First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

New molecular insights into the A218V variant impact on the steroidogenic acute regulatory protein (STAR) associated with 46, XY disorders of sexual development.

Disorders of sexual development (DSD) are an abnormal congenital conditions associated with atypical development of the urogenital tract and external genital structures. The steroidogenic acute regulatory (STAR) gene, associated with congenital lipoid adrenal hyperplasia (CLAH), is included in the targeted gene panel for the DSD diagnosis. Therefore, the genetic alterations of the STAR gene and their molecular effect were examined in the CLAH patients affected with DSD. Ten different Iranian families including twelve male pseudo-hermaphroditism patients with CLAH phenotype were studied using genetic linkage screening and STAR gene sequencing in the linked families to the STAR locus. Furthermore, the structural, dynamical, and functional impacts of the variants on the STAR in silico were analyzed. Sanger sequencing showed the pathogenic variant p.A218V in STAR gene, as the first report in Iranian population. Moreover, modeling and simulation analysis were performed using tools such as radius of gyration, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and molecular docking showed that p.A218V variant affects the residues interaction in cholesterol-binding site and the proper folding of STAR through increasing H-bound and the amount of α-Helix, deceasing total flexibility and changing fluctuations in some residues, resulting in reduced steroidogenic activity of the STAR protein. The study characterized the structural and functional changes of STAR caused by pathogenic variant p.A218V. It leads to limited cholesterol-binding activity of STAR, ultimately leading to the CLAH disease. Molecular dynamics simulation of STAR variants could help explain different clinical manifestations of CLAH disease.

Molecular characterization of a large cohort of mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis study (IMPRESsion).

Mucopolysaccharidoses (MPSs) are rare, heterogeneous inborn errors of metabolism (IEM) diagnosed through a combination of clinical, biochemical, and genetic investigations. The aim of this study was molecular characterization of the largest cohort of Iranian MPS patients (302 patients from 289 unrelated families), along with tracking their ethnicity and geographical origins. 185/289 patients were studied using an IEM-targeted NGS panel followed by complementary Sanger sequencing, which led to the diagnosis of 154 MPS patients and 5 non-MPS IEMs (diagnostic yield: 85.9%). Furthermore, 106/289 patients who were referred with positive findings went through reanalysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, 90 harbored novel variants, and 9 had copy number variations. MPS IV was the most common type (34.8%) followed by MPS I (22.7%) and MPS VI (22.5%). Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962T>C [p.Leu321Pro], c.281C>A [p.Ser94*]), GALNS (c.319G>A [p.Ala107Thr], c.860C>T [p.Ser287Leu], c.1042A>G [p.Thr348Ala]), and IDUA (c.1A>C [p.Met1Leu], c.1598C>G [p.Pro533Arg], c.1562_1563insC [p.Gly522Argfs*50]). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants.

Cognitive function in untreated subjects with mild hyperphenylalaninemia: a systematic review.

BACKGROUND: This systematic review study aims to evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) without treatment. METHODS: A systematic literature search was done from the 1st of May to the 30th of July in 2021 on published studies. The search strategy was ((hyperphenylalaninemia) OR (phenylketonuria) AND (cognition)). We use PubMed, Scopus, and the Web of Science databases. Studies which reported their findings regarding the cognitive function of patients with mHPA (screening serum phenylalanine > 120 and < 600 µmol/L) were included and reviewed. RESULTS: From initially retrieved 2805 studies, finally, 15 studies (10 on untreated patients with Phe levels below 360 µmol/L, 7 on untreated patients with Phe levels between 360 and 600 µmol/L, four 120-600 µmol/L) were selected. Most of the studies used the Wechsler Intelligence Scale for IQ evaluation, two (2/15) of them used the Stanford-Binet test and two used both tests. Four studies have reported a worse cognitive outcome compared to the control group, and in one study, relative defects in attention and working memory were reported. Other studies have reported normal IQ levels and no significant cognitive defects. CONCLUSION: It is suggested that Phe levels between 120 and 360 µmol/L are generally safe. Some studies showed that untreated patients with higher levels might show some degrees of cognitive impairment. In conclusion, current knowledge is insufficient to state that treatment is not required for HPA patients to preserve their cognitive status, especially in patients with Phe levels of 360-600 µmol/L. Further studies with a larger sample size and standardized cognitive function evaluation tools are needed.

Prevalence of nephrocalcinosis in children with congenital adrenal hyperplasia.

Background: We aimed to investigate the prevalence of nephrocalcinosis (NC) among children with diagnosed congenital adrenal hyperplasia (CAH). Our findings would be helpful for earlier diagnosis, management, and prevention of NC-related complications. Materials and Methods: In this cross-sectional study, children with CAH, aged <18 years old who were regularly referred for follow-up, were included. The information of the patients was extracted from their medical files, and they underwent renal ultrasonography for evaluation of the presence of NC. Results: From 120 studied patients with CAH, four patients (3.3%) had NC. The prevalence of NC was higher in males than females (P = 0.05). Mean age and age of CAH diagnosis had a trend to be lower in CAH patients with NC than those without. Regression analysis indicated significant association between NC and sex (P = 0.027, r = 2.24). Conclusion: The results of this study indicated a 3.3% prevalence rate of NC for children with CAH. NC had a trend to be more prevalent in male children with CAH. Though it was not significantly different but given that the mean age and age at diagnosis of CAH in children with CAH and NC was lower that CAH patients without NC, it is suggested that in patients with CAH and NC other factors such as genetic background or unknown disease related factors are associated with hypercalcemia and NC.

The effects of whole grain intake on anthropometric measures in overweight and obese children: a crossover randomised clinical trial.

Whole-grain foods have been reported to affect body weight and satiety. However, we are aware of no study in this regard among children. The present study aimed to determine the effects of whole grain consumption on anthropometric measures in overweight or obese children. In this randomised crossover clinical trial, forty-four overweight or obese girls participated. After a 2-week run-in period, subjects were randomly assigned to either intervention (n 44) or non-intervention (n 44) groups. Subjects in the intervention group were given a list of whole-grain foods and were asked to obtain half of their grain servings from these foods each day for 6 weeks. Individuals in the non-intervention group were asked not to consume any of these foods. A 4-week washout period was applied. Then, participants were crossed over to the alternate arm. The measurements were done before and after each phase. Mean age, weight and BMI of participants were 11·2 (sd 1·49) years, 51·2 (sd 10·2) kg and 23·5 (sd 2·5) kg/m2, respectively. Despite the slight reduction in weight and BMI, there were no significant differences in changes in these anthropometric measures. We found a significant effect of whole grain intake on waist circumference (-2·7 v. 0·3 cm, P = 0·04). No significant changes in hip circumference were observed. Changes in the prevalence of overweight, obesity and abdominal obesity were not significantly different. This study indicated a beneficial effect of whole-grain foods on waist circumference in overweight children; however, these foods did not influence weight and BMI.

A rare enzymatic defect, true isolated 17,20-lyase deficiency leading to endocrine disorders and infertility: case report.

The cytochrome P450 17A1 catalyzes the formation of 17-hydroxysteroids and 17-ketosteroid. Most defects in CYP17A1 impair both enzymatic activities and cause a combined 17α-hydroxylase/17,20-lyase deficiency, which impairs hormone production (cortisol and sex steroids), sexual development, and puberty. Isolated 17,20-lyase deficiency is usually defined by evidently normal activity of 17α-hydroxylase with a dramatic decline of 17,20-lyase activity or complete inactivity. The changes in enzyme activity lead to a lack in the production of sex steroids with normal levels of glucocorticoid and mineralocorticoid hormones. A 24-years-old married woman, as a product of a consanguineous marriage, presented with infertility and a background marked by primary amenorrhea. Laboratory data showed low normal serum cortisol levels and low levels of 17-hydroxyprogesterone. Also, her adrenal androgens were low but estradiol was normal. The chromosomal investigation uncovered a male karyotype of 46, XY. These clinical and laboratory evidence confirm the determination of an isolated 17,20-lyase deficiency in a genotypic male.

Effect of fermented camel milk on glucose metabolism, insulin resistance, and inflammatory biomarkers of adolescents with metabolic syndrome: A double-blind, randomized, crossover trial.

BACKGROUND: This study, for the first time, aimed to assess the effects of fermented camel milk (FCM) on glycemic and inflammatory parameters related to metabolic syndrome (MetS), an aggregation of cardiometabolic risk factors, in adolescents. MATERIALS AND METHODS: In a double-blind, randomized crossover trial, overweight/obese adolescents (fulfilling MetS criteria, aged 11-18 years) were randomly assigned to receive FCM 250 cc per day for an 8-week period, a 4-week washout, and then diluted cow's yogurt (DCY) 250 cc/day for another 8-week period, or the reverse sequence. Fasting blood sugar (FBS), fasting insulin, insulin resistance by three equations, incretin hormone glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP1) as well as inflammatory markers such as interleukin 6 (IL6) and tumor necrosis factor-alpha (TNF-α) were measured before and after each of the four periods. A 3-day food record and physical activity questionnaire were completed before each period. Statistical analyses were done using Minitab and SPSS software considering the significance level of 0.05. RESULTS: Twenty-four participants with a mean (standard deviation) age of 13.77 (1.87) years (range: 10.45-16.25 years) (58% girls) completed the study. It resulted in nonsignificant mean reduction in IL6 (-18.28 pg/mL [95% confidence interval [CI]: -47.48; 10.90]; P = 0.20) and nonsignificant increase in glucose metabolizing hormones such as GIP (683.10 pg/mL [95% CI: -457.84; 1824.0]; P = 0.22) and GLP1 (6.98 pg/mL [95% CI: -66.61; 80.57]; P = 0.84) by FCM consumption in comparison to DCY. Nonsignificant decrease was observed in TNF-α in the first periods of the study. The changes of FBS, fasting insulin, and insulin resistance indices were not statistically significant as well. CONCLUSION: According to preliminary positive influences of FCM on inflammatory markers, and findings related to glucose metabolism, we suggest conducting further studies on its clinical impacts.

Lipid regulatory genes polymorphism in children with and without obesity and cardiometabolic risk factors: The CASPIAN-III study.

BACKGROUND: Genetically, predisposed children are considered as at-risk individuals for cardiovascular disease. In this study, we aimed to compare the frequency of four-lipid regulatory polymorphism in obese and normal-weight children with and without cardiometabolic risk factors. MATERIALS AND METHODS: In this nested case-control study, 600 samples of four groups of participants consisted of those with normal weight with and without cardiometabolic risk factors and obese with and without cardiometabolic risk factors. Allelic and genotypic frequencies of GCKR (rs780094), GCKR (rs1260333), MLXIPL (rs3812316), and FADS (rs174547) polymorphisms were compared in the four studied groups. RESULTS: Data of 528 samples were complete and included in this study. The mean (standard deviation) age of participants was 15.01 (2.21) years. Frequency of tt allele (minor allele) of GCKR (rs1260333) polymorphism was significantly lower in normal weight metabolically healthy participants than metabolically unhealthy normal weight (MUHNW) and obese children with and without cardiometabolic risk factor (P = 0.01). Frequency of ga allele of GCKR (rs780094) polymorphism was significantly higher in normal weight children with cardiometabolic risk factor than in their obese counterparts with cardiometabolic risk factor (P = 0.04). Frequency of cg and gg alleles (minor type) of MLXIPL (rs3812316) polymorphism in normal weight metabolically healthy participants was significantly higher than MUHNW (P = 0.04) and metabolically healthy obese children (P = 0.04). CONCLUSION: The findings of our study indicated that the minor allele of GCKR (rs1260333) single nucleotide polymorphisms (SNPs) could have pathogenic effect for obesity and cardiometabolic risk factors. Ga allele of GCKR (rs780094) SNPs had a protective effect on obesity. Minor alleles of MLXIPL (rs3812316) could have a protective effect for obesity and cardiometabolic risk factors.

Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents.

OBJECTIVES: This study aims to evaluate the effects of some probiotics on sonographic and biochemical nonalcoholic fatty liver disease (NAFLD). METHODS: This randomized triple-blind trial was conducted among 64 obese children with sonographic NAFLD. They were randomly allocated to receive probiotic capsule (containing Lactobacillus acidophilus ATCC B3208, 3 × 10 colony forming units [CFU]; Bifidobacterium lactis DSMZ 32269, 6 × 10 CFU; Bifidobacterium bifidum ATCC SD6576, 2 × 10 CFU; Lactobacillus rhamnosus DSMZ 21690, 2 × 10 CFU) or placebo for 12 weeks. RESULTS: After intervention, in the probiotic group the mean levels of alanine aminotransferase decreased from 32.8 (19.6) to 23.1 (9.9) U/L (P = 0.02) and mean aspartate aminotransferase decreased from 32.2 (15.7) to 24.3 (7.7) U/L (P = 0.02). Likewise the mean cholesterol, low-density lipoprotein-C, and triglycerides as well as waist circumference decreased in the intervention group, without significant change in weight, body mass index, and body mass index z score. After the trial, normal liver sonography was reported in 17 (53.1%) and 5 (16.5%) of patients in the intervention and placebo groups, respectively. CONCLUSIONS: The present findings suggest that a course of the abovementioned probiotic compound can be effective in improving pediatric NAFLD.

Effect of long-term Vitamin C intake on vascular endothelial function in diabetic children and adolescents: A pilot study.

BACKGROUND: This study attempted to determine the effects of long-term use of Vitamin C on vascular endothelial function. MATERIALS AND METHODS: During a pilot clinical trial study conducted at Imam Hussein Hospital (Isfahan) in 2014-2015, a total of forty diabetic patients were selected and then assigned randomly into two twenty-subject groups receiving Vitamin C and placebo tablets. The patients were treated with Vitamin C or placebo for 6 months. All patients were examined through echocardiography in terms of cardiac function before and after treatment. To evaluate the endothelial function (flow-mediated dilatation [FMD], intima-media thickness), they underwent arterial Doppler. Moreover, the chemical indices of vascular function were tested through intercellular adhesion molecule and vascular cell adhesion molecule (VCAM). Finally, the results were compared between the two groups. RESULTS: Based on the results, the mean left ventricular mass significantly reduced after the intervention in the group treated with Vitamin C (from 76.35 ± 25.6-68.62 ± 22.66; P = 0.015) while there was no significant difference observed in the control group (from 67.58 ± 25.38-71.63 ± 26.84; P = 0.19) but no statistically difference between the two groups-based repeated measures ANOVA test (P = 0.6). In addition, the mean of VCAM changes was significantly difference between the two groups (P < 0.001). CONCLUSION: Long-term use of Vitamin C in diabetic patients can improve certain echocardiographic parameters such as ejection fraction, fractional shortening, and FMD, which in turn enhances vascular endothelial function.

The effect of Citrus Aurantifolia (Lemon) peels on cardiometabolic risk factors and markers of endothelial function in adolescents with excess weight: A triple-masked randomized controlled trial.

Background: Childhood obesity is becoming a global problem and its incidence is increasing. The role of dietary intervention with fruits containing vitamin C and flavonoid to control obesity consequences in childhood has not been yet defined. Lemon (Citrus aurantifolia) peels contain flavonoid, pectin and vitamin C. We aimed to compare the effects of lemon peels and placebo on cardiometabolic risk factors and markers of endothelial function among adolescents with overweight and obesity. Methods: In this triple-masked, randomized controlled trial, 60 overweight/obese adolescents were enrolled in a 4-week trial. Eligible participants were randomly assigned into two groups of equal number receiving daily oral capsules containing lemon powder or placebo. Fasting blood sugar, lipid profile, ICAM-1 and VCAM-1, as well as systolic and diastolic blood pressure were compared between the two groups before and after administration of medication and placebo. Results: Of the total 60 enrolled patients, 30 and 29 patients in the lemon and control groups completed the study, respectively. The results of within-group analysis demonstrated a slight reduction in body mass index, LDL-C and systolic blood pressure in the lemon group, but no between group differences existed in the studied variables. Conclusion: This study revealed that consumption of lemon peel extract has some beneficial effects for childhood obesity; however, no considerable effect was documented on anthropometric measures and biochemical factors. Future studies with longer follow up are highly recommended.

Effect of the peels of two Citrus fruits on endothelium function in adolescents with excess weight: A triple-masked randomized trial.

BACKGROUND: Obesity induces endothelial dysfunction even in the pediatric age group. The possible protective effects of fruits and herbal products on the endothelial dysfunction of obese children remain to be determined. This study aims to investigate the effects of lemon and sour orange peels on endothelial function of adolescents with excess weight. MATERIALS AND METHODS: This triple-masked, randomized placebo-controlled trial was conducted for 1-month among 90 overweight and obese participants, aged 6-18 years. They were randomly assigned into three groups of equal number receiving daily oral capsules containing lemon or sour orange powder or placebo. Flow-mediated dilatation (FMD) was compared between three groups by using analysis of covariance. RESULTS: Overall, 30 participants in the lemon group, 27 in the sour orange group and 29 in the control group completed the trial. After the trial, mean FMD was significantly (P < 0.001) higher in the lemon group (11.99 ± 4.05) and in the sour orange group (12.79 ± 5.47) than in the placebo group (6.45 ± 2.79). FMD percent change was 145.02 ± 24.34 in the lemon group, 142.04 ± 16.11 in the sour orange group, and 46.73 ± 5.16 in controls (P < 0.001). CONCLUSION: This trial showed that consumption of extracts of lemon and sour orange peels, which contain plenty amounts of antioxidants, flavonoids, pectin, and vitamin C, might have significant benefits on endothelial function in children and adolescents with excess weight. Trial registry code: IRCT201311201434N10.

The Dietary Approaches to Stop Hypertension (DASH) diet affects inflammation in childhood metabolic syndrome: a randomized cross-over clinical trial.

BACKGROUND: The effects of the DASH (Dietary Approaches to Stop Hypertension) diet on inflammation in childhood metabolic syndrome (MetS) have still to be identified. OBJECTIVE: To examine the effects of the DASH diet on markers of systemic inflammation in adolescents with MetS. METHODS: In this randomized, cross-over clinical trial, 60 postpubescent girls with MetS were randomly assigned to receive either the DASH diet menu cycles or usual dietary advice (UDA) for 6 weeks. After a 4-week washout period, participants were crossed over to the alternate arm. The DASH diet was designed to maintain the current body weight. This diet contained high amounts of fruit, vegetables and low-fat dairy products and was low in saturated fats and cholesterol. UDA consisted of general oral advice and written information about healthy food choices based on the Healthy Eating Plate. Compliance to the DASH diet was assessed through quantification of plasma vitamin C levels. Fasting venous blood samples were taken 4 times from each participant: at baseline and at the end of each study arm. Circulating levels of biomarkers of systemic inflammation were quantified according to standard protocols. RESULTS: Mean (SD) age and weight of participants was 14.2 years (1.7) and 69 kg (14.5), respectively. Serum vitamin C levels tended to increase during the DASH phase compared with the UDA phase (16.8 ± 12.9 vs. -13.8 ± 9.7 ng/dl, respectively, p = 0.06) indicating a relatively good compliance to the DASH diet. Adherence to the DASH diet, compared to the UDA, had a significant effect on serum high-sensitivity C-reactive protein levels (p = 0.002). This effect remained significant even after adjustment for weight changes and after further controlling for changes in lipid profiles. We did not observe any significant effect of intervention on levels of serum tumor necrosis factor-alpha, interleukin (IL)-2, IL-6 and adiponectin, in either the crude or adjusted models. There were no significant group*time interactions for any dependent variable, except for IL-6; this was close to the significant level. CONCLUSION: In summary, consumption of the DASH eating pattern for 6 weeks may reduce circulating levels of hs-CRP among adolescents with MetS. Other inflammatory markers were not affected by the DASH diet.

Visual Perception in Children with a History of Hypoglycemia due to Hyperinsulinism.

Objectives: Hyperinsulinism refers to improper insulin secretion in the presence of low plasma glucose, causing severe and persistent hypoglycemia in infants and children. The brain's occipital lobe, which includes the visual and plays an essential role in visual perception is specifically sensitive to hypoglycemia-induced damage. The present study aims to investigate the visual perception in children suffering from hyperinsulinism and to compare it with the control group. Materials & Methods: This cross-sectional control study, conducted in 2020 in Isfahan, Iran, involved 20 children aged 4-13 years with hyperinsulinism and 20 healthy children of the same age and gender for comparison. In both groups, the measuring instrument was the Test of Visual Perceptual Skills (non-motor) Third Edition. Results: The mean visual perceptual quotient in the case and control groups was 80.50±26.74 and 116.50±7.56 (p-value<0.001), respectively. The results overall indicated that children suffering from hyperinsulinism were weaker than healthy children in all areas of visual perception. Conclusion: Based on the obtained results, it is recommended that children suffering from hyperinsulinism be screened regarding visual perceptual disorders since this screening may be helpful in initiating different rehabilitation programs among these patients.

Association between maternal and cord blood thyroid hormones, and urine iodine concentration with fetal growth.

OBJECTIVES: We planned to evaluate the association of fetal and maternal thyroid hormones and maternal iodine status with neonates' anthropometric parameters. METHODS: In this cross-sectional study, levels of thyrotropin were measured in maternal serum in the first trimester of pregnancy, and thyrotropin (TSH) and free thyroxin (fT4) were measured in cord blood serum samples at birth. Urinary iodine concentration (UIC) levels in random urine samples of mothers were measured in the third trimester of pregnancy. The relationship between UIC and thyroid hormone levels of mothers with neonates' anthropometric birth parameters of neonates was evaluated. RESULTS: One hundred eighty-eight mother-newborn pairs completed the study. Mean (SD) of cord blood TSH (CB-TSH), cord blood-free thyroxin (CB-FT4) values, and maternal TSH (M-TSH) levels were 8.8 (7.3) mIU/L, 1.01 (0.2) ng/dL, and 2.2 (0.9) mIU/L, respectively. After adjusting for confounders, there was a positive significant association between female neonate length and maternal TSH and log log-transformed CB TSH (LN_CB-TSH) (p<0.05). Median UIC (Q1-Q3) was 157 (53-241) µg/L, and there was no association between birth weight, birth length, and head circumferences of neonates and mothers' UIC (p>0.05). CONCLUSIONS: We found a positive correlation between maternal TSH in the first trimester of pregnancy and the birth length of newborns, and a negative correlation was observed between CB-TSH and birth length in girls, but it did not provide conclusive evidence for the relationship between maternal and neonatal thyroid hormone levels and birth weight. There was no association between maternal UIC levels in the third trimester and birth anthropometric parameters.

Quality of Life in Patients with Phenylketonuria: A Systematic Review.

The impact of phenylketonuria (PKU) on Quality of life (QoL) has been a topic of interest in recent research. This article reviews current researches on the impact of PKU on QoL. The review examines factors that may influence QoL, such as age, metabolic control, and treatment adherence. In this systematic review study, relevant articles were identified using a search strategy built with the keywords phenylketonuria, PKU, or hyperphenylalaninemia (or their synonyms) and QoL in Web of Science, Scopus, and PubMed databases. After identifying the articles, duplicates, reviews, scientific abstracts, articles published in languages other than English, and non relevant studies were excluded. The search strategy identified 951 records from databases, and after excluding duplicates, irrelevant studies, and those published in non English languages, 26 records were left that contained data on 1816 patients with PKU/hyperphenylalaninemia. The studies included both children/adolescents and adults. Overall, the studies found that the QoL of PKU patients was comparable to normative data, but some aspects such as emotional health and school functioning were lower. Metabolic control was found to significantly correlate with QoL. Younger patients and men had better QoL in several studies, while late treated patients and those with lower education had worse outcomes. It is concluded that QOL in patients with PKU is similar to the general population. However, given the chronic nature of the condition, it is important to pay special attention to their QoL. Poor QOL is associated with female gender, lower education, older age, and poor metabolic control.

Final height in children and adolescents with type 1 diabetes mellitus: A systematic review and meta-analysis.

PURPOSE: Considering the high prevalence of type 1 diabetes mellitus (T1DM) together with the importance of improved physical growth and the significance of promoting healthcare quality among T1DM children, this meta-analysis aims to determine mean final height in this population group. METHODS: We systematically searched PubMed, EMBASE, Web of Science, Scopus, and Cochrane databases for all studies published until May 2023 and reviewed references of published articles. Meta-analytic procedures were used to estimate the effect size (mean final height Z-score) among T1DM children in a random effects model. Significance values, weighted effect sizes, 95% CIs, and tests of homogeneity of variance were calculated. The included studies consisted of data from 3274 patients. RESULTS: The mean final height Z-score for T1DM children was -0.201 (n = 25 studies, 95% CI: -0.389, -0.013; I2 = 97%), -0.262 in males (n = 20 studies, 95% CI: -0.539, 0.015, I2 = 97.1%), and -0.218 in females (n = 18 studies, 95% CI: -0.436, 0, I2 = 94.2%). The non-significant negative association between age at diagnosis, HbA1c levels, and final height Z-score is suggested by the findings of the univariate meta-regression. CONCLUSION: Our findings indicated that children with T1DM have impaired linear growth and that monitoring of growth in these patient populations is an important issue in the management of T1DM. Due to a scarcity of studies providing data on the relationship between uncontrolled diabetes (increased HbA1c) and early diagnosis and final height, further investigation is warranted to determine whether there is indeed a correlation. Consequently, any conclusion regarding the association between uncontrolled diabetes (elevated HbA1c), early diagnosis of T1DM, and the increased risk of impaired linear growth or final height remains uncertain.

Validity and reliability of parent assessments of pubertal maturation among adolescent girls in Isfahan, Iran.

OBJECTIVES: The current paper presents the steps considered for validation of a questionnaire for assessment of sexual maturity among Iranian adolescent girls. METHODS: This cross-sectional study was performed in 2022 in Isfahan, Iran. Based on the Growth and Development Questionnaire that included both the Pubertal Development Scale (PDS) and Sexual Maturation Scale (SMS), two Persian questionnaires were prepared. The face validity, content validity, criterion validity, and reliability of the questionnaire were assessed. We compared agreement of two parent-reported measures of puberty, SMS and PDS, with clinical Tanner stages (TSs) as the gold standard. Percent agreement, Cohen's kappa coefficient, and Kendall's τ b were used to assess the agreement between maternal assessments with clinical TS. The intraclass correlation coefficient (ICC) and the Cronbach's α coefficient were also calculated to evaluate the reliability of the questionnaire. RESULTS: A total of 150 students aged 6-17 years with mean (SD) age of 10 (2.04) completed this study. The percentages of agreement for the mother-reported SMS in relation to clinical TS for breast stage and pubic hair stage were 60 % and 53.8 %, respectively. The percentages of agreement of the mother-reported PDS in relation to clinical TS for breast stage and pubic hair stage were 55.8 and 66 %, respectively. The weighted kappa coefficients showed moderate agreement, with weighted kappa ranging from 0.52 to 0.61. The mother-reported SMS and PDS showed high reliability. The Cronbach's alpha of the PDS and the SMS was 0.88 and 0.83, respectively. The ICC of the mother-reported SMS and the mother-reported PDS was 0.95 (0.92-0.98) and 0.97 (0.94-0.98), respectively. CONCLUSIONS: This study indicated that a maternal assessment of sexual maturity using the PDS or SMS can reliably estimate pubertal development in adolescent girls in an Iranian population.

Evaluation of cardiac findings in mucopolysaccharidosis.

PURPOSE: Mucopolysaccharidoses (MPS) are a group of rare genetic diseases and heart involvement is one of the important conflicts in most types, which may cause serious complications. We used M-Mode and two-dimensional speckle tracking echocardiography (2D-STE) to explore cardiovascular involvements in MPS patients. METHOD: The present cross-sectional study investigated the frequency of cardiac involvements in MPS patients. Included participants were MPS types I, II, III, IV, and VI who underwent specialized echocardiography exams to assess valvular function, systolic and diastolic function, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). RESULTS: 35 patients were enrolled in this study. The total mean age of patients was 9.58 ± 5.11 years and 71.4% were male. Type IV (40%) and type III (31.4%) were the most frequent MPS. Although LVEF did not differ notably among MPS types, GLS was significantly different (p = 0.029). Mitral regurgitation was observed remarkably more in MPS type III (p = 0.001) while mitral stenosis was more common in type III (p = 0.007). There was a significant association between LVEF and GLS (ß= -0.662; p = 0.025) and between LVEF and MPS type (ß = 1.82; p = 0.025) when adjusted for GLS. CONCLUSION: Cardiac complications are very common and are one of the most important causes of death in MPS patients. 2D-STE seems to be superior to M-Mode for detection of early and subclinical cardiac dysfunction in MPS patients.