Adherence to Growth Hormone Treatment in Children During COVID-19 Pandemic

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the COVID-19 pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Materials and Methods: This was a multicenter survey study that was sent to pediatric endocrinologists in pandemic period (June 2021-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, and missed dose data and the causes in the recent year (after the onset of the pandemic) were queried. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% nonadherence). Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 mcg/kg, the annual growth rate was 1.15 SDS (min -2.74, max 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for nonadherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Nonadherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as nonadherence rate increased. Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

Clinical Features of Children with COVID-19 Infection: Single-Center Experience.

OBJECTIVE: Compared to adult studies, there are few epidemiological and clinical reports on coronavirus disease 2019 in children. We aimed to present the demographic, epidemiological, and clinical findings of hospitalized pediatric coronavirus disease 2019 patients. MATERIALS AND METHODS: Patients aged 0-18 years who were hospitalized between March and July 2020 due to severe acute respiratory syndrome coronavirus 2 infection were evaluated retrospectively. RESULTS: The mean age was 90.2 ± 67.5 (7-24) months and 23 (51%) were female. Clinical presentation was asymptomatic in 15 cases (33.3%), mild/moderate in 26 cases (57.8%), and severe/critical in 4 cases (8.9%). Three (6.6%) of the patients had chronic medical conditions that placed them in the high-risk group for coronavirus disease 2019. The source of infection was household transmission in 29 cases (64.4%). The most common symptoms were cough, fever, and fatigue. Mean serum lactate, C-reactive protein (CRP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were significantly higher in severe/criti- cal patients compared to the other two groups (P < .05). severe acute respiratory syndrome coronavirus 2 negativity in control swabs (n=26) occurred at a mean of 10.6 ± 2.9 days after symptom onset. Forty-three patients (95.6%) were followed in the ward and 2 (4.4%) were admitted to the intensive care unit. CONCLUSION: Children aged 0-18 years constituted a very small proportion of coronavirus disease 2019 reverse transcription-polymerase chain reaction -positive cases. Asymptomatic carriage of SARS- CoV-2 by a large proportion of children seems to be a major factor driving community spread. Some children with coronavirus disease 2019 may also present neurological findings. coronavirus disease 2019 infection is more severe in patients with comorbidities, and support therapy is important in these patients.

Plasma renin, aldosterone, and urinary prostaglandin E2 levels in children with hypocalcemia due to vitamin D deficiency rickets.

We investigated the effect of hypocalcemia on plasma renin, aldosterone, and urine PGE2 levels in children with vitamin D deficiency rickets (VDDR). In the study group, 25 patients with VDDR-induced hypocalcemia were treated with a single dose of 150,000-300,000 IU cholecalciferol and 50 mg/kg/day elemental Ca for 10 days. On any day between 21th and 30th days after the treatment, the patients' clinical, biochemical and radiologic findings were re-evaluated. The healthy children with the same sex and similar age as the study group comprised the control group. Plasma sodium (Na), potassium (K), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), 25- hydroxy vitamin D (25OHD), renin, aldosterone; and urinary Ca, creatinine (Cr) and prostaglandin E2 (PGE2) levels were measured in both the study (pre-treatment and post-treatment) and the control group. Plasma Ca, P, 25OHD and renin levels and urinary PGE2/Cr ratio in the post-treatment group were significantly higher than those in the pre-treatment group while K, ALP, and PTH concentrations were significantly lower. Plasma ALP and PTH levels in pre-treatment group were significantly higher than in the control group while Ca, P, 25OHD, aldosterone and renin concentrations and urinary PGE2/Cr ratio were significantly lower. Post-treatment plasma Ca level was significantly decreased in normal limits compared to the control group while other biochemical parameters were not different from the control group. Plasma Ca concentration was positively correlated with renin level and urinary PGE2/Cr ratio. The findings suggest that hypocalcemia may inhibit the production of renin, aldosterone and PGE2 and a blunt aldosterone secretion may develop even after recovery from hypocalcemia.

Multisystem inflammatory syndrome in children associated with COVID-19 in 101 cases from Turkey (Turk-MISC study).

AIM: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. METHODS: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. RESULTS: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 µg/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. CONCLUSION: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management.

COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group.

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.

Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovaries. Its pathogenesis is still unclear. This study aimed to investigate the relationship between kisspeptin, leptin, neuropeptide Y (NPY), and neurokinin B (NKB) levels for evaluating the pathogenesis of PCOS. METHODS: Levels of these parameters were analyzed in 20 patients with PCOS, and 16 healthy adolescents. RESULTS: Serum NPY levels were significantly higher in the obese and non-obese PCOS group (p<0.01). There was a negative correlation between the kisspeptin and the NKB levels (p<0.01) in the PCOS group but not in the control group. This negative correlation was also found in both PCOS groups (p<0.01). In the obese PCOS group, serum kisspeptin levels were significantly lower than the control and non-obese PCOS groups (p<0.05) although serum leptin and NPY levels were significantly higher in the obese PCOS group (p<0.01). CONCLUSIONS: The high NPY levels in both obese and non-obese patients with PCOS indicate that NPY plays a role in the pathogenesis independently from obesity. Significantly high leptin and low kisspeptin levels in the obese PCOS group suggested that they may be associated with obesity rather than PCOS.

Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency.

CONTEXT: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. OBJECTIVE: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. METHODS: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. RESULTS: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. CONCLUSION: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

The Relationship between Psychopathology, Self-esteem, Body Perception and Serum Sex Steroids in Pubertal Gynecomastia.

OBJECTIVE: The current study aimed to investigate the psychopathology behind gynecomastia and potential associated problems regarding self-esteem and body perception, and the relationships of these variables with sex steroid levels in adolescents with pubertal gynecomastia. METHODS: The study included 50 normal weight male adolescents aged between 11 and 18 years with gynecomastia but without any chronic organic pathology, and 50 healthy pubertal male adolescents matched for age. The adolescents underwent psychopathology assessment by Development and Well-Being Assessment interviews; self-esteem was assessed using the Rosenberg Self-Esteem Scale; body perception was evaluated using the Body Image Perception Scale, and the relationship between these variables and sex steroid levels were explored. RESULTS: The results of the study revealed that the gynecomastia group had significantly greater internalization disorder (X2 = 12.96, p < 0.001), and impairments in self-esteem (z = -1.975, p = 0.024) and body perception (z = -2.286, p = 0.022), and these variables were correlated with the gynecomastia stage. In the study group, cortisol levels were significantly higher (z = -2.330, p = 0.02) in adolescents with internalization disorder compared to those without, and cortisol levels increased in parallel with increased gynecomastia duration (r = 0.386, p = 0.006). CONCLUSION: In our study, we found that gynecomastia, depending on its stage, may lead to internalization disorder and impair self-esteem and body perception. It was found that there was no direct relationship between these parameters and sex steroids in pubertal gynecomastia, except for high cortisol levels in adolescents with internalization disorder.

Effectiveness of lopinavir/ritonavir on COVID-19-related pneumonia in a child with COVID-19-associated Kawasaki disease.

The large outbreak of coronavirus disease 2019 (COVID-19) is spreading all over the world rapidly. There have recently been publications in the literature regarding the relationship between COVID-19 and Kawasaki disease, but there is no sufficient knowledge about the treatment and follow-up.

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: Outcomes of Extended Pilot Study in 241,083 Infants

Objective: Turkish Directorate of Public Health introduced the first pilot screening program for congenital adrenal hyperplasia (CAH) in four Turkish cities in 2017, and in 2018 extended the program, with a slight change in screening strategy, to fourteen cities. To evaluate the performance of the extended study and update previously reported outcomes. Methods: Retrospective, descriptive study. Neonates of ≥32 gestational weeks and ≥1500 gr birth weight from fourteen cities, born between May-December 2018, were included. Screening protocol included one sample, two-tier testing as applied in the previous pilot study. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. Cases with positive initial screening underwent second tier testing by steroid profiling in DBS using liquid chromatographyt-andem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.7 (increased from ≥0.5 in the earlier pilot study) were referred to pediatric endocrinology clinics for diagnostic assessment. Results: In the evaluated period, 241,083 newborns were screened. 12,321 (5.11%) required second-tier testing and 880 (0.36%) were referred for clinical assessment, twenty of whom were diagnosed with CAH (10 females, 10 males). Sixteen were diagnosed as classical 21-hydroxylase deficiency (21-OHD) CAH (12 with salt-wasting and four with simple virilising CAH), and four cases were identified with 11ß-OHD CAH. No case of salt-wasting CAH was missed by neonatal screening (sensitivity was 100%). The incidence of classical 21-OHD and 11ß-OHD in the screened population was 1:15,067 and 1:60,270, respectively. Conclusion: Turkish neonatal CAH screening effectively led to earlier diagnosis of 21-OHD and 11ß-OHD, using steroid profiling as a second-tier test. This will result in improved care of these patients in the future.

The effect of therapy on plasma ghrelin and leptin levels, and appetite in children with iron deficiency anemia.

Background It is known that iron deficiency anemia effects appetite and growth negatively. The aim of this study was to investigate the effect of iron therapy on appetite, growth and plasma ghrelin and leptin levels in children aged between 12 and 24 months with isolated nutritional iron deficiency anemia. Methods Iron deficiency anemia was diagnosed by clinic and laboratory findings. All 19 cases were given 5 mg/kg/day iron therapy for 3 months. Results The mean plasma ghrelin level was 936.7±428.8 pg/mL before therapy and it increased to 1284.7±533.3 pg/mL (p<0.001) while the mean plasma leptin level decreased from 3.4±1.6 ng/mL to 1.9±1.0 ng/mL (p<0.01) after therapy. The amount of daily caloric intake, carbohydrate and protein intake were significantly increased after therapy (p<0.001). Δ body weight was correlated with plasma ghrelin levels before and after therapy significantly. Conclusions In conclusion, the findings of this study indicate that plasma ghrelin level increases and leptin level decreases and growth accelerates because of an increase in appetite and daily calories, carbohydrate and protein amount in children with nutritional iron deficiency anemia after iron therapy. The increase in appetite and acceleration on growth in iron deficiency anemia might result from decreased leptin and increased plasma ghrelin levels. The most important finding of this study is significantly increased plasma ghrelin levels after iron therapy, and this finding might be related to both the improved appetite and catch-up growth.

Comparison of Treatment Regimens in Management of Severe Hypercalcemia Due to Vitamin D Intoxication in Children

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (rs=0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

Serum vitamin D and vitamin D-binding protein levels in mother-neonate pairs during the lactation period.

BACKGROUND: To determine longitudinally the relationship between serum 25-hydroxyvitamin D (vitamin D) and vitamin D-binding protein (DBP) levels in mother-neonate pairs and evaluate the efficiency of prophylactic vitamin D on lactation days 45-60. METHODS: Mother-neonate pairs whose serum calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (ALP), and parathyroid hormone (PTH) levels were in normal ranges on postpartum/postnatal days 5-10 were classified into two groups by their serum vitamin D concentrations (Group A: < 10 ng/ml and Group B: > 20 ng/ml). Both maternal and neonatal Ca, P, Mg, ALP, and PTH concentrations in group A and B were not different. Maternal and neonatal serum DBP levels were measured in two groups. The mother-neonate pairs in both groups were given 400 IU/d vitamin D orally. The same biochemical markers in group A were remeasured on days 45-60 of the lactation period. RESULTS: In group A, the mean maternal and neonatal vitamin D levels on postpartum/postnatal days 5-10 were significantly lower and the DBP levels were significantly higher than those in group B (P = 0.000; P = 0.000 and P = 0.04; P = 0.004, respectively). On lactation days 45-60, the maternal and neonatal DBP concentrations were not different from those on postpartum/postnatal days 5-10. However, the maternal and neonatal vitamin D levels were significantly increased (P = 0.000 and P = 0.000, respectively), while the neonatal PTH concentrations were significantly decreased (P = 0.000). The maternal and neonatal vitamin D concentrations were negatively correlated with their DBP concentrations (P = 0.048 and P = 0.002, respectively). CONCLUSION: High maternal and neonatal DBP levels may lead to an incorrect low estimate of the true Vitamin D concentration. In this case, only prophylactic vitamin D (400 IU/d) is indicated for mothers and their infants.

Infantile Nephropathic Cystinosis: A Novel CTNS Mutation.

Cystinosis is a rare autosomal recessive metabolic disorder characterized by the accumulation of cystine in lysosomes, which results from defects in the carrier-mediated transport protein encoded by the CTNS gene. Infantile nephropathic cystinosis (INC) is one of the major complications of cystinosis. It is characterized by findings of Fanconi's syndrome within the first year of life. Here we report two patients with INC presenting with signs of Fanconi's syndrome and describe a novel CTNS mutation.

The Relationship Between Skinfold Thickness and Leptin, Ghrelin, Adiponectin, and Resistin Levels in Infants of Diabetic Mothers.

This study aimed to investigate the relationship between skinfold thickness and serum leptin, ghrelin, adiponectin, and resistin levels in infants of diabetic mothers. Biochemical parameters were also similar for the two groups (infants of diabetic mothers and controls) (p > 0.05). We confirmed that there was a negative correlation between birth weight and serum ghrelin level (p < 0.05) in the two groups. When it was evaluated for control newborns, a positive correlation between abdominal circumference and serum resistin level was found in the controls (p < 0.05). Our results indicate that gestational diabetes by appropriate diet or insulin treatment may be effective in the protection of fetuses of diabetic mothers from the negative effects of gestational diabetes. Ghrelin alone was negatively correlated with birth weight. This negative correlation could be potentially advantageous to infants, because a reduction in appetite might prevent excessive food intake and postnatal weight gain.

Severe Short Stature in Two Siblings as the Presenting Sign of ACP5 Deficiency.

BACKGROUND: ACP5 deficiency is known to cause spondyloenchondrodysplasia (SPENCD), which is characterized by various autoimmune and neurological symptoms in addition to short stature. METHODS: Two siblings from a consanguineous Turkish family, a girl aged 13 years (P1) and a boy aged 8 years (P2), presented to their endocrinologist with progressive growth failure and severe short stature (-5 SDS). They had no comorbid conditions and, on physical examination, there were no signs of an overt skeletal dysplasia with normal appearance of extremities. Other than a low baseline IGF-1, extensive laboratory workup, including growth hormone stimulation and IGF-1 generation tests, was normal. Exome sequencing was performed. RESULTS: Exome sequencing identified the presence of a homozygous frameshift mutation (p.Ser258Trpfs*39) in ACP5 in both siblings, which was confirmed by Sanger sequencing. This specific mutation has previously been described in patients with SPENCD. Additional workup in the two siblings showed distinct features of skeletal dysplasia on X-rays consistent with SPENCD, but none of the common autoimmune or neurological abnormalities associated with this condition. CONCLUSION: Severe short stature can be the only presenting sign of ACP5 deficiency and the latter could therefore be considered as a rare cause in the differential diagnosis of severe, proportionate growth failure.

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.

Leptin and neuropeptide Y levels in newborns.

AIM: Several studies have investigated leptin and neuropeptide Y (NPY) levels in children, but the information for newborns in the literature is limited. The purpose of this study was to determine leptin and NPY levels in 14- to 28-day-old newborns. MATERIALS AND METHODS: This prospective study was performed in Atatürk University Medical Faculty Research Hospital Neonatal Clinic, Erzurum, Turkey between July and December, 2014. Sixty-two 14- to 28-day-old neonates, 26 female and 36 male, were included. Age, height, and body weight of the patients were recorded. Feeding status was also recorded. The newborns were divided into two groups--those receiving breastfeeding only and those receiving breastfeeding and formula. Plasma leptin levels were measured using enzyme amplified sensitivity immunoassay (EASIA). RESULTS: The mean leptin level in 14- to 28-day-old female neonates was 4.25 ± 3.08 ng/mL, and the mean NPY level was 24.79 ± 9.87 ng/mL. The mean leptin level in 14- to 28-day male neonates was 3.49 ± 2.52 ng/mL, and the mean NPY level was 25.80 ± 9.58 ng/mL. No significant difference was determined between leptin (p=0.228) or NPY (p=0.144) in terms of feeding status. No significant difference was also observed between the sex in terms of leptin or NPY levels (leptin p=0.775 and NPY p=0.687). CONCLUSION: There were no differences in terms of feeding status and sex in leptin and NPY levels in the neonatal period.

Turner syndrome and associated problems in Turkish children: a multicenter study.

OBJECTIVE: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. METHODS: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. RESULTS: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. CONCLUSION: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan.

Fasting and postprandial glucose, insulin, leptin, and ghrelin values in preterm babies and their mothers: relationships among their levels, fetal growth, and neonatal anthropometry.

OBJECTIVE: To investigate relationship between anthropometric values of premature babies with their's glucose, insulin, leptin, and ghrelin at birth and on day 15. METHODS: We analyzed fasting and postprandial glucose, insulin, leptin, and ghrelin levels at birth and on day 15 in babies born prematurely between 24 and 37 weeks, and who did not have serious problems aside from prematurity at birth. RESULTS: Fasting glucose, insulin, leptin and ghrelin values of babies at birth and on day 15 were significantly lower than postprandial values (all p values p < 0.001). There were positive correlations between the mean insulin, leptin, and ghrelin levels with the gestational age, birth weight, body mass index, head circumference of babies at birth, and anthropometric values on day 15 (all r values > 0.400, all p values < 0.05). Fasting glucose, leptin, and ghrelin values of mothers birth were significantly lower than post-prandial values (all p values p < 0.05). CONCLUSIONS: The positive correlations between the insulin, leptin, and ghrelin values of babies at birth with gestational age and anthropometric values suggest that both hormones play important roles in fetal and neonatal growth and development.