X-linked hypophosphatemic rickets: Description of seven new variants in patients followed up in reference hospitals in Rio de Janeiro.

BACKGROUND: X-linked hypophosphatemic rickets (XLHR) is a rare genetic disease, often delayed in diagnosis due to the low degree of suspicion and limited access to sophisticated diagnostic tools that confirm the diagnosis, such as genetic testing. METHODS: Through a cross-sectional and observational study, 26 patients with a previously presumptive diagnosis of X-linked hypophosphatemic rickets (based on clinical history, laboratory findings, and physical examination), were followed for approximately 12 months. During 12 months of follow-up, only 16 patients underwent genetic testing and enrolled in the study. Previous data were analyzed, such as clinical history (e.g., gender, current age, age of clinical diagnosis, age of admission to hospital, family history, and previous orthopedic surgery), physical exam, imaging tests (e.g., radiological changes) and laboratory tests (e.g., tubular maximum reabsorption rate of phosphate to glomerular filtration rate, alkaline phosphatase, and phosphate levels) at the time of the patient's admission to IEDE and UFRJ, to corroborate and substantiate our research. These data were extracted from the medical records of the patients. RESULTS: Among the 16 patients analyzed by molecular biology techniques, the new generation sequencing (NGS), using DNA samples from oral swabs, we obtained seven variants never previously described, which were verified by Sanger sequencing. Among the seven variants never previously described, the most common coding impact was the nonsense mutation. We found two frameshift, one intronic splicing variant, three nonsense, and one deletion splice junction loss. Among patients with new mutations who presented data in the medical record, 100% showed a reduction in TmP/GFR (average of 1.98 mg/dl), the most sensitive laboratory parameter at the time of diagnosis, as well as serum phosphorus (100% had hypophosphatemia on arrival at the referral hospitals--average of 2.4 mg/dl and median 2.3 mg/dl). We also performed NGS on three mothers of the patients with identified mutations. Among these mothers, only one tested negative for the mutation and no family history was reported as well. This mother had serum phosphate of 3.5 mg/dl (normal range: 2.5-4.5 mg/dl) at the time of genetic test collection. The others had a positive test, low serum phosphorus at the time of the molecular test, in addition to a positive family history. CONCLUSION: This study describes seven new variants in the PHEX gene and aims to increase the knowledge of the scientific community about the types of mutations involving this gene, increasing information on the genetic basis of this condition, enabling future considerations about genotype-phenotype correlation, in addition to diagnosis accurate and early.

ROLE OF IMAGING TESTS FOR PREOPERATIVE LOCATION OF PATHOLOGIC PARATHYROID TISSUE IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: Primary hyperparathyroidism (PHPT) can be cured by parathyroidectomy, and the preoperative location of enlarged pathologic parathyroid glands is determined by imaging studies, especially cervical ultrasonography and scintigraphy scanning. The aim of this retrospective study was to evaluate the use of preoperative cervical ultrasonography and/or parathyroid scintigraphy in locating pathologic parathyroid tissue in a group of patients with PHPT followed in the same endocrine center. METHODS: We examined the records of 61 patients who had undergone parathyroidectomy for PHPT following (99m)Tc-sestamibi scintigraphy scan and/or cervical ultrasonography. Scintigraphic and ultrasonographic findings were compared to histopathologic results of the surgical specimens. RESULTS: Ultrasonography detected enlarged parathyroid glands in 87% (48/55) of patients with PHPT and (99m)Tc-sestamibi scintigraphy in 79% (37/47) of the cases. Ultrasonography was able to correctly predict the surgical findings in 75% (41/55) of patients and scintigraphy in 72% (34/47). Of 7 patients who had negative ultrasonography, scintigraphy correctly predicted the surgical results in 2 (29%). Of 10 patients who had negative scintigraphy, ultrasonography correctly predicted the surgical results in 4 (40%). When we analyzed only patients with solitary eutopic parathyroid adenomas, the predictive positive values of ultrasonography and scintigraphy were 90% and 86%, respectively. CONCLUSION: Cervical ultrasonography had a higher likelihood of a correct positive test and a greater predictive positive value for solitary adenoma compared to (99m)Tc-sestamibi and should be used as the first diagnostic tool for preoperative localization of affected parathyroid glands in PHPT. ABBREVIATIONS: Ca = calcium IEDE = Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione PHPT = primary hyperparathyroidism PTH = parathyroid hormone.

Hiperparatireoidismo primário familiar isolado: análise e descrição de uma família com seis casos índices: [carta ao editor] / Familial isolated primary hyperparathyroidism: description and analyses of six cases: [letter to the editor]

Objetivamos descrever e analisar uma família com seis casos de hiperparatireoidismo familiar isolado (HFI), uma rara doença hereditária de padrão autossômico dominante, caracterizada por hiperparatireoidismo primário sem associação com outras doenças ou tumores endocrinológicos. O diagnóstico foi realizado através da demonstração de hipercalcemia, aumento dos níveis de paratormônio e tumores de paratireóide à histopatologia, excluindo-se neoplasias endócrinas múltiplas do tipo 1 (NEM 1) e do tipo 2a (NEM 2a), além da síndrome hiperparatireoidismo/tumor de mandíbula (HPT/TM). Analisamos a descrição dos exames diagnósticos iniciais, a abordagem cirúrgica, os laudos histopatológicos pós-operatórios e suas evoluções. A primeira paciente operada neste instituto há 20 anos, recidivou onze anos após, e possuía uma irmã com diagnóstico prévio, o que motivou a investigação de outros familiares. A observação do caráter familial nesses pacientes contribuiu para a facilitação diagnóstica e encaminhamento terapêutico dos mesmos, assim como a orientação clínica e genética à família.

Our objective is to evaluate and describe one family with six cases of familial isolated primary hyperparathyroidism (HFI), a rare hereditable disorder with an autossomal dominant mode of inheritance. It is characterized by a primary hyperparathyroidism without association with other endocrine tumors or diseases. The HFI diagnosis relied on the demonstration of hypercalcemia, inappropriately high levels of parathyroid hormone, and parathyroid adenomas, plus exclusion of NEM 1/2a and HPT/TM syndrome in this family. We analyzed the description of the first diagnosis, surgical approach, postoperative histopathological results and their development process. The first patient, treated in our institute twenty years ago, has recidivated eleven years after the treatment. Her sister had had the same diagnosis, which motivated us to investigate theirs relatives. The analysis of the characteristics that run in these patients' family has contributed to facilitate their diagnosis and therapeutic treatment, including clinical and genetic orientation of this family.

[Familial isolated primary hyperparathyroidism--description and analyses of six cases]. / Hiperparatireoidismo primário familiar isolado--análise e descrição de uma família com seis casos índices.

Our objective is to evaluate and describe one family with six cases of familial isolated primary hyperparathyroidism (HFI), a rare hereditable disorder with an autossomal dominant mode of inheritance. It is characterized by a primary hyperparathyroidism without association with other endocrine tumors or diseases. The HFI diagnosis relied on the demonstration of hypercalcemia, inappropriately high levels of parathyroid hormone, and parathyroid adenomas, plus exclusion of NEM 1/2a and HPT/TM syndrome in this family. We analyzed the description of the first diagnosis, surgical approach, postoperative histopathological results and their development process. The first patient, treated in our institute twenty years ago, has recidivated eleven years after the treatment. Her sister had had the same diagnosis, which motivated us to investigate theirs relatives. The analysis of the characteristics that run in these patients' family has contributed to facilitate their diagnosis and therapeutic treatment, including clinical and genetic orientation of this family.