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.

Experience with cascade screening: A comprehensive family pedigree analysis of two index patients with Fabry disease.

The wide range of clinical symptoms observed in patients with Fabry disease (FD) often leads to delays in diagnosis and initiation of treatment. Delayed initiation of therapy may result in end-organ damage, such as chronic renal failure, hypertrophic cardiomyopathy, and stroke. Although some tools are available to identify undiagnosed patients, new comprehensive screening methods are needed. In this study, the outcomes of the cascade screening applied to three index cases with FD from 2 familes were investigated. In the pedigree analysis, 280 individuals were included; out of them, 131 individuals underwent genetic testing and cascade screening for FD. During the screening program, a total of 45 individuals were diagnosed, with a diagnostic ratio of 1:15. The average age at diagnosis for all individuals was 30.9 ± 17.7 years, and %25 were pediatric cases (mean age 9.5 ± 5.9 years). Thirty affected relatives were diagnosed from the two index cases in Family 1 and 15 individuals were diagnosed from one index case in Family 2. There were 13 consanguineous marriages observed among 2 pedigres, in two both spouses  were affected, leading to two homozygous affected daughters in one couple. In regions where there is a high prevalence of consanguineous marriages, implementing the cascade screening approach to identify all individuals at risk can be beneficial for patients with FD, specifically women and children.

Positive effects of ketogenic diet on weight control in children with obesity due to Prader-Willi syndrome.

OBJECTIVE: Prader-Willi Syndrome (PWS) is the most common genetic cause of obesity. Prevention and management of obesity, which represents the main cause of morbidity and mortality in these patients, is essential. Ketogenic diet (KD) is used in the treatment of various disorders, however knowledge of its effect in PWS is lacking. The present study assesses the characteristics of patients with PWS who were on KD. DESIGN AND PATIENTS: This is a retrospective, cross-sectional descriptive study investigating the subjects with PWS, who had received KD for at least 6 months. RESULTS: Ten patients with PWS [median age 52.5 (47-77) months] complied with KD. The median treatment period was 16.5 [11-52] months. Of the daily calorie, 75%-85% were from fat, and 15%-25% from protein + carbohydrate. The baseline body weight standard deviation (SD) score before diet therapy was 2.10 [-1.11-4.11], whereas it was 0.05 [-0.92-1.2] at final evaluation (p = .007). The baseline median BMI SD score before diet therapy was 3.05 [-0.21-3.72], whereas it was 0.41 [-0.87-1.57] at final evaluation (p = .002). The height SD score remained unchanged. Mild hypercholesterolaemia was the most common biochemical abnormality during treatment with KD. CONCLUSION: Our results indicate that KD might have a favourable effect on weight management in PWS.

High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases.

Consanguineous marriages have a prevalence rate of 24% in Turkey. These carry an increased risk of autosomal recessive genetic conditions, leading to severe disability or premature death, with a significant health and economic burden. A definitive molecular diagnosis could not be achieved in these children previously, as infrastructures and access to sophisticated diagnostic options were limited. We studied the cause of neurogenetic disease in 246 children from 190 consanguineous families recruited in three Turkish hospitals between 2016 and 2020. All patients underwent deep phenotyping and trio whole exome sequencing, and data were integrated in advanced international bioinformatics platforms. We detected causative variants in 119 known disease genes in 72% of families. Due to overlapping phenotypes 52% of the confirmed genetic diagnoses would have been missed on targeted diagnostic gene panels. Likely pathogenic variants in 27 novel genes in 14% of the families increased the diagnostic yield to 86%. Eighty-two per cent of causative variants (141/172) were homozygous, 11 of which were detected in genes previously only associated with autosomal dominant inheritance. Eight families carried two pathogenic variants in different disease genes. De novo (9.3%), X-linked recessive (5.2%) and compound heterozygous (3.5%) variants were less frequent compared to non-consanguineous populations. This cohort provided a unique opportunity to better understand the genetic characteristics of neurogenetic diseases in a consanguineous population. Contrary to what may be expected, causative variants were often not on the longest run of homozygosity and the diagnostic yield was lower in families with the highest degree of consanguinity, due to the high number of homozygous variants in these patients. Pathway analysis highlighted that protein synthesis/degradation defects and metabolic diseases are the most common pathways underlying paediatric neurogenetic disease. In our cohort 164 families (86%) received a diagnosis, enabling prevention of transmission and targeted treatments in 24 patients (10%). We generated an important body of genomic data with lasting impacts on the health and wellbeing of consanguineous families and economic benefit for the healthcare system in Turkey and elsewhere. We demonstrate that an untargeted next generation sequencing approach is far superior to a more targeted gene panel approach, and can be performed without specialized bioinformatics knowledge by clinicians using established pipelines in populations with high rates of consanguinity.

Efficacy of Phenylalanine- and Tyrosine-Restricted Diet in Alkaptonuria Patients on Nitisinone Treatment: Case Series and Review of Literature.

INTRODUCTION: Nitisinone used in alkaptonuria (AKU) can result in keratopathy due to strongly increased tyrosine levels. METHODS: This study aimed to investigate nutritional status and changes in plasma tyrosine and phenylalanine and urinary homogentisic acid (u-HGA) levels in 8 adult AKU patients (mean age, 56.3 ± 4.7 years) who were on tyrosine/phenylalanine-restricted diet together with 2 mg/day nitisinone. RESULTS: The treatment period was 23.4 ± 6.9 months. Daily dietary protein intake was restricted to 0.8-1.0 g/kg/day. Daily tyrosine intake was restricted to 260-450 mg/day for females and 330-550 mg/day for males. Tyrosine/phenylalanine-free amino acid supplements accounted for an average of 56.1% of daily protein intake. The following assessments were performed: anthropometric and plasma tyrosine level measurements every 2 months; ophthalmological examination every 6 months, and nutritional laboratory analyses and measurements of plasma amino acids and u-HGA once in a year. It was targeted to keep the plasma tyrosine level <500 µmol/L. The plasma tyrosine level was <100 µmol/L before the treatment in all patients and around a mean of 582.5 ± 194.8 µmol/L during the treatment. The diet was rearranged if a plasma tyrosine level of >700 µmol/L was detected. The u-HGA level before and after the 1st year of treatment was 1,429.3 ± 1,073.4 mmol/mol creatinine and 33.6 ± 9.5 mmol/mol creatinine, respectively. None of the patients developed keratopathy or experienced weight loss and protein or micronutrient deficiency. CONCLUSION: AKU patients should receive tyrosine/phenylalanine-restricted diet for reducing plasma tyrosine level to the safe range. Tyrosine/phenylalanine-free amino acid supplements can be safely used to enhance dietary compliance. Keratopathy and nutrient deficiency should be frequently monitored.

Could lysosomal acid lipase enzyme activity be used for clinical follow-up in cryptogenic cirrhosis?

BACKGROUND: Cholesterol ester storage disease (CESD) is one of the rare causes that should be kept in mind in the etiology of cirrhosis. Recent studies detected that significantly reduced lysosomal acid lipase deficiency enzyme (LAL) in patients with cryptogenic cirrhosis (CC). Moreover, studies have evaluated that LAL activity is as effective as scoring systems in assessing the severity of cirrhosis. In this study, we aimed to investigate the CESD with LAL level and mutation analysis of LIPA gene in patients diagnosed with CC and to compare LAL activities between patients with CC and healthy volunteers. METHODS: Laboratory parameters and cirrhosis stage (CHILD and MELD) were recorded for the patient group included in the study. In addition, blood samples were taken from each case included in the study for LAL activity determination and LIPA gene analysis. RESULTS: A statistically significant decrease in LAL activity was found in patients diagnosed with CC compared to the healthy group. LIPA gene analysis did not detect CESD in any patient group. Correlation analysis showed a positive correlation between LAL activity and white blood cell and platelet counts in both healthy volunteers and CC patient groups. In the univariate and multivariate logistic regression analysis of the parameters associated with the MELD of ≥10 in patients with CC, significant relationship was found between the MELD of ≥10 and the LAL activity. DISCUSSION: In our study, LAL activity was significantly lower in CC patients than in the normal population. LAL activity level appears to be a parameter that can be used to assess the severity of cirrhosis.

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.

Unexpected Diagnosis in an Adolescent With Bruises and Ecchymosis: Celiac Disease.

ABSTRACT: Acquired coagulopathy is a rare but challenging diagnosis for pediatric emergency physicians. Although the coagulopathy usually presents with mild skin and mucosal hemorrhages, it also can lead to life-threatening events. Thus, accurate interpretation of hints obtained from a detailed history, physical examination, and laboratory findings is essential for the prompt diagnosis and management. This case demonstrates an uncommon cause of coagulopathy; celiac disease that presented with spontaneous bruises and ecchymosis in an adolescent.

Inflammatory rheumatic diseases in patients with ochronotic arthropathy.

BACKGROUND: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients. METHODS: Adult AKU patients with symptoms suggestive of OcA were included. Patients underwent a detailed rheumatological assessment. Laboratory testing, including autoantibodies and radiological investigations such as conventional X-rays, and magnetic resonance imaging (MRI) were performed. RESULTS: Eight out of 12 (66%) patients had symptoms consistent with OcA. The median age at OcA symptoms was 36 (27-48) years, and the presenting symptom was back pain in 87.5% of the patients. All patients had chronic back pain, and three (37.5%) had an inflammatory type of pain character. Radiographic sacroiliitis based on X-rays was present in 2 (25%) cases. MRI of the sacroiliac joints documented bone marrow edema in five (62.5%), and spinal MRI identified corner inflammatory lesions in three patients (37.5%). One patient (12.5%) had rheumatoid arthritis. Extra-articular involvement, including enthesitis (n = 1; 12.5%), interstitial lung disease (n = 1; 12.5%), and scleritis (n = 1; 12.5%), was also noted. CONCLUSION: The frequent occurrence of OcA-related inflammatory manifestations in our patients contradicts the conventional concept of OcA as a non-inflammatory disorder. The activation of inflammatory pathways, possibly by the HGA products, may responsible for this condition.Significance and innovationsAbout three-fourths of adult ochronotic arthropathy (OcA) patients in our group had associated inflammatory disease.OcA associated inflammatory diseases were showing a severe phenotypeNearly half of the OcA patients required early prosthesis operations compared to their healthy counterparts.

ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy.

Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy are a spectrum of rare lysosomal storage disorders characterized by acid ceramidase deficiency (ACD), resulting from pathogenic variants in N-acylsphingosine amidohydrolase 1 (ASAH1). Other than simple listings provided in literature reviews, a curated, comprehensive list of ASAH1 mutations associated with ACD clinical phenotypes has not yet been published. This publication includes mutations in ASAH1 collected through the Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease (NHS), ClinicalTrials.gov identifier NCT03233841, in combination with an up-to-date curated list of published mutations. The NHS is the first to collect retrospective and prospective data on living and deceased patients with ACD presenting as Farber disease, who had or had not undergone hematopoietic stem cell transplantation. Forty-five patients representing the known clinical spectrum of Farber disease (living patients aged 1-28 years) were enrolled. The curation of known ASAH1 pathogenic variants using a single reference transcript includes 10 previously unpublished from the NHS and 63 that were previously reported. The publication of ASAH1 variants will be greatly beneficial to patients undergoing genetic testing in the future by providing a significantly expanded reference list of disease-causing variants.

Analysis of hematological parameters in patients treated with ketogenic diet due to drug-resistant epilepsy.

Benefits of the ketogenic diet (KD) in epileptic patients are well known while less is known about the nutritional risks of the diet and its potential impacts on biochemical nutritional status. In this study, we aimed to evaluate the hematological parameters of patients who have drug-resistant epilepsy and are treated with KD. Fifty-three patients with drug-resistant epilepsy (mean age 7.4 ± 4.4 years [2-18], 23 [43.4%] female) were included in the study. Demographic and laboratory data of the patients were retrospectively analyzed at baseline and Month 6 and Month 12 of the treatment. Repeated measures ANOVA (post hoc Bonferroni correction) and Friedman test were used to assess the changes in data during the treatment. Mean hemoglobin levels increased by 0.594 g/dL after 6 months (p = 0.001) and by 0.602 g/dL after 12 months of the treatment (p = 0.002). Mean hematocrit level was found to be significantly increased at Month 6 and 12 of the treatment compared to baseline [F(2,94) = 8.9, p < 0.0001]. An increase in MCV levels was determined with the KD treatment [F(2,94) = 19.7, p < 0.0001]. Mean level of vitamin B12 was found to be significantly increased in Month 12 of treatments compared to Month 6 [F(1.686,72.479) = 3.472, p = 0.035]. There was no significant effect of KD on other hematological parameters (red blood cell, white blood cell and platelet counts, serum iron, total iron-binding capacity, transferrin saturation, and ferritin and folic acid levels). We can conclude that KD increases levels of hemoglobin, hematocrit, MCV, and serum vitamin B12 in patients with intractable epilepsy. Prospective, multi-center, longitudinal studies are needed to confirm our results.

The Effects of Breastfeeding in Infants With Phenylketonuria.

PURPOSE: In the early years of phenylketonuria (PKU) treatment, mothers and healthcare professionals often decide to discontinue breastfeeding after the diagnosis of PKU in infants. It was believed to be the only effective way to monitor the infant's intake and allow for precise titration and measurement of the intake of phenylalanine (Phe). In the early 1980s, with the determination of low concentration of Phe in breast milk, breast milk supplemented with Phe-free formula has become an acceptable dietary treatment for infants with PKU. Today, breastfeeding is encouraged and well established in PKU patients. The aim of the present study is to investigate the prevalence and duration of breastfeeding, the effect of breastfeeding on serum Phe levels, and weight gain in infants with PKU. DESIGN AND METHODS: Data were collected from chart reviews. Medical records of 142 children with PKU diagnosed via the national neonatal screening program were analyzed retrospectively. RESULTS: Of the 41 infants with complete medical records, 40 (97.6%) were breastfed following delivery whereas only one (2.4%) was bottle fed. After the diagnosis, breastfeeding was continued in 25 (61%) infants with phenylalanine-free amino acid based protein substitute. The mean duration of breastfeeding was 7.4±4.0 (1-15) months. Serum Phe concentration of breastfed infants (280±163 µmol/L) was significantly lower than non-breastfed infants (490±199 µmol/L) (p<0.001). Mean monthly weight gain in the first year of life was significantly higher in breastfed patients (493±159 g/month) compared to non-breastfed patients (399±116 g/month) (p=0.046). CONCLUSION: In the first year of life, weight gain and serum Phe levels were more favorable in breastfed infants with PKU compared to non-breastfed infants with PKU.

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy.

Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1α, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments.

Perilipin polymorphisms are risk factors for the development of obesity in adolescents? A case-control study.

BACKGROUND: The variations in perilipin gene (PLIN) were previously associated with obesity. We examined the association of polymorphisms at the PLIN locus in adolescents with obesity and their connection with serum adipokines. METHODS: A total of 308 children (206 obese, 66.8% and 102 healthy control, 33.2%) between the ages of 10-18 years were included into the study. PLIN gene analysis [PLIN 1, PLIN 4, PLIN 6, PLIN 5'UTR-1234 C > G and PLIN 10171 A/T] were studied by Real Time-PCR. Serum leptin, adiponectin, resistin and ghrelin levels were studied by ELISA method in both groups and their link with perilipin polymorphisms were analyzed. RESULTS: Serum leptin level was found significantly high in obese adolescents. Other adipokine levels were similar in both groups. The incidence of PLIN 1, PLIN 4, PLIN 5'UTR-1234 C > G and PLIN 10171 A/T minor and major alleles was similar in both groups. PLIN 6 T/T allele was determined significantly high in obese adolescents compared to that of control group. No correlation was detected between perilipin polymorphism and serum levels of adipokines. CONCLUSION: The PLIN 6 polymorphism of the perilipin gene may influence the risk of the obesity during adolescence. TRIAL REGISTRATION: Retrospectively registered.

Aminotransferase elevations in rotavirus positive and negative acute gastroenteritis and its relation with disease severity.

BACKGROUND: The aim of this study was to investigate the frequency of elevated alanine (ALT) and aspartate aminotransferase (AST) levels in children with rotavirus positive and negative gastroenteritis as well as the average time to normalization of liver enzymes. METHODS: Into the study 298 patients with rotavirus positive and 321 patients with rotavirus negative gastroenteritis were enrolled. RESULTS: Mean AST (56.9±2.1 and 40.2±0.9 U/L, respectively, P=0.000) and ALT (33.1±1.7 and 22.4±0.8 U/L, respectively, P=0.000) levels were significantly higher in the rotavirus positive than rotavirus negative patients. Logistic regression analysis showed that rotavirus positivity was significant independent factor for both AST and ALT elevation. Severity of gastroenteritis was another significant independent factor for ALT elevation. The average transaminase normalization time for AST and ALT levels were similar both rotavirus positive and negative groups. CONCLUSIONS: Rotavirus positivity and severity of gastroenteritis were independent risk factors for elevated ALT levels in children with gastroenteritis.

A novel mutation in the glycine decarboxylase gene in patient with non-ketotic hyperglycinemia.

Non-ketotic hyperglycinemia (NKH) is a rare inborn error of metabolism and is caused by a glycine cleavage system deficiency. Eighty-five percent of patients present with the neonatal type of NKH, the infants initially develop lethargy, seizures, and episodes of apnea, and most often death. Between 60-90% of cases are caused by mutations in the glycine decarboxylase (GLDC). We believed that more mutation reports especially for rare disease as NKH help to evaluate the genotype-phenotype relationship in patients with GLDC. In this study, we describe a case of a neonate admitted to intensive care unit with hypotonia, respiratory failure, lethargy, poor feeding. Due to the history of 2 non-ketotic hyperglycinemia diagnosed male siblings, molecular prenatal diagnosis in patient was performed and a novel c.2963G>A (Arg998Gln) homozygous mutation within the GLDC gene has been detected. We aimed to contribute to mutation knowledge pool of GLDC gene with a novel mutation.

The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients.

BACKGROUND: Previous studies investigating the known risk factors of atherosclerosis in phenylketonuria patients have shown conflicting results. The primary aim of our study was to investigate the serum atherogenic markers in adolescent classical phenylketonuria patients and compare these parameters with healthy peers. The secondary aim was to compare these atherogenic markers in well-controlled and poorly controlled patients. METHODS: A total of 59 patients (median age: 12.6 years, range: 11-17 years) and 44 healthy controls (median age: 12.0 years, range: 11-15 years) were enrolled in our study. Phenylketonuria patients were divided into two groups: well-controlled (serum phenylalanine levels below 360 µmol/L; 24 patients) and poorly controlled patients (serum phenylalanine levels higher than 360 µmol/L). RESULTS: The mean high-density lipoprotein cholesterol levels of well-controlled patients (1.0±0.2 mmol/L) were significantly lower compared with poorly controlled patients and controls (1.1±0.2 mmol/L, p=0.011 and 1.4±0.2 mmol/L, p<0.001, respectively). Poorly controlled patients had lower high-density lipoprotein cholesterol levels than healthy controls (p=0.003). Homocysteine levels of both well-controlled (9.8±6.4 µmol/L) and poorly controlled (9.2±5.6 µmol/L) patients were higher compared with controls (5.8±1.8 µmol/L, p<0.01). The mean platelet volume of well-controlled patients (9.5±1.1 fL) was higher than that of poorly controlled patients and controls (8.9±0.8 fL, p=0.024 and 7.7±0.6 fL, p<0.001, respectively). CONCLUSION: Lower high-density lipoprotein cholesterol and higher homocysteine and mean platelet volume levels were detected in phenylketonuria patients. In particular, these changes were more prominent in well-controlled patients. We conclude that phenylketonuria patients might be at risk for atherosclerosis, and therefore screening for atherosclerotic risk factors should be included in the phenylketonuria therapy and follow-up in addition to other parameters.

Fecal calprotectin: can be used to distinguish between bacterial and viral gastroenteritis in children?

OBJECTIVE: Fecal calprotectin is used as a good indicator of intestinal mucosal inflammation. The aim of this study is to evaluate the diagnostic value of fecal calprotectin (f-CP) for the etiology of acute gastroenteritis in children. MATERIALS AND METHODS: All patients presenting with acute diarrhea (<18 years) who had 3 or more soft or watery stools per day were enrolled in this study. Stool microscopic examination and cultures for bacteria and parasites were performed. Polymerase chain reaction test was also applied to stool samples for viruses (Rotavirus, Adenovirus, Norwalk, and Astrovirus). The level of f-CP was carried out by using enzyme-linked immunosorbent assay test. RESULTS: Eighty-four patients with diarrhea were enrolled. The f-CP level was higher in patients with microscopic examination positive (n=17) (median with interquartile range, 1610.0 [908.8-2100] mg/L) than in patients with microscopic examination negative (n=67) (123.8 [25.0-406.3] mg/L) (P<.001). Concentrations of f-CP in patients with stool culture positive (1870.0 [822.5-2100] mg/L) were significantly elevated compared with the concentrations of the patient with virus detected in stool (95.0 [21.3-240.9] mg/L) (P<.001). In the diagnosis for bacterial acute gastroenteritis, the area under the receiver operating characteristic curve for f-CP was 0.867 (95% confidence interval, 0.763-0.971), sensitivity was 88.9%, and specificity was 76.0% if the threshold was taken as 710 mg/L. CONCLUSION: We conclude that f-CP, which is useful, valuable, noninvasive, easily and rapidly measured laboratory test along with simple microscopic examination of stool, can be used as an indicator of intestinal inflammation and to distinguish the bacterial gastroenteritis from the viral gastroenteritis.