A case report of an Egyptian family with familial hypercholesterolemia and an exonic LINE-1 insertion in LDLR.

BACKGROUND: Familial hypercholesterolemia (MIM: PS143890) is a genetic disorder characterized by an increase in blood cholesterol. LDLR is one of the genes which their defect contributes to the disorder. Affected individuals may carry a heterozygous variant or homozygous/compound heterozygous variants and those with biallelic pathogenic variants present more severe symptoms. METHOD: We report an Egyptian family with familial hypercholesterolemia. Both the proband and parents have the disorder while a sibling is unaffected. Exome sequencing was performed to identify the causal variant. RESULTS: LINE-1 insertion in exon 7 of LDLR was identified. Both parents have a heterozygous variant while the proband has a homozygous variant. The unaffected sibling did not carry the variant. DISCUSSION: This insertion may contribute to the high prevalence of hypercholesterolemia in Egypt and the finding underscores the importance of implementing mobile element insertion caller in routine bioinformatics pipeline.

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.

The malnutrition screening tool STRONGKIDS performed better than other screening tools for children hospitalised in Egypt.

AIM: To compare the accuracy of three different screening tools, namely, the Paediatric Yorkhill Malnutrition Score (PYMS), Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP), and Screening Tool for Risk on Nutritional Status and Growth (STRONGKIDS), in assessing malnutrition risk in hospitalised children. METHODS: A cross-sectional study was conducted on 300 children aged 6 months to 15 years at Alexandria University Children's Hospital, Egypt. The sensitivity and specificity of each tool were calculated to detect acute and chronic malnutrition, and an agreement test was conducted between the nutritional screening tools. The patients were classified into different nutritional risk groups, and their classification was compared with anthropometric measures and clinical variables, such as the length of hospital stay (LOS). RESULTS: The prevalence of stunting and wasting on admission was found to be 3% and 6.6%, respectively. Children categorised as high-risk on admission had a longer LOS than those at low risk. The agreement test between the STAMP score and STRONGKIDS score on admission showed the most significant agreement, and STRONGKIDS had the best accuracy in detecting acute and chronic malnutrition. CONCLUSION: The comparison of the three screening tools revealed that STRONGKIDS exhibited the best accuracy in detecting acute and chronic malnutrition.

Evaluation of non-thyroidal illness syndrome in shock patients admitted to pediatric intensive care unit in a developing country.

During critical illness, children my experience various changes in their thyroid hormone levels. Such changes are termed non-thyroidal illness syndrome (NTI). The extent of change correlates with the severity of the illness and its outcomes in critically ill patients. This study aimed to investigate the correlation between the severity of shock and thyroid hormone derangement. This prospective observational study included forty patients aged one month to five years who were admitted to the pediatric intensive care unit (PICU) with shock. Thyroid function tests were conducted on admission, after shock reversal, and five days later. NTI patterns were observed in 70% of patients. The PIM2 score showed a significant negative correlation with T3 (r = - 0.353, p = 0.026) and FT3 levels on admission (r = - 0.417, p = 0.007). Furthermore, after shock reversal, the PIM2 score continued to exhibit significant negative correlations with T4 (r = - 0.444, p = 0.004), T3 (r = - 0.329, p = 0.038), FT3 (r = - 0.355, p = 0.025), and FT4 levels (r = - 0.379, p = 0.016).    Conclusion: This study underscores the high prevalence of NTI in PICU shock patients and suggests monitoring thyroid hormone levels for outcome prediction and treatment guidance. Further research is needed to optimize NTI management in critically ill children. What is Known: • Non-thyroidal illness syndrome (NTIS) is a condition observed in critically ill patients. • There has been limited research on NTI in children, and existing studies have generated conflicting results regarding the relationship between thyroid hormones and clinical outcomes in cases of sepsis and septic shock. What is New: • The study has revealed dynamic changes in free triiodothyronine (FT3) levels during the process of shock reversal and recovery in children who experienced shock. • A significant negative correlation was found between the Pediatric Index of Mortality 2 (PIM2) score and several thyroid hormone levels, including FT3 on admission and T4, FT3, and FT4 on shock reversal.

Cyclin D2 gene variance and expression level in pediatric acute lymphoblastic leukemia.

BACKGROUND: Cyclin D2 (CCND2) is a crucial player in cell cycle regulation. CCND2 polymorphisms contribute to cancer predisposition. OBJECTIVES: To evaluate the association of CCND2 rs3217927 single nucleotide polymorphisms (SNP) and its expression levels with acute lymphoblastic leukemia (ALL) susceptibility in Egyptian children and its potential prognostic role. METHODS: The 5' nuclease allelic discrimination assay was used to evaluate the frequency of CCND2 rs3217927 SNP in 80 newly diagnosed children with ALL and 80 age- and sex-matched controls. CCND2 relative expression levels were determined by real-time quantitative polymerase chain reaction. RESULTS: The genotype analysis revealed that the GG genotype and G allele were significantly more prevalent among ALL patients than controls (p Ë‚ .001). Regression analysis demonstrated that Egyptian children carrying only one G allele had about 31-fold increased risk to develop ALL compared to A allele carriers. CCND2 was overexpressed in ALL patients compared to controls (p < .001). The CCND2 overexpression was associated with the GG genotype and G allele (p < .001). Furthermore, G allele was an independent negative prognostic marker for central nervous system (CNS) involvement (odds ratio [OR] = 4.676; 95% confidence interval [CI]: 1.2-18.6), risk stratification (OR = 38; 95% CI: 7.7-188.2), and chemoresistance (OR = 9.864; 95% CI: 5.6-70.3) in ALL patients. CONCLUSIONS: G allele of CCND2 rs3217927 SNP might be associated with increased risk for ALL in Egyptian children besides being an independent negative prognostic marker for their risk stratification and therapeutic outcome. CCND2 rs3217927 SNP genotyping might be used to demarcate ALL patients with aggressive disease phenotypes who may be candidate for alternative targeted therapeutic strategies.

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.

Clinically Relevant KCNQ1 Variants Causing KCNQ1-KCNE2 Gain-of-Function Affect the Ca2+ Sensitivity of the Channel.

Dominant KCNQ1 variants are well-known for underlying cardiac arrhythmia syndromes. The two heterozygous KCNQ1 missense variants, R116L and P369L, cause an allelic disorder characterized by pituitary hormone deficiency and maternally inherited gingival fibromatosis. Increased K+ conductance upon co-expression of KCNQ1 mutant channels with the beta subunit KCNE2 is suggested to underlie the phenotype; however, the reason for KCNQ1-KCNE2 (Q1E2) channel gain-of-function is unknown. We aimed to discover the genetic defect in a single individual and three family members with gingival overgrowth and identified the KCNQ1 variants P369L and V185M, respectively. Patch-clamp experiments demonstrated increased constitutive K+ conductance of V185M-Q1E2 channels, confirming the pathogenicity of the novel variant. To gain insight into the pathomechanism, we examined all three disease-causing KCNQ1 mutants. Manipulation of the intracellular Ca2+ concentration prior to and during whole-cell recordings identified an impaired Ca2+ sensitivity of the mutant KCNQ1 channels. With low Ca2+, wild-type KCNQ1 currents were efficiently reduced and exhibited a pre-pulse-dependent cross-over of current traces and a high-voltage-activated component. These features were absent in mutant KCNQ1 channels and in wild-type channels co-expressed with calmodulin and exposed to high intracellular Ca2+. Moreover, co-expression of calmodulin with wild-type Q1E2 channels and loading the cells with high Ca2+ drastically increased Q1E2 current amplitudes, suggesting that KCNE2 normally limits the resting Q1E2 conductance by an increased demand for calcified calmodulin to achieve effective channel opening. Our data link impaired Ca2+ sensitivity of the KCNQ1 mutants R116L, V185M and P369L to Q1E2 gain-of-function that is associated with a particular KCNQ1 channelopathy.

Effect of early feeding practices and eating behaviors on body composition in primary school children.

BACKGROUND: Understanding children's feeding practices and eating behaviors is important to determine etiology of childhood obesity. This study aimed to explore the relationship between early feeding practices, eating behavior and body composition among primary school children. METHODS: The data were collected from 403 primary school children. They were administered structured questionnaire, including sociodemographic characteristics, early feeding practices and Child's Eating Behavior Questionnaire. Anthropometric and blood pressure (BP) measurements were performed. RESULTS: Children with obesity and overweight showed higher food approach subscales and lower food avoidance subscales compared to a healthy and underweight child. Children who were exclusively or predominantly breast fed during the first 6 months had the lowest scores for the food approach subscales, food responsiveness (FR) and emotional overeating (EOE) and had the highest scores for the food avoidance subscales, satiety responsiveness (SR) and emotional under eating (EUE). Children who were introduced solid food after 6 months showed lower scores for FR, enjoyment of food and EOE but scored highest for SR, slowness in eating (SE) and EUE. All anthropometric measurements were positively correlated with all food approach subscales and negatively with SE, SR and food fussiness. All food approach subscales were positively correlated with BP percentiles. All food avoidance subscales were negatively correlated with both BP percentiles, except for EUE, which was negatively correlated with diastolic BP percentile only. Age, SR, SE and FR were predictors for child body mass index. CONCLUSION: Early feeding practices and eating behavior are considered as prevention approaches for obesity.

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.

Sensory Processing and Gastrointestinal Manifestations in Autism Spectrum Disorders: No Relation to Clostridium difficile.

The role of the gut microbiota in triggering autism is a rapidly emerging field of research. Gut microbiota have been incriminated because autistic children often have gastrointestinal symptoms. Pathogenic gut bacteria in children with autism spectrum disorders (ASD) have been reported. The present study aimed to assess Clostridium difficile in the stool of children with ASD and its relation to gastrointestinal (GI) comorbidities, autism severity, and sensory impairment. The study included 58 ASD patients, 45 of their neurotypical siblings, and 45 unrelated controls. Childhood Autism Rating Scale (CARS) was used to assess the severity of autism. Sensory problems were evaluated using the Short Sensory Profile (SSP). GI symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire. Quantitative real-time PCR was done for the detection and quantitation of C. difficile and its toxins A and B. C. difficile was detected in 25.9%, 40%, and 15.6% of ASD cases, siblings, and unrelated control respectively. Regarding toxin A and B production, 73.3%, 77.8%, and 71.4% of C. difficile in positive ASD, siblings, and unrelated control cases respectively were toxigenic. There was no statistically significant difference between the three groups as regards C. difficile qualitative, quantitative, and toxin production results. In conclusion, C. difficile is not specifically prevalent in the gut of children with ASD. Although most of the strains are toxigenic, there were no GI symptoms in the control groups and no statistically significant association with GI Severity Index in autistic cases. Gastrointestinal dysfunction and sensory impairment are common comorbidities in ASD.

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.

Bovine Colostrum in the Treatment of Acute Diarrhea in Children: A Double-Blinded Randomized Controlled Trial.

OBJECTIVES: To evaluate the effect of bovine colostrum (BC) on the treatment of children with acute diarrhea attending the outpatient clinic. METHODS: This double-blind randomized controlled trial was conducted on 160 children with diarrhea; 80 cases were randomly treated with BC group and 80 cases randomly received placebo (placebo group). All cases were investigated for bacterial causes of diarrhea (Salmonella spp, Shigella spp, diarrheagenic E. coli (DEC), Campylobacter spp., and Vibrio cholerae) as well as for Rotavirus antigen in stool. RESULTS: After 48 h, the BC group had a significantly lower frequency of vomiting, diarrhea and Vesikari scoring compared with the placebo group (p = 0.000, p = 0.000, p = 0.000, respectively), whether it was due to Rotavirus or E. coli infection. CONCLUSIONS: BC is effective in the treatment of acute diarrhea and can be considered as adjuvant therapy in both viral and bacterial diarrhea to prevent diarrhea-related complications.

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.

Sex assignment practice in disorders of sexual differentiation: survey results from paediatric endocrinologists in the Arab region.

Background Sex assignment is a major issue in disorders of sexual differentiation (DSD). Not all conditions of DSD have clear recommendations on assignment and timing of surgery. Reports about sex assignment practice and the influence of culture and religion in the Arab region are scarce. Methods A survey questionnaire was distributed to participants in a paediatric endocrinology conference. Four DSD cases were presented. Participants were asked to fill in their answers on sex assignment choice, reasons for the particular assignment, strength of own recommendation and timing of surgery based on their practice. The cases presented were severely virilised XX congenital adrenal hyperplasia (CAH), complete androgen insensitivity syndrome (CAIS), severely undervirilised 5α reductase deficiency (5α RD) and XX ovotesticular case. Results Eighty-five endocrinologists participated in the study. Eighty (97.5%) chose a female sex to assign for the XX CAH. For the CAIS, 64 (78%) chose a female sex. Seventy-one (86.5%) voted for a male sex for the XY case of 5α RD. Forty-seven (57%) and 35 (43%) chose a female and a male sex for the ovotesticular case, respectively. The majority indicated that their advice for sex assignment is based on strong recommendations for the CAH, CAIS and 5α RD patients but they were open to the parents' cultural and religious beliefs in their decision of the assignment for the ovotesticular case. Conclusions Practice in the Arab region appears to be in line with the international guidelines in the majority of DSD sex assignment and timing of surgery issues. However, culture and religious beliefs influence the practice in certain circumstances.

A retrospective study of small molecule disorder types of metabolism in paediatric patients in intensive care.

BACKGROUND: Although inborn errors of metabolism (IEM) are rare individually, collectively IEM cause substantial morbidity and mortality and the diagnosis is challenging. AIMS: To analyse epidemiological and clinical data, final diagnosis and clinical outcomes of patients with a suspected diagnosis of IEM (small molecule disorders type) admitted to a paediatric intensive care unit (PICU). METHODS: We collected and analysed medical records data of all patients admitted to the PICU at Alexandria University Children's Hospital, from January 2010 to December 2014, with a suspected or confirmed diagnosis of small molecule disorders, including clinical presentations, laboratory results and clinical outcomes. RESULTS: A total of 34 patients had a suspected or confirmed diagnosis of small molecule disorders at PICU admission. Diagnosis was confirmed in 22.7% of suspected cases at admission and in 25% of suspected cases during PICU stay. Consanguineous marriage was found in 50% of cases with confirmed small molecule disorders. CONCLUSIONS: A high index of suspicion is important for diagnosing and categorizing small molecule disorders in screening of high-risk individuals in low- and middle-income countries.

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.