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BACKGROUND: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2. Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum. METHODS: We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays. MAIN RESULTS: We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3, respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC. CONCLUSIONS: This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC/EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes.
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Síndrome de Ellis-Van Creveld , Linaje , Fenotipo , Humanos , Síndrome de Ellis-Van Creveld/genética , Síndrome de Ellis-Van Creveld/patología , Masculino , Femenino , Niño , Proteínas de la Membrana/genética , Mutación , Preescolar , Proteína Gli3 con Dedos de Zinc/genética , Adolescente , Adulto , Proteínas del Tejido Nervioso/genética , Estudios de Cohortes , Lactante , Proteínas/genética , Estudios Retrospectivos , Péptidos y Proteínas de Señalización IntercelularRESUMEN
BACKGROUND: Adult patients diagnosed with type 1 diabetes mellitus are at risk for ventricular arrhythmias and sudden cardiac death. AIM: The objective of our study is to evaluate the electrocardiographic data of children diagnosed with type 1 diabetes mellitus and to determine the possibility of arrhythmia in order to prevent sudden death. METHODS: Electrocardiographic data of 60 patients diagnosed with type 1 diabetes mellitus and 86 controls, who were compatible with the patient group in terms of age and gender, were compared. RESULTS: The duration of diabetes in our patients with type 1 diabetes mellitus was 5.23 ± 1.76 years, and the haemoglobin A1c levels were 9.63% ± 1.75%. The heart rate, QRS, QT maximum, QT dispersion, QTc minimum, QTc maximum, QTc dispersion, Tp-e maximum, Tp-e maximum/QTc maximum and the JTc were significantly higher compared to the control group. There was no significant correlation between the duration of type 1 diabetes mellitus and HbA1c levels and the electrocardiographic data. CONCLUSION: We attributed the lack of a significant correlation between the duration of type 1 diabetes mellitus and the haemoglobin A1c levels and the electrocardiographic data to the fact that the duration of diabetes was short, since our patients were children. We believe that patients with type 1 diabetes mellitus should be followed up closely in terms of sudden death, as they have electrocardiographic changes that may cause arrhythmias compared to the control group. However, more studies with longer follow-up periods are necessary to support our data.
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Diabetes Mellitus Tipo 1 , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , Estudios de Casos y Controles , Niño , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Diabetes Mellitus Tipo 1/complicaciones , Electrocardiografía , HumanosRESUMEN
INTRODUCTION: Leydig cell hypoplasia (LCH) is an autosomal recessive disease that causes 46, XY sex development disorder. The patients with LCH are usually in the female phenotype and are presented with the complaints of no breast development and primary amenorrhea. In this article, the cases of three siblings who presented with primary amenorrhea and who had LCH were presented. CASE: A 16-year-old patient with female phenotype is presented with primary amenorrhea. Breast development was at Tanner stage 1, the external genitalia were completely in female phenotype. The karyotype was determined as 46, XY. The hormonal analyses revealed that the testosterone synthesis was insufficient despite the high level of luteinizing hormone (LH). Cortisol, ACTH, 17-Hydroxyprogesterone, and AMH levels were normal. LCH diagnosis was considered in the patient with elevated LH and no testosterone synthesis. A new mutation of homozygous c.161 + 4A > G was detected in LHCGR gene. The same mutation was detected in the patient's two siblings with female phenotype and 46, XY karyotype. CONCLUSION: In patients presenting with primary amenorrhea and karyotype 46, XY, there is no testosterone synthesis and if there is LH elevation, LCH should be considered. We found a novel variant in the LHCGR gene in three siblings with karyotype 46, XY and female phenotype.
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Trastorno del Desarrollo Sexual 46,XY/genética , Receptores de HL/genética , Testículo/anomalías , Adolescente , Trastorno del Desarrollo Sexual 46,XY/sangre , Trastorno del Desarrollo Sexual 46,XY/fisiopatología , Femenino , Homocigoto , Humanos , Masculino , Hermanos , Testículo/fisiopatologíaRESUMEN
Aims: 17α-hydroxylase deficiency is a rare form of congenital adrenal hyperplasia (CAH) which is inherited autosomal recessive. It occurs result of a mutations in gene cytochrome (CYP)17A1, which encodes both 17α-hydroxylase and 17,20-lyase enzymes. The main clinical findings of the disease are delayed puberty, primary amenorrhea in females, and disorders of sex development (DSD) in males. Also, hypertension and hypokalemia can be seen in both sexes. In this paper, we describe the clinical and genetic changes of two patients with 46,XY and 46,XX karyotypes from two different families who were diagnosed with complete 17α-hydroxylase enzyme deficiency.Methods: In this study various methods including clinical, hormonal, radiological and genetic analyzes were used. Blood samples were obtained for genetic tests. Genomic DNA was extracted from peripheral blood leukocytes, and coding sequence abnormalities of the CYP17 gene were assessed by polymerase chain reaction and direct sequencing analysis.Results: 17α-hydroxylase deficiency was diagnosed in 2 patients with 46,XX and 46,XY karyotype who presented with hypertension and delayed puberty. The pQ80 * (c.238C > T) mutation detected in both cases was evaluated as a novel variant.
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Trastornos del Desarrollo Sexual 46, XX/genética , Trastorno del Desarrollo Sexual 46,XY/genética , Polimorfismo de Nucleótido Simple , Pubertad Tardía/genética , Esteroide 17-alfa-Hidroxilasa/genética , Trastornos del Desarrollo Sexual 46, XX/diagnóstico , Adolescente , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Trastorno del Desarrollo Sexual 46,XY/diagnóstico , Femenino , Humanos , Cariotipo , Mutación Missense , Pubertad Tardía/diagnósticoRESUMEN
GLI1, GLI2 and GLI3 form a family of transcription factors which regulate development by mediating the action of Hedgehog (Hh) morphogens. Accordingly, inactivating variants in GLI2 and GLI3 are found in several developmental disorders. In contrast, loss-of-function mutations in GLI1 have remained elusive, maintaining enigmatic the role of this gene in the human embryo. We describe eight patients from three independent families having biallelic truncating variants in GLI1 and developmental defects overlapping with Ellis-van Creveld syndrome (EvC), a disease caused by diminished Hh signaling. Two families had mutations in the last exon of the gene and a third family was identified with an N-terminal stop gain variant predicted to be degraded by the NMD-pathway. Analysis of fibroblasts from one of the patients with homozygous C-terminal truncation of GLI1 demonstrated that the corresponding mutant GLI1 protein is fabricated by patient cells and becomes upregulated in response to Hh signaling. However, the transcriptional activity of the truncated GLI1 factor was found to be severely impaired by cell culture and in vivo assays, indicating that the balance between GLI repressors and activators is altered in affected subjects. Consistent with this, reduced expression of the GLI target PTCH1 was observed in patient fibroblasts after chemical induction of the Hh pathway. We conclude that GLI1 inactivation is associated with a phenotypic spectrum extending from isolated postaxial polydactyly to an EvC-like condition.
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Síndrome de Ellis-Van Creveld/genética , Proteína con Dedos de Zinc GLI1/genética , Niño , Síndrome de Ellis-Van Creveld/metabolismo , Síndrome de Ellis-Van Creveld/patología , Exones , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Regulación del Desarrollo de la Expresión Génica , Silenciador del Gen , Proteínas Hedgehog/metabolismo , Humanos , Lactante , Recién Nacido , Masculino , Linaje , Fenotipo , Polidactilia/genética , Polidactilia/metabolismo , Cultivo Primario de Células , Transducción de Señal , Transactivadores/genética , Transcripción Genética , Proteína con Dedos de Zinc GLI1/metabolismoRESUMEN
BACKGROUND: Studies on adults have shown increased dispersion of QT and corrected QT (QTc), peak-to-end interval of the T wave (Tp-e), Tp-e/QT ratio, and Tp-e/QTc ratio in subclinical hypothyroidism (SH), but there have been no pediatric studies. MATERIALS AND METHODS: A total of 40 SH patients were compared with 40 healthy children in respect to serum thyroid-stimulating hormone (TSH), serum-free level of triiodothyronine, and free level of thyroxine (fT4). SH diagnosis was accepted as TSH above the laboratory accepted upper limit (>4.2 mU/L) and normal fT4 values. The patient and control group data were compared by calculating the QT interval, QTc, QT dispersion (QTd), QTc dispersion (QTcd), Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio on 12-lead surface electrocardiogram. RESULTS: The mean age was 7.91 ± 3.6 years in the SH group and 8.8 ± 2.4 years in the control group. In the SH group, the minimum QT (QTmin) was determined to be statistically significantly lower (P < 0.001) and maximum QT (QTmax), QTd, QTcd, Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio were statistically significantly higher (P = 0.028, P < 0.001, P = 0.003, P < 0.001, P = 0.001, P < 0.001, respectively). A positive correlation was determined between TSH and QTmax (r: +0.331, P = 0.037). CONCLUSIONS: The current study is the first to have shown significantly increased QTd, QTcd, Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio in children diagnosed with SH. A positive correlation was determined between TSH and maximum QT values, Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio. These results suggest the need to further assess the long-term risks of prolonged QT dispersion in the setting of subclinical hypothyroidism.
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Arritmias Cardíacas/fisiopatología , Hipotiroidismo/fisiopatología , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Electrocardiografía , Femenino , Humanos , Masculino , Hormonas Tiroideas/sangreRESUMEN
Objective: Noonan syndrome (NS) is characterized by dysmorphic facial features, short stature, congenital heart defects, and varying levels of developmental delays. It is a genetic, multisystem disorder with autosomal dominant inheritance and is the most common of the RASopathies. In approximately 50% of patients, NS is caused by variants in the Protein Tyrosine Phosphatase Non-Receptor Type 11 (PTPN11) gene. The aim of this study was to evaluate two patients with a previously reported PTPN11 homozygous variant for the first time and seven other kindred members carrying the same heterozygous variant in terms of clinical, biochemical, genetic, and response to treatment. Methods: Nine patients diagnosed with NS due to the same variants in the PTPN11 gene were included in the study. Results: The median (range) age at diagnosis was 11.5 (6.8-13.9) years and the mean follow-up duration was 4.7 (1-7.6) years. In eight patients (88.9%), short stature was present. The height standard deviation score of the patients on admission was -3.24±1.15. In six of the patients, growth hormone treatment was initiated. Cardiovascular or bleeding disorders were not detected in any of the patients. Three (33.3%) had hearing loss, two (22.2%) had ocular findings and one (11.1%) had a horseshoe kidney. The mean psychomotor development performance score was 84.03±17.09 and the verbal score was 82.88±9.42. Genetic analysis revealed a variant in the PTPN11 gene [c.772G>A; (p.Glu258Lys)] that had been previously described and was detected in all patients. Two patients were homozygous for this variant and short stature was more severe in these two. Conclusion: A previously described in PTPN11 affected nine members of the same kindred, two with homozygous inheritance and the remainder being heterozygous. To the best of our knowledge, these are the first homozygous PTPN11 case reports published, coming from two related consanguineous families.
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Enanismo , Síndrome de Noonan , Humanos , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Heterocigoto , FenotipoRESUMEN
OBJECTIVES: Central precocious puberty (CPP) is the onset of puberty before the age of 8 in girls and 9 in boys. The primary goal of CPP treatment is control and arrest of puberty development. In this study, it was aimed to determine the factors associated with final height in patients who received gonadotropin-releasing hormone analogs (GnRHa) treatment and reached their final height. METHODS: From the medical records of the patients, age on admission, bone age (BA), weight-standard deviation score (SDS), height-SDS, BMI-SDS, target height-SDS, basal LH, FSH, E2, age at menarche, and pelvic USG findings were obtained. RESULTS: The mean age on admission of the 67 female patients was 7.5 ± 0.60 years. On admission, 4.5â¯% of the patients were obese and 19.4â¯% were overweight. There was no difference between BMI-SDS at admission and after treatment. The mean age at menarche was 11.57 ± 0.78 years. About 58.2â¯% of the patients reached the target height, 35.8â¯% exceeded the target height, and 6â¯% were below the target height. The mean height-SDS and predicted adult height (PAH) on admission were better in patients who exceeded the target height. It was determined that target height-SDS had a positive effect on delta height-SDS, while BA/CA ratio had a negative effect. CONCLUSIONS: It was found that GnRHa treatment did not have a negative effect on BMI-SDS. It was shown that 94â¯% of the patients who received GnRHa treatment reached the target height, and in fact, 35.8â¯% exceeded the target height. A greater final height may be associated with good height-SDS and PAH values on admission.
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Estatura , Hormona Liberadora de Gonadotropina , Pubertad Precoz , Humanos , Pubertad Precoz/tratamiento farmacológico , Femenino , Niño , Estudios Retrospectivos , Hormona Liberadora de Gonadotropina/análogos & derivados , Menarquia , Masculino , Pronóstico , Índice de Masa Corporal , Estudios de SeguimientoRESUMEN
PURPOSE: 17α Hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia, typically diagnosed in late adolescence with symptoms of pubertal delay and hypertension. This study aimed to determine the clinical and laboratory characteristics of 17OHD cases and gather data on disease management. METHODS: Data from 97 nationwide cases were analyzed using the CEDD-NET web system. Diagnostic, follow-up findings, and final heights of patients were evaluated. RESULTS: Mean age at admission was 13.54 ± 4.71 years, with delayed puberty as the most common complaint. Hypertension was detected in 65% at presentation; hypokalemia was present in 34%. Genetic analysis revealed Exon 1-6 homozygous deletion as the most frequent mutation, identified in 42 cases. Hydrocortisone replacement was universal; pubertal replacement was administered to 66 cases. Antihypertensive treatment was required in 57 (90%) patients. Thirty-seven cases reached final height, with an average SD of 0.015 in 46,XX and -1.43 in 46,XY. Thelarche and pubarche did not develop properly in some cases despite estradiol treatment. CONCLUSION: This study represents the largest cohort of pediatric cases of 17-hydroxylase deficiency (17OHD) documented in the literature. Hypertension and hypokalemia can serve as guiding indicators for early diagnosis.The final height is typically considered to be normal. The relationship between genotype and phenotype remains elusive. The initial genetic test for exon 1-6 deletions may be MLPA in our region.
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Hiperplasia Suprarrenal Congénita , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Hiperplasia Suprarrenal Congénita/genética , Estudios de Cohortes , Hipertensión/genética , Hipopotasemia/genética , Pubertad Tardía/genética , Esteroide 17-alfa-Hidroxilasa/genética , Turquía/epidemiologíaRESUMEN
Aim: In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast development started before the age of 8. Materials and Methods: The chronological age, anthropometric measurements, bone age (BA), hormone test results and pelvic ultrasonography findings of the cases were recorded. Those with a peak luteinizing hormone (LH) level of ≥5 IU/L in the gonadotropin-releasing hormone (GnRH) stimulation test were classified as CPP and those with a peak LH level of <5 IU/L were classified as prepubertal cases. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic accuracy of laboratory variables. Findings: A total of 297 female cases were included in the study. The age at the time of admission, height-standard deviation score (SDS), BA, the long axis of the uterus and the volumes of the right and left ovaries of the cases diagnosed with CPP were found to be significantly higher than those of the prepubertal group. The cut-off value providing the best sensitivity (99%) and specificity (99%) for the peak LH was found to be 4.55; the cut-off value providing the best sensitivity (94%) and specificity (85%) for the peak LH/follicle-stimulating hormone (FSH) ratio was found to be 0.32 and the cut-off value providing the best sensitivity (47%) and specificity (93%) for the basal LH was found to be 0.13. Conclusion: We believe that in female cases with early breast development, a peak LH level of ≥4.55 may possibly indicate CPP and a basal LH level of <0.13 can significantly rule out CPP.
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Congenital generalized lipodystrophy (CGL) is a rare, autosomal recessive disorder characterized by an almost complete absence of body fat. In CGL, patients may have hyperphagia due to leptin deficiency. Recombinant human leptin (metreleptin) has been suggested as an effective treatment option. We present successful treatment with metreleptin in a boy with CGL and results from the first year of follow-up. An eight-month-old boy presented with excessive hair growth and a muscular appearance. On examination he had hypertrichosis, decreased subcutaneous adipose tissue over the whole body and hepatomegaly. Laboratory investigations revealed hypertriglyceridemia, hyperinsulinemia, elevated liver transaminases and low leptin levels. Molecular genetic analysis detected a homozygous, c.465_468delGACT (p.T156Rfs*8) mutation in the BSCL2 gene. A diagnosis of CGL type 2 was considered. Despite dietary intervention, exercise, and treatment with additional omega-3 and metformin, the hypertriglyceridemia, hyperinsulinemia, and elevated liver transaminase levels worsened. Metreleptin treatment was started and after one year hyperphagia had disappeared, and there was dramatic improvement in levels of insulin, hemoglobin A1c, triglycerides and liver transaminases. Hepatosteatosis was lessened and hepatosplenomegaly was much improved. Metreleptin appears to be an effective treatment option in children with CGL that remarkably improved metabolic complications in the presented case. Initiation of metreleptin treatment in the early period may decrease mortality and morbidity, and increase the quality of life in children with CGL.
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Subunidades gamma de la Proteína de Unión al GTP , Hiperinsulinismo , Hipertrigliceridemia , Lipodistrofia Generalizada Congénita , Niño , Humanos , Lactante , Masculino , Subunidades gamma de la Proteína de Unión al GTP/genética , Subunidades gamma de la Proteína de Unión al GTP/metabolismo , Hiperinsulinismo/complicaciones , Hiperfagia/complicaciones , Hipertrigliceridemia/complicaciones , Leptina/genética , Leptina/metabolismo , Lipodistrofia Generalizada Congénita/tratamiento farmacológico , Lipodistrofia Generalizada Congénita/genética , Lipodistrofia Generalizada Congénita/complicaciones , Mutación , Calidad de VidaRESUMEN
AIM: Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia, and alacrimia. This disorder is caused by mutations in the AAAS gene. The aim of this study is to discuss the clinical, laboratory and molecular genetic analysis results of 12 patients with TAS. METHOD: We evaluated 12 patients from 8 families. Clinical and laboratory data were retrospectively collected from the medical records of the patients in the database for the period 2015-2020. All exons and exon-intron junctions of the AAAS gene were evaluated by next-generation sequencing method. Detected variants were classified according to American Collage of Medical Genetics criteria. RESULTS: Alacrimia was found in all patients (100%); achalasia was found in 10 patients (83.3%) and adrenal insufficiency was found in 10 patients (83.3%). In addition, hyperreflexia(6/12), learning disability(5/12), hypernasal speech(5/12), muscle weakness(8/12), delayed walking(7/12), delayed speech(6/12), excessive sweating(7/12), optic atrophy(1/12), epilepsy(1/12), palmoplantar hyperkeratosis(5/12), multiple dental caries(9/12), atrophy of the thenar/hypothenar muscles(4/12) and short stature(4/12) were detected. The DHEA-S levels were measured in 10 patients and were found to be low in 8 of them. In all patients, the sodium and potassium levels were found to be normal. AAAS gene sequencing revealed four previously reported c.1066_1067del (p.Leu356fs*8), c.1432 C > T (p.Arg478*), c.688 C > T (p.Arg230*), and c.1368_1372del (p.Gln456fs*38) variants and two novel homozygous c.1250-1 G > A and c.398_399 + 2del variants in the AAAS gene. CONCLUSION: We detected two novel variants in the AAAS gene. While the classic triad is present in 66.7% of the cases, neurological dysfunction, skin and dental pathologies also occur quite frequently. The earliest and most common finding of TAS is alacrimia. Therefore, adrenal insufficiency should be investigated in all patients with alacrimia and if necessary, genetic analysis should be performed for TAS. In addition, TAS should be followed up with a multidisciplinary approach since it involves many systems.
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Insuficiencia Suprarrenal , Caries Dental , Acalasia del Esófago , Humanos , Acalasia del Esófago/genética , Turquía/epidemiología , Estudios Retrospectivos , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/genéticaRESUMEN
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 Diyarbakir in 2011. The aim of this study was to evaluate the current incidence rate of pediatric T1D in Diyarbakir, and compare the incidence, and clinical and presenting characteristics of more recent cases with those reported in our first report. Methods: Hospital records of patients diagnosed with T1D in Diyarbakir 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: 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%. Conclusion: The annual incidence of pediatric T1D in Diyarbakir 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.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Adolescente , Anciano , Niño , Diabetes Mellitus Tipo 1/complicaciones , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/etiología , Femenino , Humanos , Incidencia , Masculino , Turquía/epidemiologíaRESUMEN
AIM: 17α-hydroxylase enzyme deficiency is a rare form of congenital adrenal hyperplasia (CAH) and is caused by mutations in the CYP17A1 gene. The main clinical findings are delayed puberty and primary amenorrhea in girls, and disorders of sex development in boys. It can also cause hypertension and hypokalemia in both genders. In this study, we aimed to present the clinical, laboratory and genetic results of 13 patients from eight different families who were diagnosed with complete 17α-hydroxylase enzyme deficiency. METHODS: The age, symptoms, anthropometric measurements, blood pressure, Tanner stages, and hormonal and chromosome analysis results at the time of admission were recorded from the medical records of the patients. Whole gene next-generation sequencing of CYP17A1 gene was performed to detect mutations. Multiplex ligation dependent probe amplification (MLPA) method were used to detect deletions in the seven patients who had no point mutation were detected in the CYP17A1 gene. RESULTS: The average age of the patients at the time of admission was 14.8 (range: 12.9-16.6) years. Also at this time, all patients were in adolescence and were raised as females. The karyotypes of eight patients were 46,XY, and of five patients were 46,XX. Ten patients presented with delayed puberty and primary amenorrhea, one patient with delayed puberty and hypertension, and two patients with hypertension and/or hypokalemia. Hypertension and hypokalemia were detected in nine and seven patients, respectively. CONCLUSIONS: P450c17 enzyme deficiency should be considered in patients presenting with delayed puberty or primary amenorrhea in the adolescence period and diagnosed with hypergonadotropic hypogonadism, if hypertension and hypokalemia accompany. Early diagnosis prevents the occurrence of important health problems such as hypertension, psychological problems, and gender identity disorders, which affect the majority of these patients.
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Hiperplasia Suprarrenal Congénita , Pubertad Tardía , Adolescente , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Amenorrea/genética , Niño , Femenino , Identidad de Género , Humanos , Masculino , Oxigenasas de Función Mixta/genética , Mutación , Esteroide 17-alfa-Hidroxilasa/genéticaRESUMEN
INTRODUCTION: The luteinizing hormone/choriogonadotropin receptor (LHCGR) plays a critical role in sexual differentiation and reproductive functions in men and women. Inactivating mutations in this gene lead to Leydig cell hypoplasia (LCH), and cause disorders of sex development (DSD) in patients with 46,XY. In this study, it was aimed to discuss the clinical, laboratory and molecular genetic analysis results of nine patients with 46,XY karyotype who had mutations in the LHCGR gene. MATERIALS AND METHODS: The ages, complaints, anthropometric measurements and hormonal results (follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone) of the patients at the time of admission were recorded retrospectively from their medical records. The mutations in the LHCGR gene were investigated using the Sanger sequencing method. FINDINGS: In this study, LHCGR gene mutations were detected in a total of nine patients as a result of the analysis of the index patients presenting with primary amenorrhea from four different families and the examination of the families. In the first three families with no consanguinity between, the same mutation was detected in seven patients in total (Homozygous c.161 + 4A > G). A different mutation was detected in the fourth family (Homozygous p.A483D c.1448C > A). CONCLUSION: In this study, nine patients with karyotype 46,XY, most of whom presented with the complaint of delayed puberty/primary amenorrhea, were diagnosed with LCH. Especially in patients, in whom the elevation of LH is pronounced and there is no testosterone synthesis, LCH should be considered.
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Amenorrea , Receptores de HL , Amenorrea/genética , Trastorno del Desarrollo Sexual 46,XY , Femenino , Humanos , Masculino , Mutación , Receptores de HL/genética , Estudios Retrospectivos , Testículo/anomalíasRESUMEN
AIM: There is no clear consensus on whether a cranial MRI should be performed in all cases of central precocious puberty(CPP). In this study, we aimed at evaluating the incidence of intracranial lesions and analyzing cranial imaging results in females with CPP. METHODS: In the retrospective study medical records of the case, the age at the time of admission, anthropometric measurements, bone age, Tanner stages, serum follicle-stimulating hormone (FSH), serum luteinizing hormone(LH), serum estradiol (E2) levels, the peak LH level during the gonadotropin-releasing hormone (GnRH) stimulation test and the cranial MRI findings at the time of the diagnosis of CPP were collected. RESULTS: The mean age diagnosis of the 154 girls included in the study was 6.9 ±1.08. Nine (5.8%) of 154 patients were diagnosed with organic-caused CPP. Four of the nine cases diagnosed with organic CPP had a previously known CNS pathology. The other five cases did not have any neurological findings at the time of diagnosis. Incidental lesions were detected at cranial MRI of nine of the 145 cases diagnosed with idiopathic CPP. The basal E2, basal LH, basal FSH, peak LH and peak LH/FSH levels of the cases with organic CPP were higher than those with idiopathic CPP. CONCLUSIONS: In our study, approximately 90% of organic CPP due to intracranial lesions were between 6-8 years. Therefore, we believe that cranial imaging should be performed in all females with CPP.
RESUMEN
OBJECTIVES: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by isolated glucocorticoid deficiency. Melanocortin receptor 2 (MC2R) mediates the functions of adrenocorticotropic hormone (ACTH) in the adrenal cortex. MC2R accessory protein (MRAP) is a transmembrane protein involved in the trafficking of MC2R to the cell surface. Mutations in MC2R and MRAP genes cause FGD type 1 and 2. In the present case series, we evaluate the clinical characteristics and long-term follow-up of six cases with FGD due to mutations in MC2R and MRAP. CASE PRESENTATION: Data of six cases with FGD (five with mutations in MC2R and one with a mutation in MRAP) who were being followed at our paediatric endocrine centre was evaluated. Diagnosis of FGD was considered in case of elevated ACTH and inappropriately low cortisol level, and exclusion of other aetiologies. The main presenting complaints were hyperpigmentation and hypoglycaemic convulsion in all cases. During a follow-up period of 26-115 months, one patient with homozygous 560delT mutation in MC2R, one female with G226R mutation in MC2R and one female with IVS3ds+1delG mutation in MRAP had a neurodevelopmental delay (NDD), while the other three patients had normal neurodevelopment. CONCLUSIONS: FGD patients due to MC2R and MRAP mutations with early diagnosis and compliance to the hydrocortisone therapy had normal neurodevelopment, while delay in diagnosis and poor compliance was associated with severe hypoglycaemic convulsions and subsequent complications NDD.
Asunto(s)
Insuficiencia Suprarrenal/complicaciones , Epilepsia/etiología , Trastornos del Neurodesarrollo/etiología , Errores Congénitos del Metabolismo Esteroideo/complicaciones , Insuficiencia Suprarrenal/genética , Preescolar , Epilepsia/genética , Femenino , Humanos , Lactante , Masculino , Proteínas de la Membrana/genética , Trastornos del Neurodesarrollo/genética , Receptor de Melanocortina Tipo 2/genética , Errores Congénitos del Metabolismo Esteroideo/genéticaRESUMEN
INTRODUCTION: P450 oxidoreductase (POR) deficiency is a rare form of congenital adrenal hyperplasia. In both genders, it can lead to ambiguous genitalia, impaired steroidogenesis, and skeletal findings similar to those of Antley-Bixler syndrome. CASES: We describe two cases of POR deficiency. The first case was an 8.5-year-old girl who was admitted to our clinic due to ambiguous genitalia. Karyotype was 46, XX. There were mild dysmorphic facial findings and mild metacarpophalangeal joint deformity. The patient's basal cortisol and ACTH levels were normal, while 17-hydroxyprogesterone (17OHP) levels were high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Our second case, a sibling of the first case, was admitted for routine checkup at the age of 15 months. As in our first case, there were dysmorphic facial findings and metacarpophalangeal joint deformity. The genital structure was normal. Karyotype was 46, XY. Basal cortisol and ACTH levels were normal, while 17OHP level was slightly high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Based on our findings, POR deficiency was considered in both of these cases and NM_000941.3:c.929_937delTCTCGGACT(p.Ile310_Ser313delinsThr) (homozygous) mutation was detected in the POR gene that had not previously been described. CONCLUSION: We detected a novel variant in the POR gene in two sibling cases with adrenal insufficiency, dysmorphic face, and mild skeletal findings. While the detected mutation caused ambiguous genitalia in the female case, it did not cause ambiguous genitalia in the male case.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Fenotipo del Síndrome de Antley-Bixler , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Hormona Adrenocorticotrópica , Fenotipo del Síndrome de Antley-Bixler/diagnóstico , Fenotipo del Síndrome de Antley-Bixler/genética , Niño , Femenino , Humanos , Hidrocortisona , Lactante , Masculino , Mutación , Fenotipo , HermanosRESUMEN
BACKGROUND: There are not enough studies investigating the relationship between obesity and ECG abnormalities in children and adolescents. This study aims to investigate the relationship between obesity and electrocardiographic data in children and adolescents for early diagnosis to prevent arrhythmia or sudden death in later stages of life. PATIENTS AND METHODS: A total of 65 children and adolescents with obesity applied to our pediatric endocrinology outpatient clinic with nonspecific complaints and without any known chronic illnesses; 76 healthy children and adolescents were included in the study. Anthropometric and laboratory data, blood pressure measurements, and 12-lead electrocardiography data of all participants were collected. RESULTS: There was a statistically significant difference between the obese and the control group in terms of triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein levels, and systolic blood pressure. According to electrocardiographic findings, there was a statistically significant difference between the two groups in terms of heart rate (p=0.008), PR duration (p<0.001), left ventricular hypertrophy (p=0.02), P maximum (p=0.04), P dispersion (p<0.001), QRS duration (p<0.001), QT minimum (p=0.007), QT maximum (p=0.03), QT dispersion (p=0.024), QTc minimum (p=0.002), QTc dispersion (p=0.003), Tp-e minimum (p=0.007), and Tpe maximum (p=0.003) variables. CONCLUSIONS: There were significant differences between the electrocardiographic evaluation of obese group compared to the control group in our study, which may be associated with risk of cardiac arrhythmia. These differences require monitorization in terms of cardiac arrhythmia and risk of sudden death. Further studies with longer follow-up time are needed to support the potential clinical outcomes of our findings.