Early postnatal metabolic profile in neonates with critical CHDs.

BACKGROUND: Cyanotic CHD is a life-threatening condition that presents with low oxygen saturation in the newborn period. Hypoxemia might cause alterations in the metabolic pathways. In the present study, we aimed to evaluate the early postnatal amino acid and carnitine/acylcarnitine profiles of newborn infants with cyanotic CHD. METHODS: A single centre case-control study was conducted. Twenty-seven patients with cyanotic CHD and 54 healthy newborn controls were enrolled. As part of the neonatal screening programme, results of amino acid and carnitine/acylcarnitine were recorded and compared between groups. RESULTS: Twenty-seven neonates with cyanotic CHD and 54 healthy newborns as controls were enrolled in the study. Cyanotic CHD neonates had higher levels of alanine, phenylalanine, leucine/isoleucine, citrulline, ornithine, C5, C5-OH; but lower levels of C3, C10, C12, C14, C14:1, C16, C16.1, C18, C5-DC, C6-DC, C16-OH, C16:1-OH when compared with the healthy controls. CONCLUSION: This study showed that there are differences between patients with cyanotic CHD and healthy controls in terms of postnatal amino acid and carnitine/acylcarnitine profiles.

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features.

Biallelic loss of function mutations in the CLDN16 gene cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and chronic kidney disease. Here we report two cases of FHHNC with diverse clinical presentations and hypercalcemia in one as a novel finding. Pt#1 initially presented with urinary tract infection and failure to thrive at 5.5 months of age to another center. Bilateral nephrocalcinosis, hypercalcemia (Ca: 12.2 mg/dl), elevated parathyroid hormone (PTH) level, and hypercalciuria were detected. Persistently elevated PTH with high/normal Ca levels led to subtotal-parathyroidectomy at the age of 2.5. However, PTH levels remained elevated with progressive deterioration in renal function. At 9-year-old, she was referred to us for evaluation of hyperparathyroidism and, hypomagnesemia together with hypercalciuria, elevated PTH with normal Ca levels, and medullary nephrocalcinosis were detected. Compound heterozygosity of CLDN16 variants (c.715G>A, p.G239R; and novel c.360C>A, p.C120*) confirmed the diagnosis. Pt#2 was a 10-month-old boy, admitted with irritability and urinary crystals. Hypocalcemia, hypophosphatemia, elevated PTH and ALP, low 25(OH)D levels, and radiographic findings of rickets were detected. However, additional findings of hypercalciuria and bilateral nephrocalcinosis were inconsistent with the nutritional rickets. Low/normal serum Mg levels suggested the diagnosis of FHHNC which was confirmed genetically as a homozygous missense (c.602G > A; p.G201E) variant in CLDN16. Yet, hypocalcemia and hypomagnesemia persisted in spite of treatment. In conclusion, FHHNC may present with diverse clinical features with mild hypomagnesemia leading to secondary hyperparathyroidism with changing Ca levels from low to high. Early and accurate clinical and molecular genetic diagnosis is important for proper management.

Hypoglycemia is common in children with cystic fibrosis and seen predominantly in females.

OBJECTIVE: To determine the prevalence of hypoglycemia in children and adolescents with cystic fibrosis (CF) in 2-hour oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) under free-living conditions. RESEARCH DESIGN AND METHODS: Height, weight, body mass index (BMI), hemoglobin A1c (HbA1c), and Forced expiratory volume (FEV1%) were measured in children with CF (aged 5-18 years). Following OGTT, CGM was installed for 3 days. The total hypoglycemic and hyperglycemic time (%) during 3 days was measured. Subjects were categorized according to hypoglycemic time <3% (hypo -) and ≥3% (hypo +). Each category was further divided according to hyperglycemic time <3% (hyper -) or ≥3% (hyper +). RESULTS: OGTT and CGM were sequentially performed in 45 CF patients. The frequency of hypoglycemia in OGTT and hypoglycemic time ≧3% of CGM were 13.3% and 27.5%, respectively. After 5 cystic fibrosis-related diabetes (CFRD) subjects were excluded, the number of subjects in each subgroup was 17 (hypo-/hyper-), 12 (hypo-/hyper+), 6 (hypo+/hyper-), and 5 (hypo+/hyper+). Significantly higher insulin at 120 minutes was observed in OGTT in (hypo+/hyper-), as compared with subgroup (hypo-/hyper-) (P = .018). Total insulin levels were also significantly higher in (hypo+/hyper-), than (hypo-/hyper-), but were similar to those in the healthy control group (P = .049 and P = .076, respectively). There was a female predominance in hypoglycemic subjects both in OGTT and subgroup (hypo+/hyper-) in the CGM group (P = .033 and P = .033, respectively). FEV1 was significantly lower in hypo + group as a whole, and (hypo+/hyper+) subgroup than in (hypo-/hyper-), (P = .044 and P = .042, respectively); the difference was independent of body mass index-standard deviation score (BMI-SDS) (P = .15 and P = .12, respectively). CONCLUSION: The frequency of hypoglycemia in children with CF was higher in CGM than that in OGTT. Insulin secretion was delayed and total insulin levels increased in the hypoglycemic patients. Glucose instability/hypoglycemia is associated with poorer lung function in patients with CF, independent of nutritional status.

The assessment of peripapillary retinal nerve fiber layer and macular ganglion cell layer changes in obese children: a cross-sectional study using optical coherence tomography.

PURPOSE: To investigate the relationship between the obesity and optical coherence tomography (OCT) parameters. METHODS: We studied 54 obese and 33 non-obese children and adolescents. Obesity was defined as BMI higher than 95th percentile (BMI SDS > 1.64). OCT measurements were performed in all participants. Anthropometric and biochemical variables were compared with OCT parameters of 174 eyes. RESULTS: In obese children, in all quadrants retinal nerve fiber layer (RNFL) thicknesses were significantly lower than non-obese children, and also ganglion cell-inner plexiform layer thicknesses in inferior and superiortemporal quadrants were significantly lower in the obese group. BMI SDS, insulin, HOMA-IR and triglyceride levels were negatively correlated with RNFL thickness, significantly (r = -0.386, p < 0.001; r = -0.229, p = 0.002; r = -0.188, p = 0.013; and r = -0.301, p = 0.000; respectively) in all subjects. CONCLUSIONS: Thinning in RNFL was detected in normal-looking discs of obese children, and this thinning negatively correlated with BMI SDS. Further studies including large series are needed to clarify whether obesity has an effect on RNFL thickness.

GCK gene mutations are a common cause of childhood-onset MODY (maturity-onset diabetes of the young) in Turkey.

OBJECTIVE: Inactivating heterozygous mutations in the GCK gene are a common cause of MODY and result in mild fasting hyperglycaemia, which does not require treatment. We aimed to identify the frequency, clinical and molecular features of GCK mutations in a Turkish paediatric cohort. DESIGN AND PATIENTS: Fifty-four unrelated probands were selected based on the following criteria: age of diagnosis ≤17 years, family history of diabetes in at least two generations, anti-GAD/ICA negative, BMI<95.p and follow-up with diet, oral antidiabetic drug or low-dose insulin treatment (≤0·5U/kg/d). A MODY probability score (www.diabetesgenes.org) was calculated and 21 patients with a score ≥75%, HbA1c levels ≤7·5% (58·5 mmol/mol) and fasting blood glucose (FBG) levels 99-145 mg/dl (5·5-8·0 mmol/l) were selected for Sanger sequencing of the GCK gene. Targeted next-generation sequencing for all known monogenic diabetes genes was undertaken for any patient without a GCK gene mutation. RESULTS: GCK gene mutations (pathogenic or likely pathogenic variants) and a novel intronic variant of uncertain significance (c.208 + 3A>T) were identified in 13/54 probands (24%). Twelve of these patients had a MODY probability score ≥75%. FBG level and 2-h glucose level in OGTT were 123 ± 14 mg/dl (6·8 ± 0·7 mmol/l) (107-157 mg/dl) and 181 ± 30 mg/dl (10·1 ± 1·6 mmol/l) (136-247 mg/dl), respectively. Average of glucose increment in OGTT was 58 ± 27 mg/dl (3·2 ± 1·5 mmol/l) (19-120 mg/dl), and mean HbA1c level was 6·5 ± 0·5% (47·5 ± 5·5 mmol/mol) (5·9-7·6%). Five novel missense mutations were identified (p.F123S, p.L58P, p.G246A, p.F419C, and p.S151C). Two patients treated with low-dose insulin before the molecular analysis were able to stop treatment. CONCLUSIONS: Approximately 1 in 4 MODY cases in this Turkish paediatric cohort have a GCK mutation. Selection of patients for GCK gene analysis using the MODY probability score was an effective way of identifying most (11/12) patients with a GCK mutation.

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 insulin detemir doses are required for the similar glycemic control: comparison of insulin detemir and glargine in children with type 1 diabetes mellitus.

OBJECTIVE: We aimed to compare hemoglobin A1c (HbA1c), total and basal insulin doses, basal insulin injection frequencies, and body mass index (BMI) in children with type 1 diabetes mellitus (T1DM) who are receiving detemir and glargine as basal insulin in a basal-bolus therapy. METHOD: This retrospective study included 117 (53 females) children and adolescents with T1DM older than 4 yr of age, minimum diabetes duration of 2 yr, and receiving basal-bolus insulin regimen (at least 4 injections/d, insulin aspart or lispro as bolus insulin). Comparisons were made for those receiving insulin detemir (n = 32) or glargine (n = 85) as the basal insulin. RESULTS: Age, pubertal status, BMI standard deviation scores, and diabetes duration were similar in detemir and glargine groups. Glycemic control was similar in both groups (HbA1c levels 8.9 ± 2.1% vs. 8.5 ± 1.7% for detemir and glargine, respectively; p = 0.497). Both mean basal insulin (0.52 vs. 0.41 U/kg/d, p < 0.001) and mean total daily insulin (1.11 vs. 0.93 U/kg/d, p < 0.001) doses were higher in the detemir group. Furthermore, higher ratio of twice-daily basal insulin injection was detected in the detemir group (62.5 vs. 32.9% p = 0.004). Subgroup analysis according to pubertal status, or the number of daily basal injections showed similar results. CONCLUSION: Insulin detemir provides similar glycemic control with glargine, but, approximately 27% higher mean basal and 19% higher mean total insulin doses with two-fold more twice-daily basal insulin injection requirement.

Infantile loss of teeth: odontohypophosphatasia or childhood hypophosphatasia.

Hypophosphatasia is a hereditary disorder characterized by a deficiency of serum and bone alkaline phosphatase (ALP) activity and defective skeletal mineralization. It is caused by a loss of function mutations in the tissue nonspecific ALP gene (TNSALP) encoding the tissue nonspecific alkaline phosphatase. A 4-year-and-8-month-old girl presented with premature exfoliation of the anterior incisors and canines. Very low ALP level (27 IU/ml) suggested the diagnosis of hypophosphatasia, which was supported by an elevated urine phosphoethanolamine/Cr of 84 µmol/mmol (reference range, <25 µmol/mmol) and serum pyridoxal-5'-phosphate of 393 µg/L (reference range, 3.6-18 µg/L). The phenotype of the patient was subsequently classified as mild childhood hypophosphatasia. TNSALP gene sequencing revealed the homozygous c.382 G > A (p.V128M) mutation. This mutation was previously observed in a series of patients with severe hypophosphatasia, pointing out the possible role of other genetic or environmental factors in the modulation of the hypophosphatasia phenotype.

Interdisiplinary and intraobserver reliability of the Greulich-Pyle method among Turkish children.

OBJECTIVES: Greulich-Pyle (GP) is one of the most used method for bone age determination (BAD) in various orthopedic, pediatric, radiological, and forensic situations. We aimed to investigate the inter- and intra-observer reliability of the GP method between the most relevant disciplines and its applicability to the Turkish population. METHODS: One-hundred and eighty (90 boys, 90 girls) patients with a chronological age younger than 18 (mean 9.33) were included. X-rays mixed by the blinded investigator were evaluated by two orthopedists, two radiologists, and two pediatric endocrinologists to determine skeletal age according to the GP atlas. A month later the process was repeated. As a statistical method, Paired t-test was used for comparison, an Intraclass Correlation Coefficients test was used for reliability and a 95 % confidence interval was determined. Results were classified according to Landis-Koch. RESULTS: All results were consistent with chronological age (p<0.001), according to the investigators' evaluations compared with chronological age. At the initial evaluation, the interobserver reliability of the method was 0.999 (excellent); at the second evaluation, the interobserver reliability was 0.997 (excellent). The intra-observer reliability of the method was 'excellent' in all observers. When results were separately evaluated by gender, excellent intraobserver correlation and excellent correlation with chronological age were found among all researchers (>0.9). When X-rays were divided into three groups based on age ranges and evaluated, 'moderate' and 'good' correlations with chronological age were obtained during the peripubertal period. CONCLUSIONS: The GP method used in skeletal age determination has excellent inter- and intra-observer reliability. During the peripubertal period, potential discrepancies in bone age assessments should be kept in mind. This method can be used safely and reproducibly by the relevant specialists.

Challenges in the Management of a 7-Year-Old Child with Thyrotropin-Secreting Pituitary Adenoma and the Review of the Literature.

INTRODUCTION: Thyrotropin-producing pituitary adenoma (TSHoma) is a very rare disease, representing less than 1% of the pituitary tumours and presenting with elevated thyroid hormones and normal/high TSH concentrations. CASE PRESENTATION: A 7-year-old boy with nervousness was referred by his psychiatrist for elevated free T4, T3, and TSH levels. Initial evaluation revealed an elevated α-subunit. Pituitary magnetic resonance imaging (MRI) demonstrated a macroadenoma. The patient underwent a trans-sphenoidal tumour resection (TSS) which showed positive immunohistochemical staining for TSH, growth hormone, and prolactin in tumoral tissue. Euthyroidism was achieved for 1 year after TSS, then recurrence of tumour with elevated TSH and thyroid hormone levels necessitated a re-operation with TSS followed by gamma-knife radiosurgery. The euthyroid state was achieved and lasted for 2.5 years this time, but due to the recurrence, medical treatment had been commenced with cabergoline and octreotide. Euthyroidism was maintained for the last 4 years on monthly octreotide treatment. A repeat MRI demonstrated no pituitary mass, but a mass in the sphenoidal sinus had been detected. Removal of this mass by surgery did not achieve euthyroidism. 68Ga-DOTA-TATE positron emission tomography/computed tomography showed residual tissue extending from the pituitary region to the sphenoid sinus. The patient's bone age was advanced by 2 years at diagnosis which became 4 years in 1 year after the diagnosis and remained so throughout follow-up, leading to a final height of -3.3 SDS below his target height at the age of 16 years. CONCLUSION: The diagnosis, treatment, and follow-up of TSHomas are challenging, and short stature due to accelerated bone maturation is a complication of paediatric TSHomas.

Effect of iron supplementation on development of iron deficiency anemia in breastfed infants.

This trial aimed to investigate the effect of iron supplementation on the development of iron deficiency anemia. The study encompassed 6-month-old infants who had been exclusively breastfed in the first 4 months of life. Infants in the supplemented group were given 1 mg kg(-1 )day(-1) ferrous sulfate for 6 months starting at 6 months of age. Blood samples were taken at age 12 months. A 3-day-diet was evaluated at 1 year of age. Data of 51 infants in the supplemented and 54 infants in the control group were analyzed. Mean hemoglobin values were similar in the two groups at the age of 12 months. Mean ferritin level of the supplemented group was significantly higher than that of the control. There was a significant positive correlation between dietary iron intake and hemoglobin levels. Nutrition might be more important than iron supplementation in preventing iron deficiency anemia during infancy.

A novel deletion involving the first GNAS exon encoding Gsα causes PHP1A without methylation changes at exon A/B.

Individuals affected by pseudohypoparathyroidism type 1A (PHP1A) display hyperphosphatemia and hypocalcemia despite elevated PTH levels, as well as features of Albright Hereditary Osteodystrophy (AHO). PHP1A is caused by variants involving the maternal GNAS exons 1-13 encoding the stimulatory G protein α-subunit (Gsα). MLPA and aCGH analysis led in a male PHP1A patient to identification of a de novo 1284-bp deletion involving GNAS exon 1. This novel variant overlaps with a previously identified 1438-bp deletion in another PHP1A patient (ref. Li et al. (2020) [13], patient 2) that extends from the exon 1 promoter into the up-stream intronic region. This latter deletion is associated with reduced methylation at GNAS exon A/B, i.e. the differentially methylated region (DMR) that is demethylated in most pseudohypoparathyroidism type 1B (PHP1B) patients. In contrast, genomic DNA from our patient revealed no evidence for an epigenetic GNAS defect as determined by MS-MLPA and pyrosequencing. These findings thus reduce the region, which, in addition to other nucleotide sequences telomeric of exon A/B, may undergo histone modifications or interacts with transcription factors and possibly as-yet unknown proteins that are required for establishing the maternal methylation imprints at this site. Taken together, nucleotide deletions or changes within an approximately 1300-bp region telomeric of exon A/B could be a cause of PHP1B variants with complete or incomplete loss-of-methylation at the exon A/B DMR. In addition, when investigating patients with suspected PHP1A, MLPA should be considered to search for structural abnormalities within this difficult to analyze genomic region comprising GNAS exon 1.

Rapid molecular diagnosis of ALB gene variants prevents unnecessary interventions in familial dysalbuminemic hyperthyroxinemia.

OBJECTIVES: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition caused by heterozygous gain-of-function mutations in the human ALB gene. CASE PRESENTATION: We report, a three-year-old boy with FDH due to p.R242P (or p.R218P without signal peptide) mutation in the ALB gene with a phenotype characterized by extremely high serum total and free thyroxine concentrations. His parents had normal thyroid function tests (TFT), so the mutation detected in this patient is assumed "de novo". Although the most frequent variant was p.R242H in Caucasians and p.R242P in Japanese, our patient had p.R242P variant. CONCLUSIONS: Early identification of FDH is fundamental to prevent unnecessary repeats of TFT with different methods. We encourage the ALB gene hot spot sequencing initially and indicate that this molecular diagnosis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.

Neonatal Problems and Infancy Growth of Term SGA Infants: Does "SGA" Definition Need to Be Re-evaluated?

Introduction: The exact definition of small-for-gestational-age (SGA) infant is still controversial among clinicians. In this study, we aimed to understand which definition is better in terms of establishing both early postnatal problems and growth. In this way, we compared early neonatal problems and infancy growth of term infants with birth weight (BW) < -2 SDS and with BW between 10th percentile (-1.28 SDS) and -2 SDS. Methods: A single center retrospective cohort study was conducted. Preterm infants, multiple gestations and newborns with any congenital anomalies were excluded from the study. Study group was defined as Group 1 (n = 37), infants BW < -2.00 SDS; Group 2 (n = 129), between -1.28 and -2.00 SDS; and Group 3 (n = 137), randomly selected newborns with optimal-for-gestational-age (BW between -0.67 and +0.67 SDS) as a control group. Results: The incidence of severe hypoglycemia was highest in Group 1 (%10.8) and Group 2 and 3 had similar rates of severe hypoglycemia (0.8 and 0.7%, respectively). The incidence of polycythemia was 5.4% in Group 1 and was significantly higher than Group 3 (0.0%) while it was 2.3% in Group 2. Short stature (length < -2 SDS) ratio at the age of 1 and 2 years were similar in each group. Overweight/obesity ratio at the age of 1 were 9.5, 20.8 and 16.7% in each group, respectively (p = 0.509). Conclusion: This study was planned as a pilot study to determine potential differences in the problems of hypoglycemia, polycythemia, and growth according to the differences in definition. Short term disturbances such as hypoglycemia and polycythemia are found to be higher in infants with a BW SDS below -2. From this point of view, of course, it will not be possible to change the routine applications immediately, however this study will be an initiative for discussions by making long-term studies.

Cranial MRI Abnormalities and Long-term Follow-up of the Lesions in 770 Girls With Central Precocious Puberty.

CONTEXT: Central precocious puberty (CPP) may arise from central nervous system (CNS) lesions in a few affected girls. Recently, the incidence of girls with CPP has increased mostly in 6-8 year olds, in whom the necessity of magnetic resonance imaging (MRI) is debated. OBJECTIVE: To investigate the frequency, long-term outcome and potential predictors of CNS lesions in a large cohort of girls with CPP. METHODS: A multicenter cohort of 770 Turkish girls with CPP who had systematic cranial MRI between 2005 and 2017. Age at puberty onset was <6 years in 116 and 6-8 years in 654. CNS lesions were followed until final decision(6.2 ± 3.1 years). Potential predictors of CNS lesions were evaluated by univariate analyses. RESULTS: A total of 104/770 (13.5%) girls had abnormal brain MRI. Of these, 2.8% were previously known CNS lesions, 3.8% had newly detected and causally related CNS lesions, 3.1 % were possibly, related and 3.8% were incidental. Only 2 (0.25%) neoplastic lesions (1 low grade glioma and 1 meningioma) were identified; neither required intervention over follow-up of 6 and 3.5 years respectively. Age at breast development <6 years (odds ratio [OR] 2.38; 95% CI 1.08-5.21) and the peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio >0.6 (OR 3.13; 95% CI 1.02-9.68) were significantly associated with CNS lesions. However, both patients with neoplastic lesions were >6 years old. CONCLUSION: Although age and LH/FSH ratio are significant predictors of CNS lesions, their predictive power is weak. Thus, systematic MRI seems to be the most efficient current approach to avoid missing an occult CNS lesion in girls with CPP, despite the low likelihood of finding a lesion requiring intervention.

Early Postnatal Metabolic Profile in Neonates With Different Birth Weight Status: A Pilot Study.

Introduction: Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated. Materials and Methods: A single-center retrospective cohort study was conducted. Three hundred and sixty-one newborn infants were enrolled into the study, and they were grouped according to their birth weight percentile as small for gestational age (SGA, n = 69), appropriate for gestational age (AGA, n = 168), and large for gestational age (LGA, n = 124) infants. In all infants, amino acid and carnitine/acylcarnitine profiles with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups. Results: LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine, and glycine (p < 0.05) when compared with AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH, and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p < 0.05). LGA infants had higher C3 and C5:1 levels and lower C18:2 and C16:1-OH levels (p < 0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine, and glycine levels (p < 0.05). Also, a positive correlation between ponderal index and C3, C5-DC, C14, and C14:1 and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, and C18:2 were shown. Conclusion: We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.

Molecular Diagnosis of Monogenic Diabetes and Their Clinical/Laboratory Features in Turkish Children

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey. Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study. Results: Seventy-seven (45.6%) female and 92 male cases with a mean age of 8.18±5.05 years at diagnosis were included. 52.7% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3±2.1%, 184.9±128.9 mg/dL, 9.4±22.9 IU/L, 1.36±1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2%), HNF1A-MODY in 31 (18.3%), and variants in ABCC8 in 6 (3.6%), KCNJ11 in 5 (3%), HNF4A in 2 (1.2%), and HNF1B in 2 (1.2%). Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50%), while GCK-MODY is the second most frequent (32%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20% of cases were diagnosed with HNF1A-MODY.

Hereditary vitamin D-resistant rickets: a report of four cases with two novel variants in the VDR gene and successful use of intermittent intravenous calcium via a peripheral route.

Background Hereditary vitamin D-resistant rickets (HVDRR) is caused by vitamin D receptor (VDR) defects. Patients with HVDRR do not respond to standard doses of calcitriol and oral calcium (Ca) treatment and need to be treated with intravenous Ca (IV-Ca) via a central route. However, central catheter-related complications can cause significant morbidity. Case presentation Four unrelated patients with HVDRR presenting with rickets and alopecia totalis were administered intermittent IV-Ca treatment (2-5 times/week) through a peripheral route. No complications such as infection, extravasation or arrhythmias were detected upon peripheral infusion. Peripheral 1-22 months' duration of IV-Ca normalized parathyroid hormone (PTH) and alkaline phosphatase (ALP) in all patients, after which, oral Ca of 200-400 mg/kg/day and calcitriol of 0.5 µg/kg/day were sufficient to maintain normal PTH levels. Molecular studies on the VDR gene showed a previously reported homozygous c.454C > T (p.Q152*) pathogenic variant in two patients. Two novel homozygous variants in the other two patients were detected: (1) c.756-2A > G, which affects the splice acceptor site, and (2) c.66dupG (p.I23Dfs*20) variant leading to a frameshift that results in a premature stop codon. Conclusions Peripheral IV-Ca treatment is an effective and practical alternative treatment mode that provides dramatic clinical benefit in patients with HVDRR.