Evaluation of the Efficacy and Safety of 3 Different Management Protocols in Pediatric Diabetic Ketoacidosis.

OBJECTIVE: Management protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among medical centers. The aim of this study was to investigate the efficacy and safety of 3 different fluid protocols in the management of DKA. METHODS: Fluid management protocols with sodium contents of 75, 100, and 154 mEq/L NaCl were compared. In all groups, after the initial rehydration, the protocols differed from each other in terms of the maintenance fluid, which had different rates of infusion and sodium contents. Clinical status and blood glucose levels were checked every hour during the first 12 hours. Biochemical tests were repeated at 2, 6, 12, 24, and 36 hours. RESULTS: The medical records of 144 patients were evaluated. Cerebral edema developed in 18% of the patients. The incidence of cerebral edema was lowest in the group that received fluid therapy with a sodium content of 154 mEq/L NaCl at least 4 to 6 hours and had a constant rate of infusion for 48 hours. The patients with cerebral edema had lower initial pH and HCO3 and severe dehydration with higher initial plasma osmolality. There was no significant difference between the groups in terms of the recovery times of blood glucose, pH, HCO3, and the time of transition to subcutaneous insulin therapy. CONCLUSIONS: Severity of acidosis and dehydration are associated with the development of cerebral edema. It can be concluded that fluid therapy with higher Na content and a constant maintenance rate may present less risk for the patient with DKA.

Determination of insulin resistance and its relationship with hyperandrogenemia,anti-Müllerian hormone, inhibin A, inhibin B, and insulin-like peptide-3 levels in adolescent girls with polycystic ovary syndrome

Background/aim: This study aims to investigate the association between polycystic ovary syndrome (PCOS) and obesity and insulin resistance (IR) with respect to anti-Müllerian hormone (AMH), inhibin A (INH-A), inhibin B (INH-B), and insulin-like peptide 3 (INSL3) levels, all factors which may have an impact on IR. Materials and methods: In this cross sectional study, 52 adolescent girls diagnosed with PCOS[groups:nonobese (NO), n = 23; overweight/obese (OW/O), n = 29] were included. Blood samples were obtained to measure AMH, INH-B, INH-A, and INSL3 levels, together with hormonal and biochemical assessments. Oral glucose tolerance test (OGTT) was performed and the indexes of IR [homeostasis model assessment: insulin resistance (HOMA-IR) and Matsuda index] were calculated. Results: Insulin resistance was 56.5% with OGTT and 30.4% with HOMA-IR in nonobese-PCOS girls. There was a correlation between INH-A and HOMA-IR even when controlled for body mass index (BMI). INH-B and FAI also had correlations with HOMA-IR which disappeared when controlled for BMI. In regression analyses, AMH (odds ratio = [0.903, P = 0.015) and FAI (odds ratio = 1.353, P = 0.023) are found to be contributors to IR. Their effect was BMI-independent. In ROC analysis, the cutoff value for FAI was 5.93 (sensitivity 71%) to define IR in PCOS girls. Conclusion: AMH and FAI may contribute to IR (defined by OGTT) in PCOS. FAI might be used as a supporting IR marker (defined by OGTT) in adolescent girls with PCOS.

Determinants of Increased Aortic Diameters in Young Normotensive Patients With Turner Syndrome Without Structural Heart Disease.

Factors associated with aortic dilation and dissection in patients with Turner syndrome (TS) remain unclear. We assessed magnetic resonance imaging-based aortic diameters at nine predefined anatomic positions and examined associations of increased aortic diameters with B-type natriuretic peptide (BNP), A-type NP (ANP), growth hormone treatment, insulin-like growth factor 1 (IGF1), and estrogen status. Forty-seven patients with TS aged 7.3-21 years and 34 healthy peers were enrolled in this study. Aortic diameters were higher in patients with TS at three positions than in controls (p < 0.05). History of GH treatment, pubertal status, and serum estradiol levels were not associated with increased aortic diameters. Patients with TS had higher plasma BNP and ANP levels than controls. BNP and IGF1 were independently associated with the increase in aortic diameters in TS at three positions of the ascending aorta (R2 = 0.361-0.458, p < 0.05 for all). At two positions of the descending aorta, only BNP emerged as an independent variable (R2 = 0.130-0.139, p < 0.05). We conclude that young, normotensive patients with TS had greater aortic diameters at several positions than healthy controls. BNP and IGF1 were independently associated with increased aortic diameters in TS.

The relationship between infancy growth rate and the onset of puberty in both genders.

BackgroundIn this study, we examined the hypothesis that weight gain and linear growth during the first years of life influence the onset of puberty both in girls and in boys.MethodsA cohort of 157 healthy children, aged 6-9 years, was evaluated and their growth patterns were analyzed retrospectively. Repeated measures mixed model was used to examine the longitudinal anthropometric data.ResultsGirls with pubertal signs were heavier than their peers starting at 9 months of age (P=0.02), and the difference became more evident over time (P<0.001). Accelerated weight gain between 6 and 15 months of age was found to increase the odds of having a pubertal sign at the study visit (odds ratio (OR)=34.5) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.004). Anthropometric indices of boys with or without pubertal signs were not significantly different at the study visit, but boys with accelerated height gain between 9 and 15 months of age were more likely to have pubertal signs (OR=15.8) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.016).ConclusionEarly growth acceleration might be important for the timing of puberty in both genders.

Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus.

Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12 ± 217.64 versus 270.02 ± 136.83 pg/mgCr; uHSP40/Cr 180.89 ± 118.59 versus 99.44 ± 62.49 pg/mgCr; uHSP60/Cr 114.40 ± 64.91 versus 70.50 ± 43.70 pg/mgCr; uHSP70/Cr 41.17 ± 28.42 versus 16.47 ± 7.32 pg/mgCr; uHSP90/Cr 175.64 ± 102.22 versus 107.61 ± 75.85 pg/mgCr) (p < 0.05). In 2013, uHSP70/Cr level increased significantly (51.08 ± 27.72 pg/mgCr; p = 0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p > 0.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59 pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children.

Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers.

OBJECTIVES: Factors contributing to arteriopathy in patients with Turner syndrome (TS) remain unclear. We assessed arterial stiffness in young, normotensive patients with TS and correlated arterial stiffness with vascular biomarkers, GH treatment and oestrogen exposure. Sixty-one patients with TS (mean age, 12·6 years; range 6·6-21·3 years) were matched for age and sex with 61 healthy peers. Associations between arterial stiffness and high-sensitivity C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), atrial NP (ANP), plasma aldosterone/plasma renin activity (PRA), IGF1 and IGFBP3 were examined after adjusting for well-established confounders of vascular disease. RESULTS: Carotid intima media thickness standard deviation score (SDS), arterial stiffness index SDS and incremental modulus of elasticity SDS were higher, and distensibility coefficient SDS was lower in patients with TS. The duration of GH treatment and oestrogen exposure was not associated with indices of arterial stiffness. TS patients had higher hsCRP, BNP and ANP. Plasma aldosterone/PRA, IGF1 and IGFBP3 were similar in patients and controls. Multivariable regression analyses (R(2) = 0·200-0·668, P < 0·01) showed that BNP was associated with all indices of arterial stiffness. We found that hsCRP was associated with distensibility coefficient SDS (ß = -0·16, P < 0·01). TS was independently associated with increased arterial stiffness (ß = 0·420-3·424, P < 0·001 for all, R(2) = 0·06-0·31). CONCLUSIONS: Young, normotensive TS patients had increased arterial stiffness than that of healthy peers. BNP, and possibly hsCRP, was independently associated with arterial stiffness in TS. Further research will determine any causal inference of these relationships.

Pelvic ultrasound findings in prepubertal girls with precocious adrenarche born appropriate for gestational age.

BACKGROUND: Precocious adrenarche (PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome (PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age (AGA) to healthy body mass index (BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents. SUBJECTS AND METHODS: We conducted a cross-sectional study on 56 AGA-born girls with PA (6·9 ± 0·6 years) and 33 BMI-matched prepubertal AGA-born peers (7·1 ± 1·0 years). Hormonal data, homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISIcomp ) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated. RESULTS: Precocious adrenarche girls had greater height and bone age-adjusted uterine length (UL; P = 0·01) and UL standard deviation score (SDS) (P = 0·02) than BMI-matched peers. Mean ovarian volume (MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups (P > 0·05). MOV and MOV SDS correlated with ISIcomp (r = -0·683, P < 0·001; r = -0·760, P < 0·001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance (P > 0·05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS (R(2) = 0·731, ß = -4·784, P = 0·001). CONCLUSIONS: Appropriate for gestational age-born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS.

Sitting height and sitting height/height ratio references for Turkish children.

UNLABELLED: Sitting height (SHt) measurements and sitting height/height (SHt/Ht) ratio are important criteria in the diagnosis of growth problems and particularly in the diagnosis of dysproportionate growth. It is known that body proportions are related to genetic influences and show variations among different populations. This study aimed to provide reference data on SHt and SHt/Ht ratios for Turkish children of ages 6-18 years. SHt measurements were performed on a sample of 1,100 boys and 1,020 girls between 6 and 18 years of age attending primary and secondary schools located in six different districts of Istanbul city. Criteria advanced by WHO for establishing reference standards for growth were observed in the study design. The sample consisted of a mixture of children measured only once and those measured at follow-up over different periods of time. Parallel to increase in Ht, SHt increased with age. Mean value for SHt/Ht ratio was 55-56% at ages 6 to 8.5 years in both sexes. In girls, this value started to decrease at age 11.5 years and remained between 53% and 54% thereafter. In the boys, a decrease to 52-53% was noted in the SHt/Ht ratio after age 12 years. In both sexes, SHt/Ht ratio decreased with puberty, demonstrating that growth in trunk length exceeded growth in limb length in midpubertal ages. These changes occurred at an earlier age in the girls. Values obtained for SHt/Ht ratios in Turkish children were high as compared to Dutch children and low as compared to Chinese children. CONCLUSION: This study, by providing reference data on sitting height and sitting height/height ratios in Turkish children of ages between 6 and 18 years, will be useful in the diagnosis and follow-up of children with growth problems. This study also supports the view that body proportions are influenced by genetic makeup.

Netherton syndrome associated with growth hormone deficiency.

Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by ichthyosiform scaling, hair abnormalities, and variable atopic features. Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. Growth retardation is a classic feature of NS, but growth hormone (GH) deficiency with subsequent response to GH therapy is not documented in the literature. It is proposed that a lack of inhibition of proteases due to a deficiency of LEKTI in the pituitary gland leads to the overprocessing of human GH in NS. Herein we report three patients with NS who had growth retardation associated with GH deficiency and responded well to GH therapy.

Are metabolic syndrome antecedents in prepubertal children associated with being born idiopathic large for gestational age?

INTRODUCTION: Being born large for gestational age (LGA) is a risk factor for development of metabolic syndrome (MS) in adolescents and adults. OBJECTIVE: To evaluate prepubertal children born idiopathic LGA to non-obese mothers without gestational diabetes or glucosuria with respect to the presence of MS antecedents. PATIENTS AND METHODS: We conducted a cross-sectional study to compare 40 (19 F) LGA-born prepubertal children of a mean age of 6.1 ± 2.5 yr and 49 (25 F) appropriate for gestational age (AGA)-born body mass index (BMI)-matched peers of a mean age of 5.4 ± 1.8 yr with respect to their anthropometric data, blood pressure measurements, fasting serum glucose and insulin levels, homeostasis model assessment-insulin resistance (HOMA-IR), and lipids and atherogenic index (AI) [triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)]. HOMA-IR > 2.5 was used to define IR. HDL-C ≤ 40 mg/dL and TG ≥ 110 mg/dL were used to define dyslipidemia. Both groups were further divided into subgroups as obese and non-obese according to their BMI percentiles and the analyses were repeated. RESULTS: Non-obese LGA children had higher waist circumference (WC) standard deviation scores (SDSs) than BMI-matched AGA-born peers (p = 0.024). There were no significant differences between pooled, obese and non-obese subgroups of LGA-born children and their AGA counterparts with respect to dyslipidemia and IR. AI was higher in non-obese LGA children than in AGA counterparts (p = 0.028). CONCLUSIONS: Non-obese idiopathic LGA-born children have higher AIs than AGA-born counterparts in the absence of IR. WC seems to be a good clinical screening tool in identifying at risk of non-obese LGA children. Further studies are needed to evaluate MS antecedents in idiopathic LGA-born children.

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis.

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man.

Vasculitis-like Palpable Purpuric Rash Induced by Decapeptyl in a Pediatric Patient Diagnosed Central Precocious Puberty

Central precocious puberty (CPP) is defined as the appearance of secondary sexual signs in girls younger than eight years of age or the onset of menarche before the age of 10 years. Gonadotropin-releasing hormone analogs (GnRHa) are the most effective therapy in CPP. Drug-induced hypersensitivity vasculitis is an inflammation of blood vessels, which may be due to the use of a number of pharmacologic agents. This case report describes drug-induced vasculitis in a girl being treated with Decapeptyl. A 7.25 year-old girl was admitted to Pediatric Endocrinology outpatients with premature breast development. She was diagnosed with CPP on the basis of physical examination and laboratory findings and tripoteline acetate (Decapeptyl®) treatment was initiated. She experienced multiple widespread skin rashes and mild abdominal pain with high temperature eight hours after the second dose of Decapeptyl. She was admitted to hospital with the diagnosis of drug-induced vasculitis and a single dose of intravenous methyl-prednisolone (1 mg/kg) and oral cetirizine was given. Her blood and urine analysis revealed no other organ involvement, other than skin. On the third day, the purpuric lesions began to resolve and had completely disappeared by the sixth day. Her treatment for CPP was switched to Depot Leuprolide acetate and she continued her treatment for two years uneventfully. To the best of our knowledge, this is the first report of a child with CPP experiencing drug-induced vasculitis due to tripotelin injection. Effective treatment may be continued by switching to an alternative gonadotropin releasing hormone analog.

Increased Carotid Intima-media Thickness and Its Association with Carbohydrate Metabolism and Adipocytokines in Children Treated with Recombinant Growth Hormone

Objective: Reports on the association between growth hormone (GH) therapy and cardiovascular risk factors in children are limited. This study aimed to evaluate carotid intima-media thickness (cIMT) in children treated with recombinant human GH (rhGH) and assess the effects of rhGH therapy and changes in serum carbohydrate metabolism, lipid profile and adipocytokines on cIMT. Methods: Seventy-one isolated idiopathic GH deficiency (GHD) children and 44 age- and sex-matched healthy controls were enrolled in this study. The study group was divided into two subgroups according to insulin resistance (IR) on oral glucose tolerance tests. Insulin secretion [homeostatic model assessment (HOMA) B, total insulin] and sensitivity (HOMA-IR, QUICKI, Matsuda) indices were calculated. cIMT was measured and the standard deviation scores (SDS) were calculated. Associations between cIMT-SDS and insulin secretion and sensitivity indices, serum lipid levels, adipocytokines (leptin, resistin, ghrelin), and other rhGH treatment-related factors were evaluated. Results: cIMT-SDS was increased in GHD children treated with rhGH compared to the controls [0.02 (2.27) vs. -1.01 (1.63), p=0.003]. cIMT-SDS did not differ between those children on rhGH treatment with or without IR. High cIMT-SDS was significantly associated with higher serum ghrelin levels and lower serum high density lipoprotein (HDL) levels (ß=0.491, p=0.001 and ß=-0.027, p=0.017), but not with BMI-SDS, blood pressure, insulin secretion and sensitivity indices, or the dose and duration of rhGH therapy. Conclusion: Our findings showed that GHD children treated with rhGH have increased cIMT. Alterations in carbohydrate metabolism were not associated with cIMT in children treated with rhGH. GH therapy per se appears to be associated with this increased cIMT but causality should be elucidated in further studies. cIMT also appears to be associated with higher ghrelin and lower HDL levels.

Long-Term Endocrinologic Follow-Up of Children with Brain Tumors and Comparison of Growth Hormone Therapy Outcomes: A SingleCenter Experience.

OBJECTIVE: Brain tumors in childhood carry a high risk for endocrine disorders due to the direct effects of the tumor and/or surgery and radiotherapy. Somatotropes are vulnerable to pressure and radiotherapy; therefore, growth hormone deficiency is one of the most frequent abnormalities. This study aimed to evaluate endocrine disorders and recombinant growth hormone treatment outcomes in brain tumor survivors. MATERIALS AND METHODS: In this study, 65 (27 female) patients were classified into 3 groups as craniopharyngioma (n = 29), medulloblastoma (n = 17), and others (n = 19). "Others" group included astrocytoma, ependymoma, germinoma, pineoblastoma, and meningioma patients. Anthropometric data and endocrine parameters of patients and their growth outcome with/without recombinant growth hormone therapy were collected from medical records, retrospectively. RESULTS: Mean age at the first endocrinological evaluation was 8.7 ± 3.6 years (range: 1.0- 17.1 years). Height, weight, and body mass index standard deviation score, mean ± standard deviation (median) values were -1.7 ± 1.7 (-1.5), -0.8 ± 1.9 (-0.8), and 0.2 ± 1.5 (0.4), respectively. Hypothyroidism (central 86.9%, primary 13.1%) was detected during follow-up in 81.5% of patients. Primary hypothyroidism in medulloblastoma (29.4%) was significantly higher compared to other groups (P = .002). The frequency of hypogonadotropic hypogonadism, central adrenal insufficiency, and diabetes insipidus was significantly high in the craniopharyngioma cases. CONCLUSION: In our study, endocrine disorders other than growth hormone deficiency were also frequently observed. In craniopharyngioma cases, the response to recombinant growth hormone therapy was satisfactory. However, there was no improvement in height prognosis during recombinant growth hormone therapy in medulloblastoma patients. A multidisciplinary approach to the care of these patients, referral for endocrine complications, and guidelines on when recombinant growth hormone therapy is required.

Precocious adrenarche in children born appropriate for gestational age: is there a difference between genders?

We aimed to determine whether precocious adrenarche (PA) has a different impact on screening tests for metabolic issues and pubertal timing in boys and girls born appropriate for gestational age (AGA). Puberty and initial metabolic screening results of 47 girls and 23 boys with PA born AGA followed up from our outpatient endocrinology clinic between May 2000 and October 2009 were reviewed. Initial anthropometric measurements except for body mass index standard deviation score (SDS) being higher in boys than girls (p = 0.01), bone age (BA) SDS, homeostasis model assessment of insulin resistance, and plasma lipids were similar between sexes. Hormone levels except for significantly higher dehydroepiandrosterone sulfate levels in boys than girls (p = 0.0006) were also similar between the sexes. BA SDS and BA/chronological age were significantly advanced (p < 0.05) with respect to initial evaluation in 28 girls at onset of gonadarche unlike the case in 13 boys with PA (p > 0.05). In conclusions, PA in children born AGA does not herald any significant differences with respect to adverse metabolic screening results between sexes, and it appears to be a discrete process from onset of puberty in girls unlike boys, in whom it is likely a variant of normal puberty.

Comparison of National Growth Standards for Turkish Infants and Children with World Health Organization Growth Standards

Objective: Using World Health Organization (WHO) standards in pediatric practice is still controversial in many countries. It is suggested that national growth charts best reflect the genetic and ethnic characteristics of a population. The aim of this study was to compare length/height, body weight, and body mass index (BMI) in healthy Turkish children of ages 0 to 18 with those proposed by WHO as the international growth standards. Methods: The data of Turkish children were collected from infant/child population aged 0-5 years (2391 boys, 2102 girls) and children of ages between 6-18 years (1100 boys, 1020 girls). For comparison, the 50th, 3rd, and 97th percentile curves for length/height, weight, and BMI in Turkish children were plotted together with respective WHO data. Results: Heights were essentially similar in the Turkish and WHO data at ages between 3-10 years. Turkish children were markedly taller compared to the WHO standards after the age of 10 years. Evaluation of the 3rd percentile data revealed that Turkish boys were shorter than the WHO subjects in the first 2 years of life. From 6 months of age, Turkish children showed higher weight for age values in the 3rd, 50th, and 97th percentiles. In all age groups between 6 months and 3 years, and in between 6-18 years of age, Z-score values, as well as the 50th, 15th, 85th, and 95th percentile values were higher in Turkish children. The differences were particularly noteworthy at ages 1-2 years and in the pubertal years. Conclusion: WHO growth standards do not reflect the growth of Turkish children and may substantially alter the prevalence of short stature and underweight in Turkish children in the 0-5 years age group. When assessing the nutritional and growth status of children, national growth standards may be more appropriate.

Characterization of a Novel Frameshift Mutation Within the TRPS1 Gene Causing Trichorhinophalangeal Syndrome Type 1 in a Kindred Cypriot Family.

Trichorhinophalangeal syndrome (TRPS) is an extremely rare autosomal dominant multisystem disorder characterized by craniofacial and skeletal abnormalities. Three subtypes of TRPS have been described: TRPS type I, TRPS type II, and TRPS type III. Mutations in the TRPS1 gene can cause both TRPS type I and TRPS type III. Therefore, the genotype-phenotype correlation is crucial to determine the subtype. The current family study from Cyprus involves affected patients from 4 generations who presented with alopecia, unoperated umbilical hernia, caput quadratum, long philtrum, depressed nasal bridge, frontal bossing, pes planus, beaked nose, and some deformities in hands and feet. Sequence analysis of the TRPS1 gene revealed a novel c.2854_2858del (p.Asn952ArgfsTer2) frameshift variant leading to a premature stop codon. To the best of our knowledge, we report here the first case of a Turkish Cypriot family of 4 generations with a novel frameshift mutation leading to truncated protein in the TRPS1 gene causing TRPS type I clinical phenotype. Overall, as the genotype and phenotype correlation in TRPSI is still uncertain and complex, the present outcome can enhance our knowledge of this complicated, rare, and severe genetic disorder.

Mutations in AR or SRD5A2 Genes: Clinical Findings, Endocrine Pitfalls, and Genetic Features of Children with 46,XY DSD

Objective: Androgen insensivity syndrome (AIS) and 5α-reductase deficiency (5α-RD) present with indistinguishable phenotypes among the 46,XY disorders of sexual development (DSD) that usually necessitate molecular analyses for the definitive diagnosis in the prepubertal period. The aim was to evaluate the clinical, hormonal and genetic findings of 46,XY DSD patients who were diagnosed as AIS or 5α-RD. Methods: Patients diagnosed as AIS or 5α-RD according to clinical and hormonal evaluations were investigated. Sequence variants of steroid 5-α-reductase type 2 were analyzed in cases with testosterone/dihydrotestosterone (T/DHT) ratio of ≥20, whereas the androgen receptor (AR) gene was screened when the ratio was <20. Stepwise analysis of other associated genes were screened in cases with no causative variant found in initial analysis. For statistical comparisons, the group was divided into three main groups and subgroups according to their genetic diagnosis and T/DHT ratios. Results: A total of 128 DSD patients from 125 non-related families were enrolled. Birth weight SDS and gestational weeks were significantly higher in 5α-RD group than in AIS and undiagnosed groups. Completely female phenotype was higher in all subgroups of both AIS and 5α-RD patients than in the undiagnosed subgroups. In those patients with stimulated T/DHT <20 in the prepubertal period, stimulated T/DHT ratio was significantly lower in AIS than in the undiagnosed group, and higher in 5α-RD. Phenotype associated variants were detected in 24% (n=18 AIS, n=14 5α-RD) of the patients, revealing four novel AR variants (c.94G>T, p.Glu32*, c.330G>C, p.Leu110=; c.2084C>T, p.Pro695Leu, c.2585_2592delAGCTCCTG, p.(Lys862Argfs*16), of these c.330G>C with silent status remained undefined in terms of its causative effects. Conclusion: T/DHT ratio is an important hormonal criterion, but in some cases, T/DHT ratio may lead to diagnostic confusion. Molecular diagnosis is important for the robust diagnosis of 46,XY DSD patients. Four novel AR variants were identified in our study.

Dental Age in Precocious and Delayed Puberty Periods.

OBJECTIVES: Precocious puberty indicates quick growth inception and delayed puberty indicates retardation in growth. This study aimed to investigate whether dental development is synchronous with somatic development. MATERIALS AND METHODS: In this study, 62 girls and 34 boys with precocious puberty aged 5 to 9, 29 girls with delayed puberty aged 13 to 16, and 43 boys with delayed puberty aged 14 to 17; 169 children (91 girls and 78 boys) with normal development were compared about their dental ages through their panoramic radiographs by using the Demirjian method and skeletal ages from hand-wrist radiographs by using Greulich-Pyle atlas. RESULTS: The findings showed that, in all cases, the dental age values were higher than chronologic and skeletal age values to a statistically significant degree. In the precocious puberty group, the dental age values were higher than chronologic age values to a statistically significant degree. In the delayed puberty group, the difference determined between the chronological age and the dental age was not found to be statistically significant. CONCLUSION: Given that the Demirjian method is inclined to make calculations that are higher than the chronological age, our findings suggest that the dental development was faster in the precocious puberty group and retarded in the delayed puberty group.