Clinical, biochemical, and molecular insights into Cerebrotendinous Xanthomatosis: A nationwide study of 100 Turkish individuals.

OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey. METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed. RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature. CONCLUSION: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

Proinflammatory indicators and the relevance of echocardiography in children with cystic fibrosis.

As the life expectancy improves in cystic fibrosis, cardiac dysfunction is becoming an important risk factor for morbidity and mortality. Here, the association of cardiac dysfunction with proinflammatory markers and neurohormones between cystic fibrosis patients and healthy children was investigated. Echocardiographic measurements of right and left ventricular morphology and functions together with levels of proinflammatory markers and neurohormones (renin, angiotensin-II, and aldosterone) were obtained and analysed in a study group of 21 cystic fibrosis children aged 5-18 years and compared with age- and gender-matched healthy children. It was shown that patients had significantly higher interleukin-6, C-reactive protein, renin and aldosterone levels (p < 0.05), dilated right ventricles, decreased left ventricle sizes, as well as both right and left ventricular dysfunction. These echocardiographic changes correlated with hypoxia, interleukin-1 α, interleukin-6, C-reactive protein, and aldosterone (p < 0.05) levels. The current study revealed that hypoxia, proinflammatory markers, and neurohormones are major determinants of subclinical changes in ventricular morphology and function. While the right ventricle anatomy was affected by cardiac remodeling, the left ventricle changes were induced by right ventricle dilation and hypoxia. A significant but subclinical systolic and diastolic right ventricle dysfunction in our patients was associated with hypoxia and inflammatory markers. Systolic left ventricle function was affected by hypoxia and neurohormones. Echocardiography is a reliable and non-invasive method that is used safely in cystic fibrosis children for screening and detection of cardiac anatomical and functional changes. Extensive studies are needed to determine the time and frequency of screening and treatment suggestions for such changes.

Effects of synbiotic supplementation on intestinal microbiota composition in children and adolescents with exogenous obesity: (Probesity-2 trial).

INTRODUCTION: Gut microbiota manipulation may be a potential therapeutic target to reduce host energy storage. There is limited information about the effects of probiotics/synbiotics on intestinal microbiota composition in children and adolescents with obesity. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic on intestinal microbiota composition in children and adolescents with exogenous obesity. METHOD: Children with exogenous obesity were managed with a standard diet and increased physical activity and were randomly allocated into two groups at a ratio of 1:1; the 1st group received synbiotic supplementation (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus. rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium (total 2.5 × 109 CFU/sachet) and fructo-oligosaccharides (FOS; 625 mg/sachet) for 12 weeks; the 2nd group received placebo once daily for 12 weeks. Fecal samples were obtained before and at the end of the 12-week intervention to characterize the changes in the gut microbiota composition. Detailed metagenomic and bioinformatics analyses were performed. RESULTS: Before the intervention, there were no significant differences in alpha diversity indicators between the synbiotic and placebo groups. After 12 weeks of intervention, the observed taxonomic units and Chao 1 were lower in the synbiotic group than at baseline (p < 0.001 for both). No difference for alpha diversity indicators was observed in the placebo group between baseline and 12 weeks of intervention. At the phylum level, the intestinal microbiota composition of the study groups was similar at baseline. The major phyla in the synbiotic group were Firmicutes (66.7%) and Bacteroidetes (18.8%). In the synbiotic group, the Bacteroidetes phylum was higher after 12 weeks than at baseline (24.0% vs. 18.8%, p < 0.01). In the synbiotic group, the Firmicutes/Bacteroidetes ratio was 3.54 at baseline and 2.75 at 12 weeks of intervention (p < 0.05). In the placebo group, the Firmicutes/Bacteroidetes ratio was 4.70 at baseline and 3.54 at 12 weeks of intervention (p < 0.05). After 12 weeks of intervention, the Firmicutes/Bacteroidetes ratio was also lower in the synbiotic group than in the placebo group (p < 0.05). In the synbiotic group, compared with the baseline, we observed a statistically significant increase in the genera Prevotella (5.28-14.4%, p < 0.001) and Dialister (9.68-13.4%; p < 0.05). Compared to baseline, we observed a statistically significant increase in the genera Prevotella (6.4-12.4%, p < 0.01) and Oscillospira (4.95% vs. 5.70%, p < 0.001) in the placebo group. In the synbiotic group, at the end of the intervention, an increase in Prevotella, Coprococcus, Lachnospiraceae (at the genus level) and Prevotella copri, Coprococcus eutactus, Ruminococcus spp. at the species level compared to baseline (predominance of Eubacterium dolichum, Lactobacillus ruminis, Clostridium ramosum, Bulleidia moorei) was observed. At the end of the 12th week of the study, when the synbiotic and placebo groups were compared, Bacteroides eggerthi species were dominant in the placebo group, while Collinsella stercoris species were dominant in the synbiotic group. CONCLUSION: This study is the first pediatric obesity study to show that a synbiotic treatment is associated with both changes intestinal microbiota composition and decreases in BMI. Trial identifier: NCT05162209 (www. CLINICALTRIALS: gov).

Three-Country Snapshot of Ornithine Transcarbamylase Deficiency.

X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK. Thirty-nine centres responded and 495 patients were reported in total. A total of 208 French patients were reported, including 71 (34%) males, 86 (41%) symptomatic and 51 (25%) asymptomatic females. Eighty-five Turkish patients included 32 (38%) males, 39 (46%) symptomatic and 14 (16%) asymptomatic females. Out of the 202 UK patients, 66 (33%) were male, 83 (41%) asymptomatic and 53 (26%) symptomatic females. A total of 19%, 12% and 7% of the patients presented with a neonatal-onset phenotype in France, Turkey and the UK, respectively. Vomiting, altered mental status and encephalopathy were the most common initial symptoms in all three countries. While 69% in France and 79% in Turkey were receiving protein restriction, 42% were on a protein-restricted diet in the UK. A total of 76%, 47% and 33% of patients were treated with ammonia scavengers in Turkey, France and the UK, respectively. The findings of our audit emphasize the differences and similarities in manifestations and management practices in three countries.

Evaluation of ketogenic diet therapy in children diagnosed with drug-resistant epilepsy: a single-center experience.

BACKGROUND: We evaluate here the effect of the ketogenic diet (KD) on children with drug-resistant epilepsy (DRE) in terms of clinical effectiveness, anthropometric measurements, and some electroencephalogram (EEG) and biochemical findings. METHODS: Included in the study were 18 children (median age 70 months, 61.1% female) who received the classical KD and modified Atkins diet (MAD) for at least one year due to DRE. The patients` demographic and laboratory data; weight, height and body mass index values; EEG and electrocardiographic findings; abdominal ultrasonography findings; and biochemical parameters were recorded at baseline and at 12 months after the initiation of the diet. A reduction of ≥50% in the number of seizures was accepted as a response to KD. RESULTS: Classic KD was chosen for 14 patients (77.8%), and MAD for four patients (22.2%). The response to KD therapy (≥50% reduction) was 55.5% (n = 10) (p = 0.008), and one patient even became seizure-free. By the 12th month of treatment, 10 patients had experienced a reduction of more than 50% in epileptiform discharges, as indicated by EEG findings. There was no difference in seizure reduction between the patients who received classical KD and MAD. A total of 11.1% of the children lost weight during KD treatment. The most common side effect was constipation (n = 10, 55.6%). At the end of one year of treatment, total cholesterol and low density lipoprotein cholesterol (LDL-C) LDL-C levels had increased dramatically, while fasting blood glucose levels had decreased significantly. CONCLUSIONS: Our study suggests that KD treatment provides good clinical efficacy in the treatment of pediatric DRE, and can significantly reduce the frequency of epileptic discharges. Also, total cholesterol and LDL-C levels increased significantly, and fasting blood glucose levels decreased significantly compared to the baseline levels.

Effects of Multispecies Synbiotic Supplementation on Anthropometric Measurements, Glucose and Lipid Parameters in Children With Exogenous Obesity: A Randomized, Double Blind, Placebo-Controlled Clinical Trial (Probesity-2 Trial).

Studies on the effects of synbiotics on obesity in children are limited. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic during 12 weeks on anthropometric measurements, glucose metabolism and lipid parameters in 61 children with exogenous obesity. All children were treated with a standard diet and increased physical activity and received once daily a synbiotic supplement (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium and fructo-oligosaccharides) or daily placebo for 12 weeks. At baseline, no statistically significant differences existed in anthropometric measurements, glucose and lipid parameters between both groups. We observed changes for anthropometric measures (% reduction comparing to baseline) in both synbiotic and placebo groups. After 12 weeks; changes (% reduction comparing to baseline) in weight (p < 0.01), BMI (p < 0.05), waist circumference (p < 0.05) and waist circumference to height ratio (p < 0.05) were significantly higher in the children receiving the synbiotic supplement. There is no difference in glucose metabolism, lipid parameters, presence of non-alcoholic fatty liver disease between both groups after 12 weeks. The daily intake of a multispecies synbiotic in addition to diet and increased physical activity did improve anthropometric measurements: body weight, BMI, waist circumference and waist/height ratio. The supplementation of this synbiotic is an efficient weight-loss strategy above diet and exercise in pediatric obesity (Trial identifier: NCT05162209).

Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey.

OBJECTIVES: The aim of our study was to define the genotype-phenotype correlations of mutations in the PAH gene among the Turkey's Central Anatolian region. METHODS: Demographic characteristics of 108 patients with hyperphenylalaninemia (HPA) and 94 patients whose diagnosis was confirmed by PAH gene analysis (Sanger DNA Sequence Analysis and Next-Generation Sequencing) were determined retrospectively. Blood phenylalanine levels were analyzed using the high-performance liquid chromatography method. RESULTS: Mild HPA-not-requiring-treatment (NT) was found in 50.9% of the patients, and a classical phenylketonuria (PKU) phenotype was found in 25.9%. Forty-seven types of variants were identified. The predominant variants were p.Ala403Val (9.9%), p.Ala300Ser (9.4%), and c.1066-11G>A (splicing) (9.4%). Missense mutations accounted for 68% of mutations and attenuated the clinical impact; splice variations were found in 14.8% of cases with severe features. The p.Thr380Met allele was specific to the mild HPA-NT group. The c.1066-11G>A (splicing) allele was associated with classical PKU, whereas the p.Arg408Trp allele was linked to severe symptoms. Three variations of unknown clinical significance were discovered: c.706+4A>T (splicing), c.843-5T>C (splicing), and p.Thr323=. Of these variants, the patient who was homozygous for the c.843-5T>C (splicing) allele related to the classical PKU phenotype. 70% of the patients who underwent tetrahydrobiopterin (BH4) test were responsive. Phenotypes that responded to BH4 treatment were mostly mild phenotypes. CONCLUSIONS: The PAH genotype is the main factor that determines the phenotype of PKU. Establishing the relationship between the identified genetic mutations and phenotypic characteristics will provide very important data for each patient in terms of the specific management style.

Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability.

OBJECTIVES: To reveal the different clinical presentations of liver glycogen storage disease type IX (GSD IX), which is a clinically and genetically heterogeneous type of glycogenosis. METHODS: The data from the electronic hospital records of 25 patients diagnosed with liver GSD IX was reviewed. Symptoms, clinical findings, and laboratory and molecular analysis were assessed. RESULTS: Of the patients, 10 had complaints of short stature in the initial presentation additionally other clinical findings. Elevated serum transaminases were found in 20 patients, and hepatomegaly was found in 22 patients. Interestingly, three patients were referred due to neurodevelopmental delay and hypotonia, while one was referred for only autism. One patient who presented with neurodevelopmental delay developed hepatomegaly and elevated transaminases during the disease later on. Three of the patients had low hemoglobin A1C and fructosamine values that were near the lowest reference range. Two patients had left ventricular hypertrophy. Three patients developed osteopenia during follow-up, and one patient had osteoporosis after puberty. The most common gene variant, PHKA2, was observed in 16 patients, 10 variants were novel and six variants were defined before. Six patients had variants in PHKG2, two variants were not defined before and four variants were defined before. PHKB variants were found in three patients. One patient had two novel splice site mutations in trans position. It was revealed that one novel homozygous variant and one defined homozygous variant were found in PHKB. CONCLUSIONS: This study revealed that GSD IX may present with only hypotonia and neurodevelopmental delay without liver involvement in the early infantile period. It should be emphasized that although liver GSDIX is thought of as a benign disease, it might present with multisystemic involvement and patients should be screened with echocardiography, bone mineral densitometry, and psychometric evaluation.

Skin closure at cesarean section, polypropylene versus polyglactin 910: a randomized controlled study.

AIM: To compare the rates of surgical wound infection in women who have undergone cesarean delivery with subcuticular skin closure with polyglactin 910 or polypropylene. METHODS: Between April 2018 and October 2018, patients who had undergone a cesarean delivery for any reason were randomized with polyglactin 910 or polypropylene for subcuticular skin closure. Participants were evaluated for wound complications on day 7 and 30 postoperatively. The primary outcome was surgical site infection within the first 30 days following delivery. In addition, factors affecting surgical site infections were analyzed by binary regression. RESULTS: A total of 220 women who had undergone cesarean delivery were randomized and 213 were included in the final analysis. The groups were similar in terms of demographic characteristics and perioperative features. No statistically significant difference was observed between the groups in terms of wound complications or superficial site infections (8.3% in the polypropylene group versus 10.6% in the polyglactin 910 group, p = .642). Similarly, no difference was observed between the groups in terms of other wound complications. A binary logistic regression analysis indicated that superficial wound site infection was not affected by gravidity, BMI, duration of operation, repeated or unplanned cesarean delivery. CONCLUSION: It was observed that surgical site infections and other wound complications in skin closures with polyglactin 910 were similar to those with polypropylene.

Evaluation of micronutrient levels in children with cerebral palsy.

BACKGROUND: Many studies evaluating the nutritional status of children with cerebral palsy (CP) have focused on energy requirements and protein intake. The present work aimed to assess nutritional status and micronutrient levels of children with (CP). METHODS: This multicenter, cross-sectional and observational study was conducted in 10 different cities in Turkey. Data were available for 398 participants. Anthropometric measurements, feeding mode, nutritional status, and micronutrient levels were evaluated. RESULTS: The study was conducted with 398 participants (303 patients and 95 healthy controls). Statistical analysis showed that according to the Gomez Classification, weight-for-age (WFA) revealed malnutrition in 92.6% of children with CP, based on Centers for Disease Control and Prevention percentiles. Measurements of micronutrient levels showed that zinc levels were low in patients, whereas vitamin A levels were low in controls. Phosphorous and manganese levels were significantly lower in malnourished children than in typical children. The results revealed that children consuming enteral nutrition solutions had higher selenium and lower zinc levels than non-consumers. CONCLUSIONS: Malnutrition is not only a protein- or calorie-based problem; micronutrient deficiencies might cause severe health problems. Children with chronic neurological disabilities must be carefully evaluated for these issues. Therefore, nutritional interventions should be adapted to nutrition.

Niemann-Pick type C disease with a novel intronic mutation: three Turkish cases from the same family.

OBJECTIVES: Niemann-Pick type C (NPC) disease is a rare progressive neurodegenerative condition that is characterized by the accumulation of cholesterol, glycosphingolipids, and sphingosine in lysosomes. Patients have various systemic and neurological findings depending on their age at onset. This disease is caused by the autosomal recessive transmission of mutations in the NPC1 and NPC2 genes; patients have mutations mainly in the NPC1 gene (95%) and the majority of them are point mutations located in the exonic regions. CASE PRESENTATION: Here, we presented three cousins with hepatosplenomegaly and progressive neurodegeneration who were diagnosed with visceral-neurodegenerative NPC disease. Their parents were relatives, and they had a history of sibling death with similar complaints. Bone marrow smear showed foamy cells in patient 1. Vertical supranuclear gaze palsy was not present in all cases. Sphingomyelinase (SM) activities were almost normal to exclude NPA or NPB. Filipin staining was performed in patient 2 and showed a massive accumulation of unesterified cholesterol The NPC1 gene analysis of the three patients showed a novel homozygous c.1553+5G>A intronic mutation. cDNA analysis was performed from the patient 3 and both parents. It was observed that exon 9 was completely skipped in the homozygous mutant baby. Both the normal and the exon 9-skipped transcripts have been detected in the parents. CONCLUSIONS: When combined with the filipin staining and the patients' clinical outcomes, this mutation is likely to be deleterious. Moreover, cDNA sequencing supports the pathogenicity of this novel variant.

Assessment of respiratory tract viruses in febrile neutropenic etiology in children and comparison with healthy children with upper/lower respiratory tract infection.

OBJECTIVE: This study aims to compare the frequency of respiratory viruses using real-time and multiplex polymerase chain reaction technology and nasopharyngeal swabs taken during exacerbation of patients aged 0-18 years followed for febrile neutropenia (FN) with non-FN children. METHODS: This prospective study included a total of 40 patients with FN and malignancies followed at Eskisehir Osmangazi University, Department of Pediatric Hematology and Oncology. The control group (n=76) consisted of age-matched patients with upper respiratory tract infections (URTIs) or lower respiratory tract infections (LRTIs) who were admitted to the emergency service due to fever. RESULTS: Viral agents were detected in 16 of 53 FN attacks (30.1%). The most commonly isolated viruses were coronavirus (23.7%, n=9), influenza B (18.4%, n=7), and adenovirus (18.4%, n=7). Of 76 children diagnosed with URTI with fever (52.6%) had viral agents, and only 28 of them had a single agent. The most commonly isolated virus was adenovirus (28.6%, n=14). Viral factors were found in 32 of 42 patients (76.1%) patients diagnosed with LRTI, while respiratory syncytial virus was the most common virus in 27 patients (21.7%, n=5). CONCLUSION: Our study results show that viral agents play an important role in the etiology of FN. This is the first study to show that viral agents play an important role in the etiology of this disease and viral factors in non-neutropenic febrile children at the same time period by detecting respiratory viruses in 30% of FN cases. More similar studies provide antiviral therapy in selected patients, as well as these studies lead to reduce the use of antimicrobial agents or allow more selective use of antibiotics and/or the earlier discontinuation of these antibiotics in febrile neutropenic children who have been shown to have viral cause of respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria.

Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients.

Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. In this cross-sectional, multicenter, descriptive study, medical records of 66 AKU patients were retrospectively evaluated. Patients' data regarding demographic, clinical and genetic characteristics were recorded. HGD database (http://hgddatabase.cvtisr.sk/) was used to identify HGD gene variants. Of the patients, 37 (56.1%) presented with isolated dark urine and 29 (43.9%) were diagnosed based on the clinical symptoms or family screening. One of these patients was on follow-up for 2 years due to Parkinsonism and was diagnosed with AKU on further analyses. Signs of ochronosis such as joint pain, low back pain and renal stones developed in childhood in 7 patients. Eight patients were diagnosed with depression via psychiatric evaluation. There were 14 (21.2%) patients operated on for ochronosis. The most frequent mutation observed in the patients was c.175delA, which was followed by c.674G > A and c.1007-2A > T mutations. Four novel mutations (c.189G > A, c.549+1G > T, c.1188+1G > A, and c.334 T > G) were identified in the patients included in the study. In addition to the known signs such as dark urine and skin pigmentation, symptoms involving different systems such as neurological findings and depression can also be encountered in AKU patients. The presence of a change in urine color needs to be questioned in patients presenting with different symptoms such as arthralgia/arthritis, renal stones or low-back pain, particularly in childhood, when skin ochronosis is not pronounced, and further examination should be performed.

Patients with cerebrotendinous xanthomatosis diagnosed with diverse multisystem involvement.

Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by deficiency of sterol 27-hydroxylase enzyme encoded by CYP27A1 gene. This multicenter, cross-sectional descriptive study aimed to document clinical characteristics of CTX patients of different ages, clinical presentations of early-diagnosed patients, and responses to short-term chenodeoxycholic acid (CDCA) treatment. Seven of 11 CTX patients were diagnosed in childhood. Three patients (27%) had neonatal cholestasis, seven (63%) patients had a history of frequent watery defecation started in infantile period, and eight (72.7%) patients had juvenile cataract. Four patients in the adult age group had pyramidal signs and parkinsonism symptoms. The mean Mignarri score at diagnosis was significantly lower in the pediatric patients (267.8 ± 51.4) than in the adult patients (450.0 ± 64.0, p = 0.001). No significant difference was determined between pediatric patients and adult patients regarding plasma cholestanol concentration at diagnosis (p = 0.482). The frequency of defecation decreased with treatment in six children, who had diarrhea at admission. Compared to pretreatment values, patients' body weight and standardized body mass index significantly increased at the 12th month of treatment. In conclusion, Mignarri scores are lower in the pediatric patients than in adult patients since the most determinative signs of the CTX disease are not apparent yet in the childhood. The disease is frequently overlooked in routine practice as the disease presents itself with different clinical combinations both in adults and in children. CTX is potentially a treatable disease; thereby, enhanced awareness is critically important for early diagnosis particularly in children.

Social Jetlag Is Associated with the Frequency of Consumption of Sugar-Sweetened Beverages and a High BMI Percentile in Adolescents: Results of the Cross-Sectional Family Life, Activity, Sun, Health, and Eating (FLASHE) Study.

BACKGROUND: Social jetlag (SJL) occurs in adolescents due to misalignment of the biological and social clocks, so that most teens wake up earlier than their biological clocks on weekdays and delay bedtime and wake up time on weekends. This shift in sleep timing among adolescents is associated with an adverse endocrine and behavioral risk profile, in addition to increased food consumption and increased body mass index (BMI). OBJECTIVE: The aim of this study was to determine the association between SJL, and the frequency of consumption of multiple food and beverage groups and BMI percentile in adolescents. DESIGN: Publicly available data from the cross-sectional Family Life, Activity, Sun, Health, and Eating (FLASHE) study were analyzed. PARTICIPANTS: Participants from the FLASHE study were recruited from all regions of the United States between April and October 2014. Among the 1,581 adolescents aged 12 through 17 years in the original study, 1,556 with complete sleep data were analyzed. MAIN OUTCOME MEASURES: The difference between the frequency of dietary consumption according to the Dietary Screener Questionnaire and BMI percentile was assessed in adolescents grouped according to SJL, as follows: no SJL: less than 1-hour difference; mild SJL: 1- to 2-hour difference; and severe SJL: more than 2-hour difference. STATISTICAL ANALYSES PERFORMED: Differences in the frequency of food consumption were analyzed using the Kruskal-Wallis test. Secondary outcomes were analyzed using logistic regression models. RESULTS: Daily consumption frequency of sugar-sweetened beverages and fruits and vegetables differed among the 3 groups. Likewise, the BMI percentile differed among the 3 groups and was highest in the severe SJL group. Those in the severe SJL group had a 1.84-fold higher probability of having overweight or obesity (95% CI 1.83 to 1.84) than those in the no SJL group. CONCLUSIONS: Severe SJL is associated with a higher frequency of sugar-sweetened beverage consumption and higher odds of having overweight or obesity compared with no SJL in adolescents.

What is new in peripartum hysterectomy? A seventeen year experience in a tertiary hospital.

OBJECTIVE: To identify changing trends in peripartum hysterectomy (PH), both elective. cesarean hysterectomy and emergency cesarean hysterectomy, at a single training and research hospital over the last 17 years in Istanbul, Turkey. MATERIALS AND METHODS: A retrospective cohort study was performed between January 2001 and September 2017. The records of all patients who had PH at Kanuni Sultan Süleyman Training and Research Hospital were analyzed. RESULTS: There were 243 cases of PH during the study period. A total of 266,386 births occurred, of which 60.1% were vaginal deliveries and 39.8% were cesarean sections. The incidence of PH increased from 0.67 per 1000 deliveries to 1.14 per 1000 deliveries during 2001-2008 and 2009-2017, respectively, with an overall incidence of 0.91 per 1000 deliveries during the 17 years. The main indication for PH changed significantly during this time from uterine atony (57.1%) to placenta accreta spectrum (85%). About 37% of women who underwent PH had at least one previous cesarean delivery during 2001-2008, whereas that percentage increased to 95.4% during 2009-2017. CONCLUSION: Placenta accreta spectrum was the leading cause of PH and was associated with significant maternal morbidity and mortality.

The association of lipid metabolism and non-alcoholic fatty liver disease in children with obesity.

AIM: Obesity, insulin resistance, and hyperlipidemia have been shown as risk factors for non-alcoholic fatty liver disease. In this study, the association between lipid and lipoprotein metabolism abnormalities and the presence of non-alcoholic fatty liver disease was investigated in patients with obesity. MATERIAL AND METHODS: In this study, the clinical, laboratory and imaging findings of 357 children and adolescent patients (199 girls and 158 boys) aged 2-18 years who were diagnosed as having obesity between 2013 and 2018 were retrospectively analyzed. The clinical and laboratory features of the patients who were diagnosed as having non-alcoholic fatty liver disease using ultrasonography were compared with patients who did not have non-alcoholic fatty liver disease. All lipid and lipoprotein levels were defined as hypo-, normo- and hyperlipidemic in comparison with the reference values according to age and sex. RESULTS: The frequency of non-alcoholic fatty liver disease was 44.5% in the entire study group and was higher in males (p<0.05). The body weight, body mass index, alanine aminotransferase, glucose, insulin, non-high-density lipoprotein-cholesterol, and HOMA-IR scores were found to be higher in the patients with non-alcoholic fatty liver disease, whereas the high-density lipoprotein-cholesterol level was lower (p<0.05). There was no difference in the frequency of non-alcoholic fatty liver disease among the patients with low, normal, and high total cholesterol, triglyceride and low-density lipoprotein-cholesterol levels (p>0.05). The frequency of lipid metabolism disorder (hypolipidemia and/or hyperlipidemia) was found as 77.5% in all patients. CONCLUSION: Non-alcoholic liver disease and lipid metabolism disorders are common in children and adolescents with obesity. The frequency of non-alcoholic fatty liver disease in hypolipidemic, normolipidemic, and hyperlipidemic patients was not different. This finding indicated that the increase in the amount of body fatty tissue and insulin resistance were more important risk factors in the development of non-alcoholic fatty liver disease.

Analysis of the alpha galactosidase gene: mutation profile and description of two novel mutations with extensive literature review in Turkish population.

Objectives Fabry disease (FD, OMIM #301500) is a rare and progressive X-linked lysosomal storage disorder. FD is caused by mutations in the GLA gene on chromosome Xq22. Methods In this article, we aimed to present the largest sample of GLA mutation spectrum including common and novel variants in Turkish population. GLA gene sequence analysis was performed on the subjects who applied to the department of medical genetics with the preliminary diagnosis of FD between 2013 and 2018. Results We detected 22 different mutations as two novel [(p.F69S(c.206T>C), p.P205A (c.613C>G)] and 20 previously reported GLA mutations in 47 individuals from 22 unrelated families. These mutations included 14 missense mutations, four nonsense mutations, two small deletions, one small deletion/insertion and one small insertion. Major clinical findings of the female case with p.F69S(c.206T>C) mutation were cornea verticillata, acroparesthesia, angiokeratoma, psychiatric and gastrointestinal symptoms. Other novel mutation (p.P205A [c.613C>G]) was carried by a male case presenting gastrointestinal symptoms. Conclusions We described clinical findings of two cases that had novel mutations to provide more insight in genotype-phenotype correlation. We presented the largest mutation spectrum in Turkish population and reviewed previous mutations in this article.

Sudden cardiac arrest during induction of anaesthesia in paediatric patient with glutaric aciduria type II.

Glutaric aciduria type II (GA2) is an autosomal recessive metabolic disorder of amino acid and lipid metabolism, which is serious and rare. The most serious form is seen in early infancy and is associated with very high mortality rates. Here, we present an 8-month-old male patient with GA2 who had electrocardiographic ST ST-segment depression and sudden cardiac arrest at 10th minute of emergency operation (central venous catheter placement). There is a very scarce amount of data in the literature about anaesthetic management of GA2 patients. There is also no previously published report about cardiac arrest during induction of anaesthesia in this condition. The present report highlights this serious complication.

A severe course of serogroup W meningococcemia in a patient with infantile nephropathic cystinosis.

We present a 9-month old boy with cystinosis admitted to our hospital with the complaints of vomiting, diarrhea and seizure. While he was hospitalized in a pediatric intensive care unit due to worsening of his signs related to cystinosis, within hours, he suffered complications of septic shock, acute renal failure, and disseminated intravascular coagulation, due to invasive Neisseria meningitidis serogroup W disease. Our patient is the first reported case of invasive meningococcal disease with cystinosis. Clinicians should consider that the unexpected and serious clinical findings of invasive meningococcal disease can mimic and/or masquerade as other metabolic diseases. Vaccination strategies, according to serogroup epidemiology and age distribution, should be implemented for the prevention of meningococcal infections.