in the Genetic Unit of Alexandria University Children’s Hospital, Egypt. The study enrolled 61 individuals with DS. They were assessed for recurrent infections [including otitis media, pneumonia, upper respiratory tract infections (URTIs), and gastroenteritis] and hospital admission due to infections. All patients were subjected to complete blood count and flow cytometric analysis for expression markers of T lymphocytes (CD4 and CD8). Results The authors found a statistically significant increase in the frequency of URTIs. In terms of the type of recurrent infection in DS, it was the highest for URTIs. A statistically significant decrease was found in CD4 in the DS patients. Nonsignificant correlations were found between CD markers and hospital admission. Conclusion An increase in the incidence and the recurrence of infections among children with DS, especially URTI, pneumonia and gastroenteritis, was reported in the present work. Children with DS showed decreased absolute CD4 and CD4/CD8 ratio less than normal values of similar children younger than 6 years of age. Also, normal or even increased levels of absolute CD8 were evident in children with DS.

Background Celiac disease (CD) is an immune-mediated disease affecting the small intestine secondary to gluten exposure. The currently available treatment is lifelong adherence to a gluten-free diet. Several disorders have a higher risk to develop CD, including Down syndrome (DS). In several studies, the prevalence of CD in DS ranged between 4 and 17%. CD is prevalent in Arabs; however, few studies have been performed to determine the prevalence of CD in DS patients. Aim This study aimed to estimate the prevalence of CD in Egyptian children with DS. Patients and methods This study was performed as a cross-sectional study. The patients were recruited from the Genetics Outpatient Clinic at Alexandria University Children Hospital. Screening for CD was done by using only serological markers: anti-tissue transglutaminase-immunoglobulin A (IgA) and total IgA followed by anti-endomysial antibody and small bowel biopsy for positive cases. HLA typing was not performed before serology. Results The total number of the study sample was 54. The mean age was 4.26±1. 94 years ranging from 2 to 12 years; 61.1% of cases were men. All studied children had normal serum total IgA. Serum transglutaminase-IgA was elevated in three (5.6%) cases. Endomysial antibody was positive in two of them. Histopathological analysis confirmed the diagnosis of CD in two (3.8%) patients; one of them was completely asymptomatic. Conclusion Our study showed a confirmed prevalence of 3.8% for CD in the studied Egyptian patients with DS based on serology and biopsy. This result indicates the need for regular screening of these patients for CD.

Gaucher disease (GD) is an autosomal recessive lipid storage disorder, caused by deficient activity of the lysosomal enzyme b-glucocerebrosidase, resulting in accumulation of glucocerebroside in tissue macrophages. HGT-GCB-068 was an open-label study designed to explore the efficacy and safety of velaglucerase alfa in children and adolescents with type 3 GD, a neuronopathic form of the disease. Six treatment-naive patients received infusions of velaglucerase alfa every other week at 60 U/kg over 12 months. Velaglucerase alfa demonstrated a favorable tolerability profile, and 1 infusion-related reaction (headache) was the only drug-related adverse event reported. Numerical increases from baseline in hematological parameters and decreases in visceral parameters were seen at 12 months. http://ClinicalTrials.gov identifier NCT01685216.

Background The eye is second only to the brain as an individual organ in its frequency of involvement in genetic disorders. The array of ocular findings associated with developmental disorders, metabolic diseases, and chromosomal anomalies is endless. Aim To determine the prevalence and describe types of ocular malformations among patients with genetic disorders attending the Genetic Clinic of Alexandria University Children’s Hospital from January 2015 to December 2017. Patients and methods In this study, 354 patients were included. Patients’ data were collected from records as follows: the age and sex of the patients, residence, parental consanguinity, family history, pre/perinatal history, and data of general examination and ophthalmic examination. Results Of 354 patients who were enrolled in this study, 83 (23.4%) patients had genetic ocular malformations, 16 cases had corneal clouding, 15 cases of ptosis, 10 cases of strabismus, nine cases of refractive errors, and six cases of microphthalmia. The age variation in the study was between 8 days and 14 years, and 55.4% of cases were below the age of 2 years. Male : female ratio was 1.1 : 1. Overall, 61.4% of cases had positive history of consanguineous marriage, and 9% of cases had a positive prenatal history. Moreover, 4.8% of cases with ocular malformations had chromosomal abnormality, in which 3.6% were numerical (Trisomy 13) and 1.2% were structural (deletion 18q). Genetic diseases associated with ocular malformations could be classified into isolated (nonsyndromic) disorders, which represented 3.6%, and syndromic disorders, which represented the remaining 96.4% of cases. Isolated disorders included primary microcephaly (2.4%) and blepharophimosis, ptosis, and epicanthus disease (1.2%), whereas the syndromic cases included chromosomal disorders (4.8%), metabolic disorders (26.5%), syndromes with primary dermatological abnormalities (7.2%), syndromes with primary skeletal abnormalities (19.2%), syndromes with endocrine/growth retardation (28.6%), syndromes with primary neurologic abnormalities (7.2%), and others (4.2%). Conclusion Overall, 23.4% of patients with genetic syndromes had ocular malformations. The most common anomaly was congenital corneal clouding (19.3%) followed by ptosis (18%), strabismus (12%), refractive errors (10.8%), and microphthalmia (7.2%) in the order of frequency.

Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, not linked to the 10p11.23 locus, whose two affected children have a homozygous mutation in SMOC1. Knockdown experiments of the zebrafish smoc1 revealed that smoc1 is important in eye development and that it is expressed in many organs, including brain and somites.

The aim of the study is to characterize markers of apoptosis in children with acute lymphoblastic leukemia (ALL) in relation to treatment outcome of the disease. The study was performed on 34 children with ALL and 39 healthy children as a control group. Apoptosis was assessed by cell morphology; DNA fragmentation; ELISA and RT-PCR for CD95, CD95L, BcL-2 and nuclear factor-kappa B (NF-kappaB); and flow cytometry for CD95, CD40, CD49d and CD11a. Apoptosis was significantly lower in patients than controls. Apoptosis detected by CD95 ligand was significantly lower in cases with no remission after treatment than those who achieved remission. Anti-apoptotic factors: CD40, BcL-2, and NF-kappaB were all found to be higher in cases than controls and in cases with no remission than those achieved remission. CD49d was significantly lower in cases than controls, and significantly lower in cases with who did not achieve remission. CD11a levels were similar in the various groups. Delayed apoptosis of ALL cells is genetically controlled either directly or indirectly by a network of oncogenes and tumor suppressor genes. CD40 appeared to stimulate both T and B lineage and is considered the most potent influencer and predictor of resistance to therapy. Inhibitors for the activity of CD40, Bcl-2 and NF-kappaB as well as stimulants to CD95 could have a potential therapeutic benefit.

Purpose: To report the clinical and genetic study of a child with bilateral anophthalmia. Methods: A 14-year-old Egyptian boy, born from consanguineous parents, underwent a general and a full ophthalmological examination. Mutation screen of the A/M genes with recessive inheritance was done stepwise and DNA was analyzed by Sanger sequencing. Results: Bilateral anophthalmia, arachnodactyly of the feet and high arched palate were observed on general examination. The parents were first cousins and healthy. Sequencing analysis revealed a novel compound heterozygous mutation in one of the copy of exon 2 of VSX2 and a possible deletion of at least exon 2 on the other allele. Conclusions: A compound heterozygous VSX2 mutation associated with anophthalmia was identified in a patient from an Egyptian consanguineous family. This report brings the number of VSX2 mutation in anophthalmia/ microphthalmia (A/M) to 13. Functional consequences of the reported changes still need to be characterized, as well as the percentage of A/M caused by mutations in the VSX2 gene. This family also shows that despite consanguinity, heterozygous mutations can also happen and one should not restrict the molecular analysis to homozygous mutations.

Gaucher disease is the most prevalent inherited lysosomal storage disorder caused by deficiency of beta-glucocerebrosidase enzyme. Clinically, 3 forms of Gaucher disease are recognized, of which type 1 is the mild to moderately severe, slowly progressive, nonneuropathic form. Bleeding disorders in Gaucher disease are believed to be due to thrombocytopenia but there may be additional factors that influence coagulation and fibrinolysis in Gaucher disease patients. The aim of the present work was to study some coagulation parameters in the Egyptian children with type 1 Gaucher disease. Five newly diagnosed patients and another 5 patients on enzyme replacement therapy (ERT) were enrolled in the study. Their coagulation profile, including coagulation factors, was evaluated. The results showed that in newly diagnosed cases factors II and VII were deficient in 40%, factor V was deficient in 20%, and all the cases had low levels of serum fibrinogen. In patients on ERT, factors VII and VIII were deficient in 60%, factor XI was deficient in 40% and factors V, X, and XII were deficient in 20% of cases. In conclusion, Egyptian patients with type 1 Gaucher disease, whether newly diagnosed or receiving enzyme replacement therapy, experience coagulation factor abnormalities regardless the clinical expression of bleeding diathesis. This should be taken into consideration before these patients are subjected to surgery for, e.g., splenectomy, which is common in these patients.

Anophthalmia or microphthalmia (A/M), characterized by absent or small eye, can be unilateral or bilateral and represent developmental anomalies due to the mutations in several genes. Recently, mutations in aldehyde dehydrogenase family 1, member A3 (ALDH1A3) also known as retinaldehyde dehydrogenase 3, have been reported to cause A/M. Here, we screened a cohort of 75 patients with A/M and showed that mutations in ALDH1A3 occurred in six families. Based on this series, we estimate that mutations in ALDH1A3 represent a major cause of A/M in consanguineous families, and may be responsible for approximately 10% of the cases. Screening of this gene should be performed in a first line of investigation, together with SOX2. (C) 2014 Wiley Periodicals, Inc.

Thalassaemia is a group of inherited haemoglobin disorders characterized by reduced synthesis of one or more of the globin chains leading to imbalanced a /non-a globin synthesis which is the major factor in determining the severity of the disease in the thalassaemia syndromes. In Egypt, beta-thalassemia is the commonest cause of chronic haemolytic anaemia and it represents a major genetic disease and a public health problem. This study included 50 transfusion dependent beta-thalassaemic cases. They were subjected to detailed history taking, physical examination to assess the size of liver and spleen and laboratory investigations including complete haemogram, bone marrow (BM) aspiration, haemoglobin electrophoresis and serum ferritin. Genetic analysis for detection of point mutations was done by PCR amplification refractory mutation system (ARMS) which is a PCR method based on allele specific priming. Using this technology, it was possible to characterize mutations in 73% of beta-thalassaemia cases, while 27% remained uncharacterized. The five common mutations used were: IVS-1-110 (G--A), IVS-1-6 (T--C) IVS-I-1 (G--T), IVS-II-1 (G--A) and codon 39 (C--T). The commonest was IVS-I-110 (62%) followed by IVS-1-6 (7%), then IVS-I-1 (4%). On the other hand mutations such as IVS-II-1 and Cd- 39 were not found in any of our patients. No significant difference was found between different genotypes regarding the frequency of blood transfusion needed, degree of anaemia and microcytosis, HbF% or serum ferritin levels. This may be due to the small sample size of some of the genotypes (IVS-I-110/IVS-I-1IVS-I-110/IVS-I-6) or due to repeated blood transfusions which mask the patient original CBC and Hb electrophoresis pattern or due to co-inheritance of other genetic modifying factors that alter the typical phenotype.