Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. RESULTS: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. CONCLUSIONS: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

Hypoparathyroidism, deafness and renal dysplasia syndrome caused by a GATA3 splice site mutation leading to the activation of a cryptic splice site.

The HDR syndrome is a rare autosomal dominant disorder characterised by Hypoparathyroidism, Deafness, and Renal dysplasia, and is caused by inactivating heterozygous germline mutations in the GATA3 gene. We report an 11-year-old girl with HDR syndrome caused by a heterozygous mutation located at the splice acceptor site of exon 5 of the GATA3 gene (NM_001002295.2: c.925-1G>T). Functional studies using a minigene assay showed that this splice site mutation abolished the normal splicing of the GATA3 pre-mRNA and led to the use of a cryptic splice acceptor site, resulting in the loss of the first seven nucleotides (TCTGCAG) of exon 5 in the GATA3 mRNA. These findings increase the understanding of the mechanisms by which GATA3 splicing mutations can cause HDR syndrome.

Does faecal calprotectin differentiate between inflammatory bowel disease colitis and non-inflammatory bowel disease colitides?

INTRODUCTION: Chronic colitis is a major problem worldwide with high morbidity. Causes of chronic colitis are heterogeneous. A cut-off level of faecal calprotectin to predict inflammatory bowel disease (IBD) as a cause of chronic colitis is lacking. AIM: To study the level of faecal calprotectin in different causes of colitis and to measure the cut-off level to differentiate between IBD and non-IBD colitides. MATERIAL AND METHODS: This prospective study was conducted from June 2018 to May 2019. The study included all patients aged 2 months up to 18 years who were confirmed to have chronic colitis endoscopically and histopathologically attending the Gastroenterology Clinic at Alexandria University Children's Hospital. Faecal calprotectin level was measured. RESULTS: We included 110 patients. Allergic colitis was the commonest cause followed by IBD followed by infectious colitis (50.9%, 38.1% and 6.3% respectively). Faecal calprotectin above 744 µg/g could predict IBD as a cause of chronic colitis with 86.8% specificity and 66.7% sensitivity. Significant elevation of faecal calprotectin was detected in IBD patients. Faecal calprotectin was significantly correlated with C-reactive protein level and erythrocyte sedimentation rate. CONCLUSIONS: Faecal calprotectin could predict the cause of colitis and could aid the paediatrician for early referral of patients with chronic colitis.

Lactoferrin versus iron hydroxide polymaltose complex for the treatment of iron deficiency anemia in children with cerebral palsy: a randomized controlled trial.

Iron deficiency anemia (IDA) is common among children with cerebral palsy (CP), and studies on the efficacy of lactoferrin (Lf) in the treatment of IDA are limited. This study aimed to compare the efficacy of Lf with that of iron hydroxide polymaltose complex (IPC) in the treatment of IDA in children with CP. This randomized controlled study, conducted at Alexandria University Children's Hospital, enrolled 70 children aged 1-10 years with CP and IDA; 35 children randomly received IPC, whereas the other 35 received Lf. Four children withdrew from the study; thus, only 66 children were analyzed (32 in the IPC group and 34 in the Lf group). At baseline, the hemoglobin level and other blood parameters were similar between the two intervention groups. After four weeks of treatment, both the IPC and Lf groups showed significant improvements in hemoglobin (Hb), serum ferritin (SF), serum iron, total iron-binding capacity, mean corpuscular volume, and mean corpuscular hemoglobin from baseline. Upon comparing the two treatment groups, adjusted mean Hb and SF changes in the Lf group were significantly higher than that of the IPC group (p =0.001and p= 0.033, respectively), and constipation was less likely to occur in the Lf group than the IPC group (p = 0.049 ).Conclusion: Lactoferrin is effective and superior to IPC as an oral iron replacement therapy in children with CP and IDA, as it has fewer side effects. What is Known: • Lactoferrin (LF) is a natural glycoprotein capable of treating iron deficiency anemia (IDA). • Studies on the efficacy of Lf in the treatment of IDA in children with cerebral palsy (CP) are limited. What is New? • This trial compared the efficacy of Lf and iron hydroxide polymaltose complex (IPC) as treatments of IDA in children with CP. • Lf is effective and even better than IPC as a treatment of IDA in children with CP, as it has fewer side effects.

Increased Expression of IL-17A and IL-17F Is Correlated With RUNX1 and RORγT in Pediatric Patients With Primary Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is characterized by dysregulated cellular immunity. Interleukin 17 (IL-17) and its secreting cells (Th17) are involved in the pathogenesis of ITP. Retinoic acid receptor-related orphan receptor γt (RORγt) is the chief regulator of Th17 development. The interaction among Runt-related transcription factor 1 (RUNX1) and IL-17-related genes in ITP remains questionable. The study aimed to evaluate the expression of RUNX1 and RORγt together with IL-17A and IL-17F genes in childhood ITP to investigate their contribution to disease pathogenesis and clinical presentation. Ninety children were included, 30 primary active ITP patients, 30 ITP patients in remission after treatment, and 30 healthy controls. The expression levels of RUNX1, RORγt, IL-17A, and IL-17F genes were measured. Significant overexpression of RUNX1, RORγt, IL-17A, and IL-17F genes was observed in active ITP patients, which was restored to normal levels in both ITP patients in remission and controls (P<0.001 for the 4 genes). Positive correlations between RUNX1, RORγt, IL-17A, and IL-17F expression levels were observed in active ITP patients (P=0.001 for RUNX1 with RORγt, P<0.001 for RUNX1 with both IL-17A and IL-17F, regarding RORγtP<0.001 with IL-17A and P=0.002 with IL-17F, P=0.001 for IL-17A with IL-17F). In conclusion, RUNX1 is possibly involved in the molecular pathogenesis of ITP upregulating the expression of Th17-secreted cytokines, IL-17A and IL-17F, through RORγt at the transcriptional level. Thus, targeting RUNX1 or RORγt may be new alternative therapeutic strategies.

Effect of enteral erythropoietin on feeding-related complications in preterm newborns: A pilot randomized controlled study.

BACKGROUND AND STUDY AIMS: To evaluate the effects of enteral administration of recombinant human erythropoietin (rhEPO) on feeding-related complications in preterm infants. PATIENTS AND METHODS: This double-blind, randomized controlled pilot study enrolled 120 preterm infants born ≤ 32 weeks' gestation who were admitted to the neonatal intensive care unit in a tertiary hospital; 60 patients randomly received recombinant human erythropoietin while the other 60 received placebo. Newborns who underwent cardiopulmonary resuscitation, infants with genetic syndromes, infants with inborn errors of metabolism, infants with major congenital or acquired gastrointestinal tract malformations, infants with previous use of parenteral growth factors such as recombinant human erythropoietin and granulocyte-macrophage colony-stimuating factor (GM-CSF) and infants previously treated with intravenous immunoglobulin were excluded. Overall, 48 patients withdrew from the study because of intravenous haematopoietic growth factor intake or death before treatment was completed. A total of 72 preterm infants remained in the study: 36 preterm infants in the erythropoietin (EPO) group, and 36 preterm infants in the placebo group. The day that enteral feeding was successfully started, the time to establishing one-half, two-thirds, and full enteral feedings (reaching at least 150 mL/kg/day), the number of episodes of feeding intolerance, the time to regain birth weight and the incidence of necrotizing enterocolitis (NEC) were recorded. RESULTS: Both groups showed no significant difference in the time to achieve one-half, two-thirds, or full enteral feeding, no signs of feeding intolerance, and no cases of NEC were recorded. CONCLUSION: Enteral erythropoietin does not appear to affect feeding intolerance or NEC incidence.

Hyperimmunoglobulinemia and IgG Subclass Abnormalities in Children With Gaucher Disease.

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<0.001 and <0.006, respectively). Patients with 12 infections per year had significantly higher IgG3 levels compared with patients with 6 infections per year (P=0.022). In conclusion, hyperimmunoglobulinemia and IgG subclass abnormalities occur in children with GD who are on ERT and may be related to recurrent infections.

High prevalence of obesity among infants presenting with intussusception: Findings in an Egyptian cohort.

BACKGROUND AND STUDY AIMS: Intussusception is a life-threatening illness, with incompletely understood aetiology, although some predisposing factors are known. Intussusception frequently occurs in well-nourished chubby infants. We aimed to determine whether patients presenting with intussusception have a high prevalence of obesity. PATIENTS AND METHODS: This cross sectional study was conducted in 100 infants presenting with intussusception aged ≤2 years at the Paediatric Surgery Department. Anthropometric measures, history of recent upper respiratory tract infection, timing and type of intervention were recorded. A near median split divided the population into younger (aged < 8 months, N = 47) and older (8-24 months, N = 53) groups. Obesity was defined as having a body weight for length ≥ 97.7th centile on WHO growth charts. RESULTS: The study comprised 58 boys and 42 girls, 31% of whom had upper respiratory infection in the preceding month. Obesity was present in 18% of patients, based on WHO growth charts. There was a trend towards higher percentage of obese infants within the younger (25%) compared to older age groups (12%, P = 0.085), but no gender difference. Obesity did not influence the rate of success of hydrostatic reduction. Based on Egypt-specific growth charts, the percentage of infants with a weight-for-age centile ≥ 85th was 42%, of whom 7% were ≥ 97.7th centile. The corresponding percentages for the weight-for-length were 29% and 15% of patients respectively. CONCLUSION: There is a high prevalence of obesity in infants presenting with intussusception, particularly under 8 months of age. The mechanistic link between obesity and the pathogenesis of intussusception deserves investigation.

Bone Mineral Density and Vitamin D Receptor Genetic Variants in Egyptian Children with Beta Thalassemia Major on Vitamin D Supplementation.

BACKGROUND: Low bone mineral density (BMD) is a characteristic feature of Beta thalassemia major (ßTM) patients. Vitamin D is important for bone mineralization. Vitamin D receptors (VDR) genetic variants may be related to vitamin D status and BMD. OBJECTIVES: To evaluate the effect of VDR genetic variants on vitamin D levels and BMD in ßTM Egyptian patients supplemented with vitamin D. METHODS: This study was conducted on forty children with ßTM and seventeen unrelated healthy sex and age-matched controls. Serum calcium, phosphorus, alkaline phosphatase, ferritin, and vitamin D were measured. VDR genetic variants (BsmI, TaqI, and FokI) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD was measured by dual-energy X-ray densitometry (DEXA) of the lumbar spine. RESULTS: In ßTM patients, 22.5% had insufficient, and 77.5% had sufficient levels of vitamin D, and no cases had vitamin D deficient. BMD Z score was significantly lower in ßTM patients compared to controls (p<0.001). Osteopenia and osteoporosis of lumbar spines were observed in 70% and 22.5% of ßTM patients respectively. BsmI bb and FokI Ff and ff genotypic variants were significantly associated with lower vitamin D and BMD Z score. No association was observed with TaqI genotypic variants. CONCLUSIONS: Low BMD is prevalent in patients with ßTM despite vitamin D supplementation. The BsmI bb, FokI Ff and ff genotypic variants of VDR can be considered as risk factors for the occurrence of osteoporosis in these children.

Intraosseous Versus Intravenous Access in Pediatric Septic Shock Patients Admitted to Alexandria University Pediatric Intensive Care Unit.

The cornerstone of emergency management of sepsis is early, goal-directed therapy. The purpose of this study was to evaluate the effect of intraosseous (IO) vs. intravenous (IV) access for resuscitation of patients with septic shock admitted to pediatric intensive care unit. This prospective interventional randomized clinical trial study was conducted on 60 patients with septic shock who need rapid administration of fluids and drugs; 30 cases were randomly chosen for IO vascular access, while the other 30 were selected for IV access. The IO route was successfully secured in all cases with a significant shorter time of vascular access insertion, shorter length of stay and reduction in mortality in IO group vs. IV group (p = 0.001, 0.045, 0.002, respectively). In pediatric emergencies, as in case of shock, the use of IO route is recommended to get rapid vascular access as soon as possible, as it revealed better outcome.