ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 14 Issue : 2 Year : 2024

Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Volume: 14  Issue: 2 - 2022

Pages I - XI

2.Efficacy and Safety of Letrozole in the Management of Constitutional Delay in Growth and Puberty: A Systematic Review and Meta-analysis
Deep Dutta, Rajiv Singla, Vineet Surana, Meha Sharma
doi: 10.4274/jcrpe.galenos.2021.2021.0169  Pages 131 - 144
No meta-analysis is available which has analysed the role of letrozole in constitutional delay in growth and puberty (CDGP). Electronic databases were searched for randomized controlled trials (RCTs) involving children with CDGP receiving letrozole. Primary outcomes were changes in predicted adult height (PAH) and pubertal progression. Secondary outcomes were alterations in bone age (BA), hormonal markers of puberty, bone mineral density and side-effects. One hundred-thirty articles were reviewed, from which seven RCTs which fulfilled all criteria were analysed. Letrozole was superior to placebo [mean difference (MD) 4.63 cm (95% confidence interval (CI): 3.90-5.36); p<0.01; I2=0%] but not testosterone [MD: 2.21 cm (95% CI: -1.71-6.16); p=0.27; I2=98%] with regards to improvement in PAH after 12-months use. Letrozole was superior to both placebo [MD: 4.80 mL (95% CI: 0.57-9.03); p=0.03] and testosterone [MD: 3.36 mL (95% CI: 0.58-6.75); p=0.02; I2=0%] with regards to improvement in testicular volume after 12-months use. Letrozole tended to be superior to testosterone [MD: -0.84 years (95% CI: 2.83-8.18); p=0.06; I2=0%] with regards to slowing in BA progression after 12-months use. Serum luteinizing hormone, follicle stimulating hormone, testosterone and inhibin-B were significantly higher after 6-months letrozole use compared to active as well as passive controls. No increased occurrence of adverse events, including spinal deformities, were noted with letrozole. Letrozole is safe and effective for improving height and pubertal outcomes in CDGP, and is better than testosterone with regards to improvement in testicular volume and may be better at delaying bone-age progression.

3.A 4-hour Profile of 17-hydroxyprogesterone in Salt-wasting Congenital Adrenal Hyperplasia: Is the Serial Monitoring Strategy Worth the Effort?
Özge Besci, İbrahim Mert Erbaş, Tuncay Küme, Kübra Yüksek Acinikli, Ayhan Abacı, Ece Böber, Korcan Demir
doi: 10.4274/jcrpe.galenos.2021.2021-9-17  Pages 145 - 152
INTRODUCTION: Objective: Since there is no gold standard laboratory variable for adjustment of treatment in congenital adrenal hyperplasia (CAH), the aim was to assess the use of a 4-hour profile of serum 17-hydroxyprogesterone (17-OHP) to determine the most appropriate sample time and level of 17-OHP in predicting the metabolic control and evaluate the role of sex hormone-binding globulin (SHBG) in hyperandrogenemia.
METHODS: Methods: This study included children with salt-wasting CAH. Measurements for 17-OHP and cortisol were made from samples obtained before and 1, 2, and 4 hours after the morning dose of hydrocortisone. Patients were designated to have poor metabolic control when androstenedione levels according to age and sex-specific reference intervals were high and annual height standard deviation score (SDS) changes were ≥0.5.
RESULTS: Results: The study cohort was 16 children (9 girls) with a median age of 7-years old. Premedication 17-OHP levels were strongly correlated with 17-OHP levels 1, 2, and 4 hours after the morning dose (rs=0.929, p<0.01; rs=0.943, p<0.01; rs=0.835, p<0.01, respectively). 17-OHP profiles (0, 1, 2, 4 hours) of poor (n=6) and good (n=10) metabolically controlled cases were similar. Among the patients with poor metabolic control, two cases had 17-OHP levels <2 ng/mL at all times. The remaining patients with poor metabolic control had median 17-OHP levels above 104 ng/mL, 82 ng/mL, 14 ng/mL, and 4 ng/mL, for baseline and 1, 2, and 4 hours, respectively. Differences between the poor and well-controlled group were androstenedione levels with respect to upper limit of normal [1.8 (1.5) and 0.5 (1.5) ng/mL, respectively p=0.03], annual change in height SDS [0.7 (0.2) and -0.03 (0.8) SDS, respectively, p=0.001], and daily hydrocortisone doses [7 (6) and 16 (8) mg/m2/day, respectively, p=0.02]. Androstenedione and SHBG levels were negatively correlated in the pubertal children (rs=-0.7, p=0.04).
DISCUSSION AND CONCLUSION: Conclusion: We conclude that: (i) a 4-hour 17-OHP profile is not useful in predicting hyperandrogenemia; (ii) suppressed levels of 17-OHP do not always indicate overtreatment; (iii) reference intervals of 17-OHP for different time periods might be of importance; (iv) low hydrocortisone doses should be avoided; and (v) SHBG could be used in pubertal children as an indicator of hyperandrogenemia.

4.Mutations in AR or SRD5A2 Genes: Clinical Findings, Endocrine Pitfalls, and Genetic Features of Children with 46,XY DSD
Neşe Akcan, Oya Uyguner, Firdevs Baş, Umut Altunoğlu, Güven Toksoy, Birsen Karaman, Şahin Avcı, Zehra Yavaş Abalı, Şükran Poyrazoğlu, Agharza Aghayev, Volkan Karaman, Rüveyde Bundak, Seher Başaran, Feyza Darendeliler
doi: 10.4274/jcrpe.galenos.2022.2021-9-19  Pages 153 - 171
INTRODUCTION: 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: 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: 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.
DISCUSSION AND CONCLUSION: 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.

5.Revisiting the Annual Incidence of Type 1 Diabetes Mellitus in Children from the Southeastern Anatolian Region of Turkey: A Regional Report
Şervan Özalkak, Ruken Yıldırım, Selma Tunç, Edip Ünal, Funda Feryal Taş, Hüseyin Demirbilek, Mehmet Nuri Özbek
doi: 10.4274/jcrpe.galenos.2021.2021-10-7  Pages 172 - 178
INTRODUCTION: Objective: The incidence of type 1 diabetes mellitus (T1D) in children has an increasing trend globally, with a variable rate depending
on region and ethnicity. Our group first reported T1D incidence in Diyarbakır in 2011. The aim of this study was to evaluate the current
incidence rate of pediatric T1D in Diyarbakır, and compare the incidence, and clinical and presenting characteristics of more recent
cases with those reported in our first report.
METHODS: Methods: Hospital records of patients diagnosed with T1D in Diyarbakır city between 1st January 2020 and 31st December 2020 and
aged under 18 years old were retrieved, and their medical data was extracted. Demographic population data were obtained from
address-based census records of the Turkish Statistical Institution (TSI).
RESULTS: Results: Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female
ratio of 1.47. The mean age at diagnosis was 9.5±3.9 years (0.8-17.9). TSI data indicated a population count of 709,803 for the 0-18
years age group. Thus the T1D incidence was 8.03/105 in the 0-18 age group and was higher in the 0-14 age group at 9.14/105. The
cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The
frequency of presentation with diabetic ketoacidosis was 64.9%.
DISCUSSION AND CONCLUSION: Conclusion: The annual incidence of pediatric T1D in Diyarbakır city increased from 7.2/105 to 9.14/105 within the last decade. The rate
of annual increase was 2.7% in the 0-14 age group comparing this study with our earlier report, with a predominance in male subjects
and a shift of peak incidence from the 5-9 year age group in the first study to the 10-14 year age group in this one.

6.Low Complement C1q/TNF-related Protein-13 Levels are Associated with Childhood Obesity But not Binge Eating Disorder
İbrahim Mert Erbaş, Ahu Paketçi, Serkan Turan, Ali Rıza Şişman, Korcan Demir, Ece Böber, Ayhan Abacı
doi: 10.4274/jcrpe.galenos.2021.2021-11-1  Pages 179 - 187
INTRODUCTION: Objective: C1q/tumor necrosis factor-related proteins (CTRPs) are recently described members of the adipokine family. CTRP-13, a new member of this family, has been shown to increase insulin sensitivity and had an anorexigenic effect on food intake in experimental studies. The aim was to investigate serum CTRP-13 levels in children with obesity, and its relationship with other adipokines, metabolic parameters, or binge eating disorder (BED).
METHODS: Methods: A cross-sectional study was conducted with 105 pubertal children attending a single center. Clinical (metabolic syndrome, BED) and biochemical (glucose, insulin, lipids, leptin, adiponectin, CTRP-13 levels) parameters were assessed.
RESULTS: Results: Sixty children with obesity [24 males (40%); median age 14.7 (13.0-16.4) years] and 45 healthy controls [15 males (33.3%); median age 15.2 (14.1-16.5) years] were included. Serum adiponectin and CTRP-13 levels were significantly lower in children with obesity than controls (7.1 vs 20.1 μg/mL, p<0.001; 64.7 vs 103.8 ng/mL, p<0.001, respectively). CTRP-13 levels correlated negatively with body mass index (Spearman rho=-0.230, p=0.018) and positively with high-density lipoprotein-cholesterol levels (Spearman rho=0.218, p=0.026). There was no significant difference in serum CTRP-13 concentrations in terms of the presence of metabolic syndrome or BED.
DISCUSSION AND CONCLUSION: Conclusion: Childhood obesity seems to be causing dysregulation in adipokine production and function, including the down-regulation of CTRP-13. The positive correlation between CTRP-13 and HDL-C levels suggested a possible effect of this adipokine on lipid metabolism. Thus CTRP-13 may be a novel biomarker for dyslipidemia in childhood obesity.

7.How Vitamin D Levels of Children Changed During COVID-19 Pandemic: A Comparison of Pre-pandemic and Pandemic Periods
Güler Beyazgül, Özlem Bağ, İlkay Yurtseven, Fulya Coşkunol, Saynur Başer, Duygu Çiçek, Gül İrem Kanberoğlu, Filiz Çelik, Özlem Nalbantoğlu, Behzat Özkan
doi: 10.4274/jcrpe.galenos.2022.2021-10-6  Pages 188 - 195
INTRODUCTION: Objective: The synthesis of vitamin D is related to sun exposure, thus the restrictions during the Coronavirus disease-2019 (COVID-19) pandemic may have affected the levels of vitamin D in all age groups. The aim of this study was to evaluate vitamin D levels of healthy children and adolescents during the first year of the pandemic.
METHODS: Methods: The study group included healthy children and adolescents who were admitted for general check-ups and evaluated with 25(OH)D levels. Then, it was divided into two groups: Group 1 “pre-pandemic”, and Group 2 “pandemic”. Vitamin D levels were recorded from the hospital database and were compared according to age groups, gender, and the season, retrospectively.
RESULTS: Results: The study group [mean age=90.29±59.45 median age=79 interquartile range (IQR): 102 months, male/female: 1409/1624] included 3033 children and adolescents (Group 1/Group 2 n=1864/1169). Although the mean 25(OH)D levels among preschool children did not differ between groups, the vitamin D levels of school-aged children and adolescents were significantly lower in the pandemic period than in the pre-pandemic period [Group 1 median=16.50 (IQR: 10.5) vs Group 2 median=15.9 (IQR: 11.3) in 6-12 age group (p=0.026); Group 1 median=13.30 (IQR: 10.2) vs Group 2 median=11.20 (IQR: 9.7) in 12-18 age group (p=0.003)]. Moreover, the 25(OH)D levels of adolescents showed seasonal variance with lower levels in winter, and unexpectedly, in summer.
DISCUSSION AND CONCLUSION: Conclusion: Pandemic-related restrictions have caused significant decreases in vitamin D levels of school-aged children and adolescents. We suggest that children and adolescents should be given vitamin D supplementation in order to maintain sufficient levels of vitamin D during the pandemic.

8.The Role of American Thyroid Association Pediatric Thyroid Cancer Risk Stratification and BRAFV600E Mutation in Predicting the Response to Treatment in Papillary Thyroid Cancer Patients ≤18 Years Old
Yasemin Giles Şenyürek, Yalın İşcan, İsmail Cem Sormaz, Şükran Poyrazoğlu, Fatih Tunca
doi: 10.4274/jcrpe.galenos.2022.2021-10-4  Pages 196 - 206
INTRODUCTION: This study aimed to evaluate the role of risk stratification by the American Thyroid Association (ATA) pediatric thyroid cancer risk levels and BRAFV600E mutation to predict the response to treatment in papillary thyroid cancer (PTC) patients ≤18 years old.
METHODS: Clinical outcomes during a median period of 6 (2-21.8) years were assessed in 70 patients, according to ATA pediatric risk stratification, BRAFV600E mutation status, and dynamic risk stratification (DRS) at final follow-up.
RESULTS: Of 70 patients, 44 (63%), 14 (20%), and 12 (17%) were classified initially as low-, intermediate-, and high-risk, respectively. BRAFV600E mutation analysis data was available in 55 (78.6%) patients, of whom 18 (32.7%) had the BRAFV600E mutation. According to the final DRS, 61 (87%), two (3%), six (9%), and one (1%) patients were classified as an excellent, incomplete biochemical, incomplete structural, and indeterminate response, respectively. All ATA low-risk patients showed excellent response to treatment, whereas the rate of excellent response was 65.4% in intermediate- and high-risk levels (p<0.001). The rates of excellent response in BRAFV600E positive and negative patients were 83% and 92%, respectively (p=0.339). The rate of locoregional recurrence was significantly higher in BRAFV600E positive vs negative patients (33.3% vs 2.7% respectively, p=0.001).
DISCUSSION AND CONCLUSION: ATA pediatric risk stratification is effective in predicting response to treatment in PTC patients ≤18 years old. The presence of BRAFV600E mutation was highly predictive for recurrence but had no significant impact on the rate of excellent response to treatment at final follow-up.

9.Comparison of National Growth Standards for Turkish Infants and Children with World Health Organization Growth Standards
Rüveyde Bundak, Zehra Yavaş Abalı, Andrzej Furman, Feyza Darendeliler, Gülbin Gökçay, Firdevs Baş, Hülya Günöz, Olcay Neyzi
doi: 10.4274/jcrpe.galenos.2022.2021-9-10  Pages 207 - 215
INTRODUCTION: 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.
DISCUSSION AND 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.

10.The Impact of the CEDD-NET on the Evaluation of Rare Disorders: A Multicenter Scientific Research Platform in the Field of Pediatric Endocrinology
Samim Özen, Aysun Ata, Feyza Darendeliler
doi: 10.4274/jcrpe.galenos.2022.2021-11-16  Pages 216 - 220
INTRODUCTION: The database http: // (CEDD-NET) has been operating since 2013 in Turkey. All pediatric endocrinologists can propose projects to this network. The aim of our study was to determine the impact of CEDD-NET on the transformation of multicenter studies into scientific publications and assess the academic characteristics of the studies that have been transcribed into publication.
METHODS: All the studies that were opened to patient admission on the website between August 26, 2013 and March 1, 2021 were reviewed.
RESULTS: A total of 30 studies were accepted and opened for data entry. The median data collection period was 12 (1.5-24) months, while the median number of researchers participated was 23 (3-180), the median number of cases was 120 (26-192). The average cost was $2113 (1370-3118). Out of 30 studies, data entry was completed for 27. Sixteen publications were produced from 14 studies, 13 ot them have not published yet. The median time from the end of data entry to publication of the study was 686 (168-1608) days. While the median impact factor of the journals in which the studies were published was 1.803 (1.278-5.399), the median number of citations was 6.5 (0-49), and cited by 99 times in Web of Science indexed journals in total.
DISCUSSION AND CONCLUSION: CEDD-NET appears to be productive and effective as all the publications are of high quality that have been published in the Q1-Q2 categories. This study demonstrated the benefits and necessity of establishing nationwide databases, even covering more than one country, in specialized branches, such as pediatric endocrinology where rare diseases are of concern.

11.A Novel Mutation in the Thyroglobulin Gene Resulting in Neonatal Goiter and Congenital Hypothyroidism in an Eritrean Infant
Eve Stern, Nadia Schoenmakers, Adeline K. Nicholas, Eran Kassif, Orit Pinhas Hamiel, Yonatan Yeshayahu
doi: 10.4274/jcrpe.galenos.2021.2020.0278  Pages 221 - 226
Congenital hypothyroidism (CH) due to dyshormonogenesis may occur due to mutations in any of the key genes involved in thyroid hormone biosynthesis (TG, TPO, DUOX2, DUOXA2, SLC5A5, IYD, SLC26A4 and SLC26A7). Mutations in the thyroglobulin gene (TG) are frequently associated with goiter, which may present fetally or neonatally, although a spectrum of phenotypes is reported. We present the case of a woman of Eritrean origin who presented in the third trimester of pregnancy in the early stages of labor. Ultrasound at presentation revealed a fetal neck swelling consistent with a goiter. Following delivery by Caesarian section with minimal respiratory support, the infant was found to be hypothyroid with undetectable serum levels of thyroglobulin. Sequencing of the TG revealed a homozygous donor splice site pathogenic variant (c.5686+1delG) not previously described in the literature. Levothyroxine treatment resulted in normal growth and psychomotor development. Goitrous CH with inappropriately low thyroglobulin has previously been reported in patients harbouring homozygous single nucleotide substitutions at the same TG donor splice site, which result in exon skipping and retention of malformed thyroglobulin by the endoplasmic reticulum. We conclude that the TG c.5686+1delG pathogenic variant is the likely basis for our patient’s fetal goiter and CH, and that the clinical phenotype associated with TG c.5686+1delG is comparable to that seen with single nucleotide substitutions at the same site.

12.TRMT10A Mutation in a Child with Diabetes, Short Stature, Microcephaly and Hypoplastic Kidneys
Eve Stern, Asaf Vivante, Ortal Barel, Yael Levy-Shraga
doi: 10.4274/jcrpe.galenos.2020.2020.0265  Pages 227 - 232
A new syndrome of diabetes, short stature, microcephaly and intellectual disability has been described in association with mutations in the tRNA methyltransferase 10 homologue A (TRMT10A) gene. We report a patient who presented with fasting hyperglycemia, a raised hemoglobin A1c and positive islet cell autoantibodies. Additional clinical features included intellectual disability, hypoplastic kidneys and short stature. In view of the syndromic features coexistant with diabetes, genetic evaluation was carried out, revealing a homozygous mutation in the TRMT10A gene (c.616G>A, p.G206R). The case highlights the importance of genetic evaluation of patients with diabetes with atypical features that can further progress our understanding of the pathophysiology of the rarer subtypes of diabetes.

13.46,XY Sex Development Defect due to a Novel Homozygous (Splice Site) c.673_1G>C Variation in the HSD17B3 Gene: Case Report
Nurdan Çiftci, Leman Kayaş, Emine Çamtosun, Ayşehan Akıncı
doi: 10.4274/jcrpe.galenos.2020.2020.0249  Pages 233 - 238
The enzyme 17-β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) catalyzes the biosynthesis of testosterone (T) from Δ4-androstenedione, and plays an important role in the final steps of androgen synthesis. 17β-HSD3 deficiency originates from mutations in the HSD17B gene, causing an autosomal recessive 46,XY sex developmental disorder (DSD). Patients with 46,XY karyotype can exhibit a wide phenotypic spectrum, varying from complete external female genitalia to male genitalia with hypospadias. Here we report a case of 17β-HSD3 deficiency diagnosed in the infantile period who was later found to have a novel HSD17B3 gene variation. The 14-month old patient, who exhibited a female phenotype, presented with a bilateral lump in the inguinal area. Imaging revealed bilateral testicular gonads in the inguinal area. Hormonal evaluation showed low levels of basal and stimulated serum T, a high level of androstenedione (A), and a low T/A ratio. Chromosomal analysis showed 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a c.673_1G>C homozygous class 2 (splice site) variation in intron 9. The consanguineous parents were sequenced, and both were heterozygous for the same mutation. This variation has not been previously reported in the literature. In conclusion, a 46,XY DSD should be considered in patients with a female phenotype who exhibit gonad(s) in the inguinal area at an early age. Furthermore, in patients with insufficient T synthesis and high levels of androstenedione, 17β-HSD3 should be considered, and molecular analysis should be done for a definitive diagnosis and subsequent genetic counseling.

14.The Successful Treatment of Deep Soft-tissue Calcifications with Topical Sodium Thiosulphate and Acetazolamide in a Boy with Hyperphosphatemic Familial Tumoral Calcinosis due to a Novel Mutation in FGF23
Hakan Döneray, Ayşe Özden, Kadri Gürbüz
doi: 10.4274/jcrpe.galenos.2021.2020.0269  Pages 239 - 243
Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder. Topical sodium thiosulfate (STS) and acetazolamide can be a safe and effective treatment for patients who do not respond to conventional therapy for ectopic calcifications. We report the successful treatment of deep soft-tissue calcifications with topical STS and acetazolamide in a boy diagnosed with HFTC due to a novel homozygous mutation of FGF23.

15.A Novel SCNN1A Variation in a Patient with Autosomal-recessive Pseudohypoaldosteronism Type 1
Mohammed Ayed Huneif, Ziyad Hamad Alhazmy, Anas M. Shoomi, Mohammed A. Alghofely, Humariya Heena, Aziza M. Mushiba, Abdulhamid Alsaheel
doi: 10.4274/jcrpe.galenos.2021.2020.0175  Pages 244 - 250
Pseudohypoaldosteronism type 1 (PHA1) is an autosomal-recessive disorder characterized by defective regulation of body sodium (Na) levels. The abnormality results from mutations in the genes encoding subunits of the epithelial Na channel. Patients with PHA1 present in infancy as being in adrenal crisis. A 41-day-old female who presented with recurrent adrenal crisis did not adequately respond to hydrocortisone and required mineralocorticoid therapy. The patient’s demographic data and clinical features were recorded. Blood samples were collected and tested for endocrine and metabolic characteristics and for use in genetic studies. Bidirectional Sanger sequencing of SCNN1A was conducted. The entire coding region of 12 exons and 20 bp of flanking intron were sequenced. Genetic analyses revealed a new mutation - c.729_730delAG (p.Val245Glyfs*65) - in SCNN1A exon four. Adrenal crisis during the neonatal period highlights the importance of early screening for PHA1. Genetic testing could help to anticipate the prognosis, severity, onset of the disease, and the mode of inheritance, especially given its extensive phenotype.

16.Bilateral Ovarian Germ Cell Tumor in a 46,XX Female with Nijmegen Breakage Syndrome and Hypergonadotropic Hypogonadism
Malgorzata A. Krawczyk, Malgorzata Styczewska, Dorota Birkholz-Walerzak, Mariola Iliszko, Beata S. Lipska-Zietkiewicz, Wojciech Kosiak, Ninela Irga-Jaworska, Ewa Izycka-Swieszewska, Ewa Bien
doi: 10.4274/jcrpe.galenos.2021.2021.0151  Pages 251 - 257
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, affecting mainly patients of Slavic origin. It is caused by a defect in the NBN gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating. Nibrin is also involved in gonadal development and its disfunction in females with NBS frequently results in a pure gonadal dysgenesis (PGD) causing hypergonadotropic hypogonadism. However, only a few ovarian tumors in NBS patients have been reported to date. We describe the first case of a girl with NBS with PGD, who developed metachronous bilateral ovarian germ cell tumors (dysgerminoma and gonadoblastoma). Pathogenesis of PGD, neoplastic transformation and therapeutic approach in females with NBS are discussed.

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