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INTRODUCTION: The aim of this study is to evaluate and compare the trabecular bone scores (TBSs) of 11 children and 24 adults with X-linked hypophosphatemic rickets (XLH) and non-XLH subjects from a tertiary center. MATERIALS AND METHODS: The areal bone mineral density at the lumbar spine (LS-aBMD) and LS-aBMD Z score were analyzed by dual-energy X-ray absorptiometry. The bone mineral apparent density (BMAD) and LS-aBMD Z score adjusted for height Z score (LS-aBMD-HAZ) were calculated. The TBS was determined using TBS iNsight software based on DXA images from the Hologic QDR 4500 device. RESULTS: The XLH patients exhibited a higher mean LS-aBMD Z score, BMAD, and TBS than the non-XLH subjects (p < 0.01). LS-aBMD-HAZ and BMAD were greater in the XLH children than those in their corresponding non-XLH subjects (p < 0.01 and p = 0.02), and the XLH children trended toward a greater TBS (p = 0.06). The XLH adults had a higher LS-aBMD Z score, BMAD, and TBS than the non-XLH subjects (p < 0.01). When stratified by metabolic status according to the serum values of bone formation markers, compensated adult patients had a higher LS-aBMD Z score, BMAD, and TBS than non-XLH subjects (p < 0.01). Noncompensated patients had higher LS-aBMD Z scores and BMAD results than non-XLH subjects. However, TBS values did not differ statistically significantly between those groups (p = 0.45). CONCLUSION: The higher LS-aBMD Z score, BMAD, and TBS result in the XLH patients compared to non-XLH subjects indicates an increased amount of trabecular bone within the lumbar spine, regardless of extraskeletal calcifications.
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Hueso Esponjoso , Raquitismo Hipofosfatémico Familiar , Humanos , Adulto , Niño , Hueso Esponjoso/diagnóstico por imagen , Raquitismo Hipofosfatémico Familiar/diagnóstico por imagen , Densidad Ósea , Absorciometría de Fotón/métodos , Vértebras Lumbares/diagnóstico por imagenRESUMEN
Background: Parathyroid carcinoma (PC) is a rare and challenging disease without clearly understood prognostic factors. Adequate management can improve outcomes. Characteristics of patients treated for PC over time and factors affecting prognosis were analyzed. Methods: Retrospective cohort study including surgically treated patients for PC between 2000 and 2021. If malignancy was suspected, free-margin resection was performed. Demographic, clinical, laboratory, surgical, pathological, and follow-up characteristics were assessed. Results: Seventeen patients were included. Mean tumor size was 32.5â mm, with 64.7% staged as pT1/pT2. None had lymph node involvement at admission, and 2 had distant metastases. Parathyroidectomy with ipsilateral thyroidectomy was performed in 82.2%. Mean postoperative calcium levels were different between patients who developed recurrence vs those who did not (P = .03). Six patients (40%) had no recurrence during follow-up, 2 (13.3%) only regional, 3 (20%) only distant, and 4 (26.6%) both regional and distant. At 5 and 10 years, 79% and 56% of patients were alive, respectively. Median disease-free survival was 70 months. Neither Tumor, Nodule, Metastasis system nor largest tumor dimension (P = .29 and P = .74, respectively) were predictive of death. En bloc resection was not superior to other surgical modalities (P = .97). Time between initial treatment and development of recurrence negatively impacted overall survival rate at 36 months (P = .01). Conclusion: Patients with PC can survive for decades and have indolent disease course. Free margins seem to be the most important factor in initial surgery. Recurrence was common (60%), but patients with disease recurrence within 36 months of initial surgery had a lower survival rate.
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CONTEXT: Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VFs). OBJECTIVE: To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers, Wnt inhibitors, bone mineral density (BMD), microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared with healthy control group (HC). DESIGN, SETTING, AND PATIENTS: Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA), and 53 HC. Serum procollagen type 1 N-terminal propeptide, ß-carboxy-terminal crosslinked telopeptide of type 1 collagen, osteocalcin, sclerostin, and DKK1 were measured in blood samples. dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) and vertebral fractures evaluation were also assessed simultaneously. MAIN OUTCOME AND RESULTS: AcroA showed significantly lower sclerostin and higher DKK1 compared with HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity, and increased cortical area and cortical thickness compared with HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (Râ =â 0.45, Pâ =â 0.044). Mild VFs were present in approximately 30% of patients. CONCLUSIONS: Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure, and increased VF. Sclerostin was not correlated with any HR-pQCT parameters; however, DKK1 was correlated with cortical porosity in tibia (Pâ =â 0.027). Additional studies are needed to clarify the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.
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Acromegalia/patología , Huesos/ultraestructura , Vía de Señalización Wnt/fisiología , Adulto , Densidad Ósea , Huesos/metabolismo , Estudios Transversales , Femenino , Análisis de Elementos Finitos , Humanos , Péptidos y Proteínas de Señalización Intercelular/sangre , Persona de Mediana Edad , Premenopausia , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiologíaRESUMEN
BACKGROUND: In kidney transplant patients, parathyroidectomy is associated with an acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been extensively studied in primary hyperparathyroidism (PHPT). METHODS: This retrospective cohort study included 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post-parathyroidectomy and were stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up. RESULTS: A total of 391 (79.1%) patients were female, and 422 (85.4%) were non-African American. The median age was 58 years old. The median (first and third quartiles) preoperative serum creatinine, PTH and total calcium levels were 0.81 mg/dL (0.68-1.01), 154.5 pg/mL (106-238.5), and 10.9 mg/dL (10.3-11.5), respectively. The median (first and third quartiles) preoperative eGFR was 86 mL/min/1.73 m2 (65-101.3). After surgery, the median acute decrease in the eGFR was 21 mL/min/1.73 m2 (p<0.0001). Acutely, 41.1% of patients developed stage 1 AKI, 5.9% developed stage 2 AKI, and 1.8% developed stage 3 AKI. The acute eGFR decrease (%) was correlated with age and PTH, calcium and preoperative creatinine levels in univariate analysis. Multivariate analysis showed that the acute change was related to age and preoperative values of ionized calcium, phosphorus and creatinine. The change at 12 months was related to sex, preoperative creatinine and 25OHD. Permanent reduction in the eGFR occurred in 60.7% of patients after an acute episode. CONCLUSION: There was significant acute impairment in renal function after parathyroidectomy for PHPT, and almost half of the patients met the criteria for AKI. Significant eGFR recovery was observed during the first month after surgery, but a small permanent reduction may occur. Patients treated for PHPT seemed to present with prominent renal dysfunction compared to patients who underwent thyroidectomy.
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Lesión Renal Aguda/epidemiología , Hiperparatiroidismo Primario/cirugía , Paratiroidectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Lesión Renal Aguda/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
CONTEXT: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. OBJECTIVE: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder. DESIGN: Screening by karyotype (n = 42), chromosome microarray analyses (CMA) (n = 16), MS-MLPA (n = 2) targeted panel (n = 12) and whole-exome sequencing (n = 31). PATIENTS AND METHODS: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic (n = 30) and non-syndromic (n = 12) subgroups. MAIN OUTCOME MEASURES: Frequencies of pathogenic findings. RESULTS: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith-Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques (FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients. CONCLUSION: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup.
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Gigantismo/genética , Trastornos del Crecimiento/genética , Adolescente , Adulto , Estatura/genética , Niño , Preescolar , Variaciones en el Número de Copia de ADN/genética , Heterocigoto , Humanos , Cariotipo , Cariotipificación , Persona de Mediana Edad , Estudios Prospectivos , Proteína de la Caja Homeótica de Baja Estatura/genética , Secuenciación del Exoma/métodos , Adulto JovenRESUMEN
Context: Five different activating PTH/PTH-related peptide (PTHrP) receptor (PTHR1) mutations have been reported as causes of Jansen metaphyseal chondrodysplasia (JMC), a rare disorder characterized by severe growth plate abnormalities and PTH-independent hypercalcemia. Objectives: Assess the natural history of clinical and laboratory findings in 24 patients with JMC and characterize the disease-causing mutant receptors in vitro. Patients and Methods: The H223R mutation occurred in 18 patients. T410P, I458R and I458K each occurred in single cases; T410R was present in a father and his two sons. Laboratory records were analyzed individually and in aggregate. Results: Postnatal calcium levels were normal in most patients, but elevated between 0.15 and 10 years (11.8 ± 1.37 mg/dL) and tended to normalize in adults (10.0 ± 1.03 mg/dL). Mean phosphate levels were at the lower end of the age-specific normal ranges. Urinary calcium/creatinine (mg/mg) were consistently elevated (children, 0.80 ± 0.40; adults, 0.28 ± 0.19). Adult heights were well below the 3rd percentile for all patients, except for those with the T410R mutation. Most patients with JMC had undergone orthopedic surgical procedures, most had nephrocalcinosis, and two had advanced chronic kidney disease. The five PTHR1 mutants showed varying degrees of constitutive and PTH-stimulated cAMP signaling activity when expressed in HEK293 reporter cells. The inverse agonist [L11,dW12,W23,Y36]PTHrP(7-36) reduced basal cAMP signaling for each PTHR1 mutant. Conclusions: Except for T410R, the other PTHR1 mutations were associated with indistinguishable mineral ion abnormalities and cause similarly severe growth impairment. Hypercalciuria persisted into adulthood. An inverse agonist ligand effectively reduced in vitro PTH-independent cAMP formation at all five PTHR1 mutants, suggesting a potential path toward therapy.
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Biomineralización/genética , Mutación/genética , Osteocondrodisplasias/genética , Proteína Relacionada con la Hormona Paratiroidea/genética , Receptor de Hormona Paratiroídea Tipo 1/genética , Adulto , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To describe the oral and maxillofacial manifestations of patients diagnosed with chronic kidney disease-mineral and bone disorders. STUDY DESIGN: Over a 13-year period, clinicopathologic data of patients diagnosed with CKD-MBD who had oral and maxillofacial alterations were retrieved from the files of 4 Brazilian institutions. Data included clinical, radiographic, microscopic, and biochemical findings; treatment employed; and follow-up status. RESULTS: Twenty-one cases were identified, with 13 patients diagnosed as brown tumor of hyperparathyroidism (BTH) and 8 as osteitis fibrosa/renal osteodystrophy (OF/RO) (4 of them clinically consistent with Sagliker syndrome). The mean age was 32.7 years, and the mandible was the most affected site (42.8%). OF/RO had an ill-defined "ground glass" radiographic appearance, and BTH produced well-defined radiolucent images. Biochemically the following mean values were obtained: parathormone 1511.07 pg/mL, calcium 9.25 mg/dL, phosphorus 5.19 mg/dL, alkaline phosphatase 941.55 U/L, urea 125.42 mg/dL, and creatinine 7.14 mg/dL. Treatment comprised vitamin D and calcium intake, parathyroidectomy, hemodialysis, renal transplantation, and local surgery. During follow-up, 5 patients with BTH were free of lesions, whereas 2 affected by OF/RO/Sagliker syndrome died. CONCLUSIONS: Oral and maxillofacial manifestations of BTH and OF/RO are uncommon, but they can be associated with an important life-threatening scenario.
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Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/complicaciones , Enfermedades de la Boca/etiología , Adolescente , Adulto , Anciano , Brasil , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Pseudohypoparathyroidism (PHP) is a genetic disorder characterized by resistance to the peripheral action of PTH due to maternally inherited heterozygous inactivating mutations in the coding sequence of Gsα or intronic regions of GNAS leading to aberrant splice variants (PHP1A), or methylation defects at GNAS (PHP1B). Brachydactyly is a clinical feature associated with both PHP1A and PHP1B, although it is more frequent in PHP1A patients. Loss-of-function mutations in PTHLH, the gene coding for parathyroid hormone related protein (PTHrP) were previously described in some patients with brachydactyly. Primary failure of tooth eruption (PFE) is related to some syndromes involving skeletal development, but it is also known as a nonsyndromic autosomal dominant condition. Previous studies showed that familial nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor (PTH1R) for PTH and PTHrP. Thus, we hypothesized that PTHrP resistance could result in failure of tooth eruption (FTE) and/or brachydactyly in PHP. SUBJECTS AND METHODS: Nineteen patients with a molecular diagnosis of PHP underwent dental panoramic radiography (DPR), hand radiography and had their PTHrP levels measured. Patients with alterations at DPR were submitted to clinical dental evaluation. RESULTS: Nine patients had FTE and 7 patients had brachydactyly; 4 patients presented both features and none of them presented high PTHrP levels. Fourteen patients had PTHrP levels within the normal range and only one patient had slightly elevated PTHrP levels. Additionally, three novel GNAS mutations were described. CONCLUSION: We described the dental abnormalities in a large series of PHP patients that were followed in a single tertiary center. No relationship between plasma PTHrP levels and failure of tooth eruption, dental manifestations of PHP or brachydactyly was found. It is important that doctors pay attention to dental manifestations of the disease in order to refer patients to a proper care with dentists.
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Braquidactilia/sangre , Braquidactilia/complicaciones , Proteína Relacionada con la Hormona Paratiroidea/sangre , Seudohipoparatiroidismo/sangre , Seudohipoparatiroidismo/complicaciones , Erupción Dental , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENT(S): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. RESULT(S): Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. CONCLUSION(S): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.
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Trastornos del Desarrollo Sexual 46, XX/genética , Corticoesteroides , Hiperplasia Suprarrenal Congénita/genética , Enfermedades del Ovario/genética , Esteroide 17-alfa-Hidroxilasa/genética , Trastornos del Desarrollo Sexual 46, XX/sangre , Trastornos del Desarrollo Sexual 46, XX/diagnóstico , Adolescente , Corticoesteroides/sangre , Hiperplasia Suprarrenal Congénita/sangre , Hiperplasia Suprarrenal Congénita/diagnóstico , Adulto , Niño , Femenino , Humanos , Enfermedades del Ovario/sangre , Enfermedades del Ovario/diagnóstico , Linaje , Estudios Retrospectivos , Adulto JovenAsunto(s)
Neoplasias/diagnóstico por imagen , Octreótido/análogos & derivados , Osteomalacia/diagnóstico por imagen , Tecnecio Tc 99m Sestamibi , Imagen de Cuerpo Entero/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/normas , Neoplasias/complicaciones , Osteomalacia/etiología , Síndromes Paraneoplásicos/diagnóstico por imagen , Cintigrafía , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
PURPOSE: Tumor-induced osteomalacia (TIO) is a paraneoplastic bone mineral disturbance related to fibroblast growth factor 23 (FGF23) overproduction by the tumor, usually from mesenchymal origin. Such condition leads to high phosphate renal wasting and, consequently, to cumbersome symptoms as weakness, bone pain, and fractures. METHOD: Case report. RESULT: We report a case of an advanced castration-refractory prostate cancer patient, which developed severe hypophosphatemia with elevated phosphate excretion fraction. TIO was suspected, and increased levels of FGF23 reinforced such diagnosis. The patient died 4 months after being diagnosed with TIO. CONCLUSION: This case suggests that TIO has a dismal prognosis in prostate cancer patients. The clinical oncology community must be aware about such disturbance that can be present in those patients with weakness, bone pain, and hypophosphatemia.
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Neoplasias de Tejido Conjuntivo/etiología , Neoplasias de Tejido Conjuntivo/secundario , Neoplasias de la Próstata/complicaciones , Brasil , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Hipofosfatemia/sangre , Masculino , Persona de Mediana Edad , Neoplasias de Tejido Conjuntivo/diagnóstico , Osteomalacia , Síndromes Paraneoplásicos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patologíaAsunto(s)
Enfermedad de Graves/complicaciones , Hiperplasia del Timo/etiología , Adulto , Humanos , MasculinoRESUMEN
WT1 mutations have been described in a variety of syndromes, including Denys-Drash syndrome (DDS), which is characterized by predisposition to Wilms' tumor, genital abnormalities and development of early nephropathy. The most frequent WT1 defects in DDS are missense mutations located in exons 8-9. Our aim is to report a novel WT1 mutation in a 46,XY patient with a DDS variant, who presented a mild nephropathy with a late onset diagnosed during adolescence. He had ambiguous genitalia at birth. At 4 months of age he underwent nephrectomy (Wilms' tumor) followed by chemotherapy. Ambiguous genitalia were corrected and bilateral gonadectomy was performed. Sequencing of WT1 identified a novel heterozygous mutation (c.742A>T) in exon 4 that generates a premature stop codon (p.K248X). Interestingly, this patient has an unusual DDS nephropathy progression, which reinforces that patients carrying WT1 mutations should have the renal function carefully monitored due to the possibility of late-onset nephropathy.
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Codón sin Sentido , Síndrome de Denys-Drash/genética , Genes del Tumor de Wilms , Enfermedades Renales/genética , Proteínas WT1/genética , Secuencia de Bases , Síndrome de Denys-Drash/etiología , Síndrome de Denys-Drash/patología , Heterocigoto , Humanos , Lactante , Recién Nacido , Enfermedades Renales/complicaciones , Masculino , Tumor de Wilms/genética , Adulto JovenRESUMEN
A loss of calcium-sensing receptor (CASR) function due to inactivating mutations can cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). NSHPT represents the most severe expression of FHH and courses as a life-threatening condition. The aim of this study was to identify and characterize a CASR mutation in a female infant brought to the health service due to dehydration, apathy, lack of breast feeding and severe hypercalcemia. Molecular analysis was performed on genomic DNA of the index case and her parents. A novel homozygous mutation (p.E519X) in CASR was identified in the proband; both mother and father had the same mutation in heterozygous state, confirming their FHH condition. The mutation results in a truncated and inactive protein due to the lack of transmembrane and intracellular domains. The identification of this novel CASR gene mutation established the basis of hypercalcemia in this family and allowed a genetic counseling.
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Hipercalcemia/congénito , Hiperparatiroidismo/genética , Mutación/genética , Receptores Sensibles al Calcio/genética , Femenino , Humanos , Hipercalcemia/sangre , Hipercalcemia/genética , Hiperparatiroidismo/cirugía , Lactante , Recién Nacido , Linaje , RecurrenciaRESUMEN
A loss of calcium-sensing receptor (CASR) function due to inactivating mutations can cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). NSHPT represents the most severe expression of FHH and courses as a life-threatening condition. The aim of this study was to identify and characterize a CASR mutation in a female infant brought to the health service due to dehydration, apathy, lack of breast feeding and severe hypercalcemia. Molecular analysis was performed on genomic DNA of the index case and her parents. A novel homozygous mutation (p.E519X) in CASR was identified in the proband; both mother and father had the same mutation in heterozygous state, confirming their FHH condition. The mutation results in a truncated and inactive protein due to the lack of transmembrane and intracellular domains. The identification of this novel CASR gene mutation established the basis of hypercalcemia in this family and allowed a genetic counseling.
Mutações inativadoras no gene do sensor do cálcio (CASR) podem causar hipercalcemia hipocalciúrica familiar (HHF) ou hiperparatireoidismo neonatal grave (HPTNSG). A HPTNS representa a forma mais grave da HHF cursando com risco de vida. O objetivo deste estudo foi identificar e caracterizar uma mutação no gene CASR de uma criança do sexo feminino levada ao hospital em decorrência de desidratação, apatia, dificuldade para mamar e hipercalcemia grave. A análise molecular foi realizada a partir do DNA genômico do caso índice e de seus pais. Uma nova mutação em homozigose (p.E519X) foi identificada no caso índice; ambos, mãe e pai, apresentaram a mesma mutação em heterozigose, o que os caracteriza como portadores de HHF. Essa alteração resulta em uma proteína truncada e inativa devido à falta dos domínios transmembrana e intracelular. A identificação dessa nova mutação estabeleceu a causa da hipercalcemia na família e permitiu o aconselhamento genético.
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Femenino , Humanos , Lactante , Recién Nacido , Hipercalcemia/congénito , Hiperparatiroidismo/genética , Mutación/genética , Receptores Sensibles al Calcio/genética , Hipercalcemia/sangre , Hipercalcemia/genética , Hiperparatiroidismo/cirugía , Linaje , RecurrenciaAsunto(s)
Adulto , Humanos , Masculino , Enfermedad de Graves/complicaciones , Hiperplasia del Timo/etiologíaRESUMEN
The objective of this study was to describe a new mutation in GNAS in a family with pseudohypoparathyroidism type Ia (PHP Ia), a rare osteometabolic disease. An 8-month-old boy was seen by an Endocrinologist due to obesity and low growth velocity. Noteworthy, his mother exhibited typical Albright hereditary osteodystrophy (AHO) phenotype. The clinical diagnosis of PHP Ia was suspected. The GNAS coding region from mother and son was amplified and directly sequenced. A novel heterozygous missense mutation (c.673T>C) was identified in exon 5 in both patients. In this family, the mother's clinical picture was the clue for the son's diagnosis. Molecular analysis of GNAS confirmed the diagnosis of PHP Ia in both patients and the child's early diagnosis was possible. Moreover, this novel missense substitution expands the spectrum of GNAS mutations associated with this disorder and allows for genetic counseling of this family.
O objetivo deste estudo foi descrever uma nova mutação no GNAS em uma família com pseudo-hipoparatireoidismo tipo Ia (PHP Ia), doença osteometabólica rara. Um garoto de oito meses foi visto por um endocrinologista por obesidade e baixa velocidade de crescimento. Chamava a atenção o fato de sua mãe apresentar fenótipo típico da osteodistrofia hereditária de Albright (OHA). O diagnóstico clínico de PHP Ia foi suspeitado. A região codificadora do GNAS da mãe e do filho foi amplificada e submetida ao sequenciamento direto. Uma nova mutação missense em heterozigose (c.673T>C) foi identificada no éxon 5 em ambos. O quadro clínico materno foi a pista para o diagnóstico do filho. A análise molecular do GNAS confirmou o diagnóstico de PHP Ia nos dois pacientes possibilitando o diagnóstico precoce da criança. Além disso, essa nova substituição missense expande o espectro de mutações no GNAS associadas a essa doença e permite o aconselhamento genético nesta família.
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Femenino , Humanos , Lactante , Masculino , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Mutación Missense/genética , Seudohipoparatiroidismo/genética , Calcio/sangre , Diagnóstico Precoz , Madres , Hormona Paratiroidea/sangre , Fosfatos/sangre , Seudohipoparatiroidismo/sangre , Valores de ReferenciaRESUMEN
Introdução: Após paratireoidectomia por hiperparatireoidismo primário, alguns pacientes apresentam redução transitória da função renal. O mecanismo dessa alteração ainda é incerto. Objetivo: Analisar se a função renal pré-operatória está relacionada à alteração da taxa de filtração glomerular após paratireoidectomia. Casuística e Método: Em pacientes submetidos a tratamento cirúrgico por hiperparatireoidismo primário a taxa de filtração glomerular (eGFR) foi estimada a partir dos valores da creatinina antes e até 48 horas após a operação. As variações foram comparadas em doentes com doença renal pré-operatória severa/moderada, leve e função normal. Resultados: Em 52 casos havia valores passíveis de análise, sendo 43 mulheres. A média de idade foi 56,4 anos. A eGFR pré-operatória foi de 83 mL/min/1,73m2 e a média pós-operatória foi de 63 mL/min/1,73m2 (p<0,0001). Nos pacientes com Doença Renal Severa/Moderada a eGFR reduziu-se em 21,8%. A redução nos pacientes com Doença Renal Leve foi de 30,3% e nos casos com função renal pré-operatória normal houve decréscimo de 21,8%. (p=0,35) Não houve correlação significativa entre a função renal pré-operatória e queda da eGFR no pós-operatório (R2 =0,0038; p=0,66). Em 47 casos observou-se alguma redução da eGFR, que variou entre - 1 mL/min/1,73m2 a - 140 mL/min/1,73m2. Conclusão: Após paratireoidectomia há uma redução da eGFR. Não há relação do percentual de variação de acordo com a situação renal de base.
Introduction: After successful parathyroidectomy for primary hyperparathyroidism, some patients present a transient reduction of renal function. The mechanism for this change is uncertain. Objective: To evaluate if preoperative renal function correlates with the degree of estimated glomerular filtration rate (eGFR) change after parathyroidectomy. Patients and Method: In patients submitted to surgical treatment of primary hyperparathyroidism, the eGFR was determined from creatinine levels before and until 48 hours after the operation. Changes were compared according to a stratified renal function as follows: severe and moderate, mild and normal renal function. Results: In 52 cases there were available measures of creatinine to evaluate eGFR. Of these, 43 were women. Mean age was 56.4 years. The preoperative eGFR was 83 mL/min/1.73m2 and the postoperative mean was 63 mL/min/1.73m2 (p<0.0001). In patients with severe or moderate kidney disease, the EGFR reduction was of 21.8%. The reduction in patients with mild renal disease was of 30.3% and in patients with preoperative normal renal function a transient decrease of 21.8% was observed (p=0.35) There was not a significant correlation between preoperative renal function and the mean decrease of eGFR during postoperative period (R2 =0.0038; p=0.66). In 47 cases some reduction of eGFR was observed, ranging from - 140 mL/min/1.73m2 to -1 mL/min/1.73m2. Conclusion: After parathyroidectomy there is a significant reduction of eGFR. There is no correlation between the previous renal function and the relative change of renal function.
RESUMEN
Although BMD measured by DXA is a useful clinical tool for osteoporosis diagnosis, changes resulting from osteoporosis treatment only partially explain the observed reduction in fractures. Several other bone properties that influence its resistance to fractures and explain this discrepancy have been defined as "bone quality". Bone quality is determined by its structural and material properties and orchestrated by bone turnover, a continuous process of renewal through which old or damaged bone is replaced by a mechanically healthy bone and calcium homeostasis is maintained. Bone structural properties include its geometry (size and shape) and microarchitecture (trabecular architecture and cortical porosity), while bone material properties include its mineral and collagen composition as well as microdamage and its repair. This review aims to update concepts surrounding bone quality and how drugs employed to treat osteoporosis might influence them.