bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU149 A Novel Frameshift Mutation (p.H485fs) Of The Ldl Receptor Gene
Authors: Chang Seong Hwan , Yang Eun Mi , Kim Chan Jong 
Published: October 2023

Abstract
Disclosure: S. Chang: None. E. Yang: None. C. Kim: None.
Familial hypercholesterolemia (FH) is characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) that leads to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age and increases the risk of premature cardiovascular events such as angina and myocardial infarction. It is an autosomal dominant inherited disease due to mutations in either the low-density lipoprotein receptor (LDL-R), the apolipoprotein B or the proprotein convertase subtilisin/kexin type 9 genes. In this study, we report a novel mutation in LDL receptor gene in a Korean family. A 10 year-old boy was referred to our hospital for hypercholesterolemia (530 mg/dl). On family history, His father and uncle have been treated for hypercholesterolemia and his grandfather died of coronary artery disease. Because of persisted hypercholesterolemia despite statin treatment for 18 months and his family history, we performed LDL-R gene study using polymerase chain reaction (PCR) sequencing. Direct sequencing of the 18 exons and exon-intron boundaries of LDL-R gene revealed deletions of C and A of exon 10 (c.1455_1456del). Study showed a novel heterozygous frameshift-deletion mutation (p.His485Glnfs*50) (p.H485fs). We performed PCR sequencing to detect same mutation on his family. Father and two siblings of the patient have same mutation (p.His485Glnfs*50) (p.H485fs) on study. Now we report a novel frameshift mutation (p.H485fs) located in exon 10 of LDL receptor gene that causes familial hypercholesterolemia in a Korean family.
Presentation: Thursday, June 15, 2023
THU150 The Association Between Glycated Albumin And HbA1c In Pediatric Acute Leukemia Patients
Authors: Sim Soo Yeun , Ahn Moon Bae , Suh Byung-Kyu 
Published: October 2023

Abstract
Disclosure: S. Sim: None. M. Ahn: None. B. Suh: None.
Introduction: Traditionally, HbA1c has been used as a preferred glycemic index in diabetes patients. However, as many acute leukemia patients often present with anemia and/or pancytopenia, HbA1c may not accurately represent blood glucose level in this group. Glycated albumin represents the average level of blood glucose in recent 2-3 weeks, independent of red blood cell life. In this study, we aim to evaluate the usefulness of glycated albumin as glycemic monitoring index in pediatric patients diagnosed with acute leukemia. Methods: We performed retrospective analysis of a total of 206 pediatric patients from The Seoul St. Mary’s hospital, Catholic university of Korea. Medical records of 25 patients diagnosed with type 2 DM and 66 patients with acute leukemia were investigated for serum glycated albumin, HbA1c, fasting blood glucose level, and demographic data such as sex, age, height, weight and BMI z-scores. 115 children and adolescents who visited our outpatient center for routine child health examination were enrolled as the control group. Results: The median serum glycated albumin levels were 12.4%, 19.1% for acute leukemia and T2DM patients. HbA1c and fasting blood glucose levels, 5.3% and 7.6%, 92mg/dl and 129mg/dl respectively, also differed in the two groups. All glycated albumin, HbA1c and fasting blood glucose level did not appear different in between the control and acute leukemia group. In type 2 DM patients, glycated albumin and HbA1c showed positive correlations (r=0.926, p&lt;0.01). Fasting blood glucose level was also positively correlated to glycated albumin (r=0.821, p&lt;0.001) and HbA1c (r=0.773, p&lt;0.001). While glycated albumin did not appear related to HbA1c in the normal control group (r=-0.02, p=0.824), patients with acute leukemia also revealed a positive correlation between glycated albumin and HbA1c (r=0.253, p=0.04). Glycated albumin was negatively related to BMI z-scores in the control group (r=0.554, p&lt;0.001); however, the level showed no correlation to BMI z-scores in acute leukemia group and in T2DM patients (r=-0.133, p=0.286 and r=-0.292, p=0.156). HbA1c level was positively related to BMI z-scores in the control group (r=0.241, p=0.01) and showed no relations in the other two groups. Regression analysis found glycated albumin to be positively correlated to HbA1c both in acute leukemia pediatric patients and T2DM patients even when adjusted for age, sex and BMI z-score (p=0.039, p=0.007). Conclusion: In acute leukemia patients, glycated albumin may be a complementary parameter of glycemic status as in diabetic patients.
Presentation: Thursday, June 15, 2023
THU151 Undiagnosed MODY In Case Of Morbid Obesity
Authors: Abdulkader Ahmad , Ten Svetlana B 
Published: October 2023

Abstract
Disclosure: A. Abdulkader: None. S.B. Ten: None.
MODY is suspected in nonobese subjects with hyperglycemia, negative islet cell antibodies, and a family history of diabetes. Children with morbid obesity and diabetes can still have MODY and require different treatment. Case report The patient was born after a pregnancy complicated with gestational diabetes, treated with insulin, BW 9 1/2 lbs. He had early onset obesity from 3 yrs. of age. At 8 yrs., he developed impaired glucose tolerance, elevated triglycerides, low HDL, and fatty liver. He developed diabetes at 11 yrs. and was treated with Insulin, but treatment was not effective, Hb A1c was 11.4%, and BMI was 51.8 kg/m2. At 12 yrs., he was diagnosed with MODY on the base of normal C-peptide, negative islet cell AB, strong family history of diabetes: mother, uncle and MGM had diabetes. Insulin was discontinued. Glyburide and Metformin were started that improved his glucose level significantly. Hb A1c improved to 6.2%. Diet was changed, physical exercises were added, and he lost 25 lbs., BMI improved to 44.8 kg/m2. His mother, 46 yrs. old, was diagnosed with diabetes type 1 at 18 yrs. and treated with Insulin. She also had morbid obesity with BMI 48 kg/m2. She developed diabetic neuropathy, nephropathy, and had amputation of the left leg below the knee, eGFR 44 mL/min/1.73m2, Hb A1c 10.5%. She was diagnosed with MODY on the base of normal C-peptide 3.21 ng/mL, negative islet cell AB, family history of diabetes: her mother, brother, son have diabetes. Glyburide and pioglitazone were started, Insulin total daily dose was decreased from 90 units to 15 units a day. Her Hb A1c improved to 6 %, insulin was discontinued. She underwent Roux-en-Y Gastric Bypass surgery, lost 30 lbs. BMI improved to 42 kg/m2, Hb A1c became 5.3%. Her current glucose level is normal on Glyburide 2.5 mg and pioglitazone 7.5 mg daily. Results: Patient and his mother had heterozygous gene polymorphism in GLIS3, c.951G&gt;T (p.Glu317Asp). This sequence replaces glutamic acid with aspartic acid at codon 317 of the GLIS3 protein (p.Glu317Asp). GLIS3 is a variant of MODY and is a transcriptional factor in beta cell differentiation and insulin production. Patient and mother had pathogenic heterozygous variant of KSR2 gene, c.1622del, resulting in a frameshift and premature protein termination (p.Lys541Serfs*27). Pathogenic variants in KSR2 are associated with obesity and insulin resistance. Patient was also heterozygous in the NTRK2 gene for a sequence variant c.500C&gt;A, which is predicted to result in the amino acid substitution p.Ser167Tyr, also associated with obesity. Conclusion Genetic analysis of MODY is necessary even in cases of diabetes with morbid obesity, negative islet cell AB, positive family history of diabetes. Diagnosis of MODY helps provide individualized treatment and avoid complications secondary to unnecessary treatment with insulin.
Presentation: Thursday, June 15, 2023
THU183 The Genotype-phenotype Correlation In Human 5α-reductase Type 2 Deficiency: Classified And Analysed From A SRD5A2 Structural Perspective
Authors: Kwon Ahreum , Kim Sujin , Choi Youngha , Choi Hansaem , Kim Ho-Seong 
Published: October 2023

Abstract
Disclosure: A. Kwon: None. S. Kim: None. Y. Choi: None. H. Choi: None. H. Kim: None.
The phenotype of 5α-Reductase type 2 deficiency (5αRD2) by SRD5A2 gene mutation varies, and even though there have been many attempts, the genotype-phenotype correlation has not yet still been evaluated. Recently, the crystal structure of 5α-reductase type 2 isozyme (SRD5A2) was discovered. Therefore, the present study retrospectively evaluated the genotype-phenotype correlation from a structural perspective in 19 Korean patients with 5αRD2. Additionally, variants were classified according to structural categories relative to phenotypic severity based on previously published data. The p.R227Q variant, which belongs to the NADPH binding residue mutation category, exhibited a more masculine phenotype (higher external masculinisation score) than other variants. Furthermore, compound heterozygous mutations with p.R227Q, mitigated phenotypic severity. Similarly, other mutations in this category showed mild to moderate phenotypes. Conversely, those variants categorised as structure destabilising and small to bulky residue mutations showed moderate to severe phenotypes, and the variants categorised as catalytic site and helix breaking mutations exhibited severe phenotypes. Therefore, the SRD5A2 structural approach suggested that a genotype-phenotype correlation does exist in 5αRD2. We can also conclude that the categorisation of SRD5A2 gene variants facilitates prediction of the severity of 5αRD2, its prognosis, and the management and genetic counselling of patients affected by it.
Presentation: Thursday, June 15, 2023
THU196 Insulin-like Growth Factor-1 As A Screening Tool For Central Precocious Puberty
Authors: Chung Lindsey Yoojin , Im Minji 
Published: October 2023

Abstract
Disclosure: L. Chung: None. M. Im: None.
Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard test for diagnosing central precocious puberty (CPP), which needs time and effort to perform. Recently, many studies confirmed that Insulin-like growth factor-1 (IGF-1) is involved in the initiation and progression of puberty. With this inspection, we assumed that the IGF-1 level might be correlated with the pubertal stage in central precocious puberty. This study aimed to investigate the value of IGF-1 levels in screening central precocious puberty. The medical records of 359 patients with a chief complaint of premature breast development and visited the pediatric endocrinology clinic in Myongji Hospital from January 2017 to October 2022 were reviewed. Two hundred thirty-three girls with central precocious puberty (CPP) and 126 girls with premature thelarche (PT) diagnosed were enrolled. Each subject had IGF-1 and GnRH stimulation test results. The anthropometric data between CPP and PT showed no statistical differences except for weight and the existence of lipomastia. The hormonal indicators including peak luteinizing hormone (peak LH), peak follicular stimulating hormone (peak FSH), and estradiol were statistically different between the two groups (P &lt; 0.001). IGF-1 levels were significantly higher in CPP group than in PT group. The IGF-1 levels were positively correlated with peak LH, the diagnostic indicator of CPP. The area under the curve (AUC) of IGF-1 was 0.709. IGF-1 levels were correlated with the diagnostic indicator of CPP. IGF-1 would be a useful tool for screening CPP. Keywords: girls; IGF-1; GnRH stimulation test; precocious puberty.
Presentation: Thursday, June 15, 2023
THU201 Atypical Presentation Of Kallmann Syndrome With A Rare Genetic Mutation
Authors: Montgomery Emily L , Thrasher Bradly , Watson Sara 
Published: October 2023

Abstract
Disclosure: E.L. Montgomery: None. B. Thrasher: None. S. Watson: None.
Kallmann Syndrome presents as idiopathic hypogonadotropic hypogonadism with additional findings of hyposmia or anosmia and midline facial defects, including cleft lip/palate. We present a case of Kallmann Syndrome due to a rare genetic mutation with absent Mullerian structures. A 15 year, 6 month old female with history of cleft lip and palate and short stature was referred for primary amenorrhea. Clinical history was notable for limited sense of smell and no signs of puberty, including thelarche or adrenarche. Family History unknown (adopted). Significant physical exam findings include tanner 1 breast, no pubic or axillary hair, normal external female genitalia without clitoromegaly, unestrogenized vaginal introitus. Height 147cm (0.88%ile for age). Lab evaluation consisted of: LH 0.66 mIU/ml (2.4-12.6 mIU/ml), FSH 1.63 mIU/ml (3.5-12.5 mIU/ml), prolactin 11.30 ng/ml (4.79-23.30 ng/ml), BhCG negative, testosterone 8 ng/dl (2-17 ng/dl), free testosterone 1.1 pg/ml (&lt;2.2 pg/ml), estradiol 3.0 pg/ml (9.0-249.0 pg/ml), AMH 2.46 ng/ml (1.05-12.86 ng/ml), thyroid function testing and growth factors normal. Imaging included pelvic ultrasound that showed no uterus or gonads. An MRI was obtained that confirmed these findings and also a blind-ending vaginal canal. While the presentation is suggestive of Kallmann Syndrome, the lack of Mullerian structures on imaging has not previously been described. Further evaluation included karyotype (46, XX) and hypogonadotropic hypogonadism genetic panel that identified a mutation in the FGFR1 gene with c.2172C&gt;G (p.Asn724Lys), heterozygous, variant of uncertain significance. Estrogen replacement therapy was initiated with subsequent expected pubertal progression. Repeat imaging after seven months of treatment demonstrated presence of normal developing uterus and bilateral ovaries. Clinical Lesson/Conclusion: 1.Rare mutation with now 3 reports suggesting it is a true pathologic variant2.Unique presentation with hypoplastic Mullerian structures not detected on imaging.This patient’s particular variant has previously been described in in 2 individuals (mother/son) with features of Kallmann Syndrome (PMID: 16606836) with normal and partial puberty respectively, increasing the suspicion that this variant is pathogenic. Newly described FGFR1 variant associated with Kallmann Syndrome / hypogonadotropic hypogonadism. Kallmann Syndrome is not associated with lack of Mullerian structures, however this patient presented with features of Kallmann Syndrome and imaging that did not demonstrate presence of Mullerian structures. Since initiating estrogen therapy, she has had appropriate development of uterus and ovaries. This case demonstrates that prior to estrogen therapy, patients with Kallmann Syndrome may have underdeveloped Mullerian structures that not recognized on imaging prior to estrogen replacement therapy.
Presentation: Thursday, June 15, 2023
THU215 Treatment Of Childhood-onset Craniopharyngioma Patients Using Proton Beam Therapy Versus Photon-based Radiation Therapy In The Prospective Kraniopharyngeom 2007 Trial
Authors: Friedrich Carsten , Boekhoff Svenja , Sowithayasakul Panjarat , Eveslage Maria , Beckhaus Julia , Bison Brigitte , Timmermann Beate , Muller Hermann Lothar 
Published: October 2023

Abstract
Disclosure: C. Friedrich: None. S. Boekhoff: None. P. Sowithayasakul: None. M. Eveslage: None. J. Beckhaus: None. B. Bison: None. B. Timmermann: None. H.L. Muller: None.
Proton beam therapy (PBT) compared to photon-based radiotherapy (XRT) offers the benefit to administer lower radiation doses to critical organs thereby possibly minimizing the risk of sequelae in patients with residual craniopharyngiomas (CP) after hypothalamus-sparing surgery. The validation in large CP patient cohorts is still pending. Of 290 childhood-onset CP patients included 2007-2019 in the prospective multicenter trial KRANIOPHARYNGEOM 2007, 99 (34%) received external RT (65% PBT, 35% XRT). Outcome was compared between the different groups in terms of overall (OS) and event-free survival (EFS), quality of life (QoL using PEDQOL), functional capacity (FMH), and auxological data (BMI and height SDS) one, three and five years after irradiation/CP diagnosis. PBT became the predominant irradiation technique during the study period (used in 23% and 77% of all irradiated patients registered within the first and second half of the enrollment period, respectively). PBT as well as XRT were associated with high (p&lt;0.001) EFS (PBT: 0.917 ± 0.040; XRT: 0.940 ± 0.041) compared to non-RT (EFS: 0.669 ± 0.044). OS was similar in all groups. No differences between PBT, XRT and non-RT CP patients concerning functional capacity and anthropometric parameters (height SDS, BMI SDS) have been obtained. Only in the PEDQOL domain “physical function”, proxy-assessed QoL was lower one year after PBT when compared to XRT treated and non-irradiated CP patients. PBT is similar efficient in preventing relapses in childhood-onset CP patients. During follow-up, clinically relevant differences between PBT and XRT in terms of QoL, functional capacity and degree of obesity as a marker of hypothalamic syndrome were not detectable. While PBT is increasingly applied, studies on larger CP cohorts with longer follow-up after RT are warranted to analyze, whether it can prevent sequelae such as hypothalamic syndrome and severe obesity compared to XRT.
Presentation: Thursday, June 15, 2023
THU218 Congenital Craniopharyngioma - Cases Recruited In The German Kraniopharyngeom Trials And Review Of The Literature
Authors: Boekhoff Svenja , Beckhaus Julia , Bison Brigitte , Friedrich Carsten , Muller Hermann Lothar 
Published: October 2023

Abstract
Disclosure: S. Boekhoff: None. J. Beckhaus: None. B. Bison: None. C. Friedrich: None. H.L. Muller: None.
Background: Craniopharyngiomas (CP) are rare malformational tumors. Clinical presentation and outcome of patients with congenital CP (cCP) are not clear and refer mainly to few case reports in the literature. The aim of this study was to analyze clinical presentation and outcome in patients with cCP. Clinical cases: Seven hundred and nine patients diagnosed with adamantinomatous CP were recruited 1999-2021 in HIT-ENDO, KRANIOPHARYNGEOM 2000 / 2007 / Registry 2019 and prospectively observed. In 3 cases, cCP was diagnosed prenatally and in one case at the 2nd day of life. Pre- and perinatal diagnostic findings, postnatal evaluation, therapeutic interventions and outcome in these 4 cases of cCP were analyzed. When compared to cases of cCP reported in the literature, more recent cases like our reported cCP have an overall better prognosis with regard to survival and sequelae. Two of our 4 cCP suffered from hemiparesis and one patient presented with mild motor retardation. In contrast to historical reports (lethal rate of &gt;50%), all patients in our report recruited after 2000 survived. Prenatal routine ultrasound examination was the usual diagnostic procedure leading to diagnosis of cCP. Tumor resection was performed during early postnatal period (range: 11 - 51 days of age). Complete resection of the mostly large sized tumors could be achieved in two of four patients with cCP. Conclusion: Based on improvements of diagnostic and therapeutical methods and techniques, earlier prenatal diagnosis of cCP should lead to intrauterine transfer of cCP patients to a specialized center for postnatal treatment of newborns with sellar masses by a multidisciplinary team to secure an improved prognosis of these patients.
Presentation: Thursday, June 15, 2023
THU219 Vascular Damage After Craniopharyngioma
Authors: Beckhaus Julia , Boekhoff Svenja , Bison Brigitte , Friedrich Carsten , Muller Hermann Lothar 
Published: October 2023

Abstract
Disclosure: J. Beckhaus: None. S. Boekhoff: None. B. Bison: None. C. Friedrich: None. H.L. Muller: None.
Craniopharyngiomas are rare, embryonic, malformational tumors of the (supra-)sellar region. Due to tumor and/or treatment-related hypothalamic lesions, patients develop morbid obesity. Obesity is a major vascular risk factor, leading to reduced 20-year overall survival and a 3- to 19-fold higher cardiovascular mortality after craniopharyngioma compared to the general population. An analysis within the Childhood Cancer Survivor Study (CCSS) revelaed a 10-fold higher relative risk for stroke in adult survivors of childhood/young adult cancers compared to their siblings. To study craniopharyngioma-specific risk factors for vascular damages we searched three databases (Pubmed, CINAHL and Web of Science) and included 49 articles after title and abstract screening. Eligible studies were case reports, cohort and cross-sectional studies. Neurovascular damages due to surgical interventions included cerebral infarcts, stroke, aneurysms, anterior/middle cerebral artery syndrome (ACA/MCA), cerebral venous sinus thrombosis, and seizures. Radiation-induced vascular disease described Moyamoya syndrome, radionecrosis and thrombosis. Tumor-induced inflammation is suspected to play a causal role in the etiology of vascular complications in proximity of the tumor. Therefore, early diagnostics such as echocradiography or cardial MRI and risk-adapted prevention and treatment options for vascular disease are needed to improve long-term prognosis after craniopharyngioma treatment. This review summarizes the available evidence for vascular disease after pediatric- and adult-onset craniopharyngioma to derive possible treatment pathways. Individualized, tertiary prevention programs are required for craniopharyngioma patients and survivors to overcome or reduce the risk of vascular complications and elevate their quality of survival.
Presentation: Thursday, June 15, 2023
THU618 Adrenal Cell Carcinoma Presenting With Post-menopausal Bleeding And IGF-2 Induced Hypoglycaemia
Authors: Lonergan Eibhlin Marie , Joyce Tan Lok Yi , Ali Elsheikh , Joyce Caroline Martha , Conlon Niamh , O'Sullivan Adrian , O'Halloran Domhnaill Jude 
Published: October 2023

Abstract
Disclosure: E.M. Lonergan: None. L.J. Tan: None. E. Ali: None. C.M. Joyce: None. N. Conlon: None. A. O'Sullivan: None. D.J. O'Halloran: None.
Background: Non-islet cell tumour hypoglycaemia (NICTH) as a result of IGF-2 secretion is rare with a few case reports associated with adrenal tumours. Clinical Case: We present the case of a 59-year-old female initially presenting to gynaecology services with post-menopausal bleeding due to endometrial hyperplasia. Serum testosterone, oestradiol and adrenal androgens were found to be elevated and LH and FSH suppressed. A subsequent CT adrenals demonstrated a 12.8 x 13.2 x 10.6cm left adrenal mass and she failed a 1mg overnight dexamethasone suppression test. In the interim, while undergoing evaluation, the patient presented to A+E Department with point-of-care confirmed hypoglycaemia with a capillary blood glucose of 1.6mmol/L and neuroglycopaenic symptoms. There was no history of diabetes mellitus, prolonged fasting, access to sulphonylureas or insulin. During a supervised fast, symptomatic hypoglycaemia occurred within 5 hours at 2.0mmol/L fulfilling Whipple’s triad. Results of samples taken during hypoglycaemia revealed an elevated IGF-2 : IGF-1 ratio of 60.7 (normal &lt;10) with a low paired C-peptide, insulin and pro-insulin, consistent with a suspected IGF-2-secreting tumour. Hypoglycaemia was successfully managed with low glycaemic index foods and clinical nutrition input. Radical surgical excision was undertaken including left adrenalectomy, nephrectomy, partial pancreatectomy and splenectomy. Post-operative pathology revealed an adrenocortical carcinoma (ACC) measuring 16.4cm in maximum dimension; Ki67 12%; Weiss score 5; lymph nodes negative. Tissue has been stained for IGF-2-IR. Post-operative IGF-2 : IGF-1 ratio normalised to 3.4. The patient is under active follow up with 3-monthly surveillance CT-TAP and has declined Mitotane therapy at present. Conclusion: This is a rare case of ACC secreting multiple hormones, resulting in post-menopausal bleeding and IGF-2 mediated hypoglycaemia.
Presentation: Thursday, June 15, 2023