Person: BEREKET, ABDULLAH
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
BEREKET
First Name
ABDULLAH
Name
52 results
Search Results
Now showing 1 - 10 of 52
Publication Metadata only Clinical Significance of Hypophosphatasemia in Children(SPRINGER, 2020) BEREKET, ABDULLAH; Bayramli, Rana; Cevlik, Tulay; Guran, Tulay; Atay, Zeynep; Bas, Serpil; Haklar, Goncagul; Bereket, Abdullah; Turan, SerapLow serum alkaline phosphatase (sALP)-hypophosphatasemia-is a characteristic of hypophosphatasia (HPP), but related to several clinical conditions. Here, we evaluated the frequency, persistency and the etiology of hypophosphatasemia in children. In retrospective analyses of sALP measurements from children, evaluated according to in-house constructed age- and sex-specific reference ranges, patients with no normal sALP measurement (Unresolved hypophosphatasemia) were invited for reanalysis. Prospectively, ALP substrates, pyridoxal-5-phosphate (PLP), and phosphoethanolamine (PEA) were measured in patients with persistent hypophosphatasemia. Radiographs and ALPL gene sequencing for HPP were performed to the cases with elevated PEA and/or PLP. From 130,340 sALP measurements of 93,162 patients, hypophosphatasemia was detected in 1404 samples from 867 patients (0.9%). Among them, 745 had at least one normal sALP values in laboratory records, grouped as transient hypophosphatasemia. 75 out of 122 patients with unresolved hypophosphatasemia could be reanalyzed for sALP, of whom PLP and PEA measurements were required in 37 due to persistent hypophosphatasemia. Both PEA and PLP were elevated in 4 patients, and ALPL gene analysis showed heterozygous mutations in 3 patients and homozygous in 1 patient. Elevated PEA with normal PLP were detected in 3 patients, and one had a heterozygous ALPL mutation. Anemia was the most common diagnosis, and upper respiratory tract infections and chronic diseases were more common in transient and unresolved hypophosphatasemia, respectively. In conclusion, reflected persistent hypophosphatasemia frequency was 1/1552 (0.06%) in this large pediatric cohort and, ALPL gene mutations were detected in 13.5% (5/37) of the studied cases. Although biochemical hypophosphatasemia is not uncommon, clinically significant HPP is rare.Publication Open Access A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age(SPRINGER, 2020-07) DAĞÇINAR, ADNAN; Eltan, Mehmet; Alavanda, Ceren; Yavas Abali, Zehra; Ergenekon, Pinar; Yalindag Ozturk, Nilufer; Sakar, Mustafa; Dagcinar, Adnan; Kirkgoz, Tarik; Kaygusuz, Sare Betul; Gokdemir, Yasemin; Elcioglu, Huriye Nursel; Guran, Tulay; Bereket, Abdullah; Ata, Pinar; Turan, SerapRaine Syndrome (RS) is caused by biallelic loss-of-function mutations in FAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ears, triangular mouth, and corneal opacification were detected on physical examination. Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually decreased by the age of 5 months with subperiosteal undermineralized bone formation and medullary space of long bone could be distinguishable with bone-within-a-bone appearance. At 9 months of age, hand X-ray revealed cupping of the ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial computed tomography scan showed bilateral periventricular calcification and hydrocephalus in progress. The clinical, laboratory, and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20C gene (a known pathogenic mutation, c.1645C > T, p.Arg549Trp; and a novel c.863 + 5 G > C variant). The patient died due to respiratory failure at 17 months of age. This case allowed us to demonstrate natural progression of skeletal features in RS. Furthermore, we have described a novel FAM20C variant causing RS. Previous literature on RS is also reviewed.Publication Open Access Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features(SPRINGER, 2021-11-11) BEREKET, ABDULLAH; Eltan, Mehmet; Abali, Zehra Yavas; Turkyilmaz, Ayberk; Gokce, Ibrahim; Abali, Saygin; Alavanda, Ceren; Arman, Ahmet; Kirkgoz, Tarik; Guran, Tulay; Hatun, Sukru; Bereket, Abdullah; Turan, SerapBiallelic 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.Publication Metadata only Revisiting Classical 3 beta-hydroxysteroid Dehydrogenase 2 Deficiency: Lessons from 31 Pediatric Cases(ENDOCRINE SOC, 2020) BEREKET, ABDULLAH; Guran, Tulay; Kara, Cengiz; Yildiz, Melek; Bitkin, Eda C.; Haklar, Goncagul; Lin, Jen-Chieh; Keskin, Mehmet; Barnard, Lise; Anik, Ahmet; Catli, Gonul; Guven, Ayla; Kirel, Birgul; Tutunculer, Filiz; Onal, Hasan; Turan, Serap; Akcay, Teoman; Atay, Zeynep; Yilmaz, Gulay C.; Mamadova, Jamala; Akbarzade, Azad; Sirikci, Onder; Storbeck, Karl-Heinz; Baris, Tugba; Chung, Bon-Chu; Bereket, AbdullahContext: The clinical effects of classical 3 beta-hydroxysteroid dehydrogenase 2 (3 beta HSD2) deficiency are insufficiently defined due to a limited number of published cases. Objective: To evaluate an integrated steroid metabolome and the short- and long-term clinical features of 3 beta HSD2 deficiency. Design: Multicenter, cross-sectional study. Setting: Nine tertiary pediatric endocrinology clinics across Turkey. Patients: Children with clinical diagnosis of 3 beta HSD2 deficiency. Main Outcome Measures: Clinical manifestations, genotype-phenotype-metabolomic relations. A structured questionnaire was used to evaluate the data of patients with clinical 3 beta HSD2 deficiency. Genetic analysis of HSD3B2 was performed using Sanger sequencing. Novel HSD3B2 mutations were studied in vitro. Nineteen plasma adrenal steroids were measured using LC-MS/MS. Results: Eleven homozygous HSD3B2 mutations (6 novel) were identified in 31 children (19 male/12 female; mean age: 6.6 +/- 5.1 yrs). The patients with homozygous pathogenic HSD3B2 missense variants of > 5% of wild type 3 beta HSD2 activity in vitro had a non-salt-losing clinical phenotype. Ambiguous genitalia was an invariable feature of all genetic males, whereas only 1 of 12 female patients presented with virilized genitalia. Premature pubarche was observed in 78% of patients. In adolescence, menstrual irregularities and polycystic ovaries in females and adrenal rest tumors and gonadal failure in males were observed. Conclusions: Genetically-documented 3 beta HSD2 deficiency includes salt-losing and non-salt-losing clinical phenotypes. Spared mineralocorticoid function and unvirilized genitalia in females may lead to misdiagnosis and underestimation of the frequency of 3 beta HSD2 deficiency. High baseline 17OHPreg to cortisol ratio and low 11-oxyandrogen concentrations by LC-MS/MS unequivocally identifies patients with 3 beta HSD2 deficiency.Publication Open Access Homozygosity for a novel INHA mutation in two male siblings with hypospadias, primary hypogonadism, and high-normal testicular volume(2022-03-23) ŞAHİN, BAHADIR; DEMİRCİOĞLU, SERAP; BEREKET, ABDULLAH; GÜRAN, TÜLAY; Arslan Ateş E., Eltan M., Sahin B., Gurpinar Tosun B., Seven Menevse T., Geckinli B. B., Greenfield A., Turan S., Bereket A., Güran T.Background: The human INHA gene encodes the inhibin subunit alpha protein, which is common to both inhibin A and B. The functional importance of inhibins in male sex development, sexual function, and reproduction remain largely unknown. Objective: We report for the first time two male siblings with homozygous INHA mutations. Methods: The medical files were examined for clinical, biochemical, and imaging data. Genetic analysis was performed using next-generation and Sanger sequencing methods. Results: Two brothers complained of gynecomastia, testicular pain, and had a history of hypospadias. Biochemistry revealed low serum testosterone, high gonadotropin and anti-Mullerian hormone, and very low/undetectable inhibin concentrations, where available. Both patients had azoospermia in the spermiogram. We have identified a homozygous 2 bp deletion (c.208_209delAG, R70Gfs*3) variant, which leads to a truncated INHA protein in both patients, and confirmed heterozygosity in the parents. The external genital development, pubertal onset and progression, reproductive functions, serum gonadotropins, and sex hormones of mother and father, who were heterozygous carriers of the identified mutation, were normal. Conclusion: Homozygosity for INHA mutations causes decreased prenatal and postnatal testosterone production and infertility in males, while the heterozygous female and male carriers of INHA mutations do not have any abnormality in sex development and reproduction.Publication Metadata only Persistent Mullerian Duct Syndrome: A Rare But Important Etiology of Inguinal Hernia and Cryptorchidism(KARGER, 2020) BEREKET, ABDULLAH; Bugrul, Fuat; Abali, Zehra Yavas; Kirkgoz, Tarik; Cerit, Kivilcim K.; Canmemis, Arzu; Turan, Serap; Tugtepe, Halil; Picard, Jean-Yves; Bereket, Abdullah; Guran, TulayHomozygous loss of function mutations in genes encoding anti-Mullerian hormone (AMH) or its receptor (AMHRII) lead to persistent Mullerian duct syndrome (PMDS). PMDS is characterized by the presence of a uterus, fallopian tubes, cervix, and upper vagina in fully virilised 46,XY males. Both surgical management and long-term follow-up of these patients are challenging. Four cases with PMDS presented with cryptorchidism and inguinal hernia, and laparoscopic inguinal exploration revealed Mullerian remnants. Three of the patients had homozygous mutations in the AMH gene, one with a novel c.1673G>A (p.Gly558Asp) mutation, and one patient had an AMHRII mutation. All patients underwent a single-stage laparotomy in which the fundus of the uterus was split along the midline to release testes and to avoid damaging the vas deferens or the deferential artery. Biopsy of Mullerian remnants did not reveal any malignancy. The cases presented here expand the clinical and molecular presentation of PMDS. Cryptorchidism and inguinal hernia in the presence of Mullerian structures in an appropriately virilised 46,XY individual should suggest PMDS. Long-term reproductive and endocrinological surveillance is necessary.Publication Metadata only Does Genotype-Phenotype Correlation Exist in Vitamin D-Dependent Rickets Type IA: Report of 13 New Cases and Review of the Literature(SPRINGER, 2021) BEREKET, ABDULLAH; Kaygusuz, Sare Betul; Alavanda, Ceren; Kirkgoz, Tarik; Eltan, Mehmet; Yavas Abali, Zehra; Helvacioglu, Didem; Guran, Tulay; Ata, Pinar; Bereket, Abdullah; Turan, SerapVitamin D-dependent rickets type IA (VDDR-IA) is caused by biallelic mutations in CYP27B1. Data regarding genotype-phenotype correlation in VDDR-IA are scarce. Here, we aimed to investigate clinical/genotypic features and long-term follow-up of 13 new cases with VDDR-IA and genotype-phenotype correlation of reported cases in the literature. Thirteen patients with VDDR-IA were evaluated. Eight patients had reached their final height at the time of the study and, for whom, long-term outcome data were analyzed. Further, all VDDR-IA patients in the literature (n:183) were analyzed and clinical-genetic features were recorded. The median age of diagnosis was 2.55 +/- 1.13 (1.0-12) years. Initial diagnoses before referral to our clinic were nutritional rickets (n:7), hypophosphatemic rickets (n:2), and pseudohypoparathyroidism (n:1). All had biochemical evidence suggestive of VDDR-IA; except one with elevated 1,25(OH)(2)D3 and another with hyperphosphatemia, in whom pseudohypoparathyroidism was excluded with molecular tests. Combined analyses of our cohort and other series in the literature demonstrated that three most common CYP27B1 mutations are p.F443Pfs*24, c.195 + 2T > G, and p.V88Wfs*71. In Turkish population, p.K192E mutation along with the former two is the most common mutations. Comparison of clinical features demonstrated that c.195 + 2T > G mutation causes the most severe and p.K192E mutation causes the least severe phenotype with respect to age and height at presentation and calcitriol requirement. We found a clear genotype-phenotype correlation in VDDR-IA, notably CYP27B1 intronic c.195 + 2T > G mutation causes a more severe phenotype with lower height SDS at presentation and, higher calcitriol requirement, while less severe phenotype occurs in p.K192E mutation.Publication Metadata only Restoration of Height after 11 Years of Letrozole Treatment in 11 beta-Hydroxylase Deficiency(KARGER, 2020) BEREKET, ABDULLAH; Atay, Zeynep; Turan, Serap; Bugdayci, Onur; Guran, Tulay; Bereket, Abdullah11 beta-hydroxylase deficiency (11 beta-OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Males with 11 beta-OHD CAH are often diagnosed late with a significantly advanced bone age leading to a poor height prognosis due to early closure of epiphysis. Delaying epiphyseal fusion by treatment of aromatase inhibitors (AIs) might be a useful strategy in patients with very advanced bone ages. However, there are limited data regarding the effect on final height and long-term safety of this approach. We report our experience with 11 years of letrozole treatment and 17 years of follow-up in a boy with 11 beta-OHD. He presented at 2 years and 11 months of age with a bone age of 13 years (predicted adult height, PAH, 129.5 cm). Letrozole was added after 1 year of glucocorticoid treatment due to no improvement in height prognosis (130 cm), and continued until the age of 14 years and 11 months. He also received GnRH analog treatment at 10 years and 3 months of age for 2.5 years due to central activation of puberty. He reached a final height of 165.2 cm (35.2 cm above his PAH). This long-term treatment with letrozole was associated with changes in vertebral morphology such as vertebral body end-plate changes, Schmorl nodes, and mild protrusions in the intervertebral discs. Testicular volumes, gonadotropins, testosterone, and anti-Mullerian hormone were normal at age 20 years. A spermiogram showed a normal count but impaired sperm motility and morphology. This unique case represents the longest duration of AI treatment reported in CAH and the first case in which letrozole was started before puberty with the final height reported. We conclude that AIs may restore height in selected patients with CAH with very advanced bone age and severely compromised height prognosis.Publication Open Access A novel deletion involving the first GNAS exon encoding Gsα causes PHP1A without methylation changes at exon A/B(2022-04-01) BEREKET, ABDULLAH; DEMİRCİOĞLU, SERAP; GÜRAN, TÜLAY; Campbell D., Reyes M., Kaygusuz S. B., Abalı S., Güran T., Bereket A., Kagami M., Turan S., Jüppner H.© 2022Individuals 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.Publication Metadata only Change of menarcheal age in schoolgirls living in Istanbul over the last 12 years(2022-09-01) GÜRAN, TÜLAY; GÜRPINAR TOSUN, BUŞRA; HALİLOĞLU, BELMA; DEMİRCİOĞLU, SERAP; HIDIROĞLU, SEYHAN; BEREKET, ABDULLAH; GÜRAN T., Alir F., Arslan Y. T. , Molla G., Sahin B., Sayar M. E. , Atay Z., Helvacioglu D., GÜRPINAR TOSUN B., HALİLOĞLU B., et al.