RESUMO
INTRODUCTION: Phosphaturic mesenchymal tumor mixed connective tissue type (PMT/MCT) is the most common type (up to 90%) of phosphaturic mesenchymal tumor (PMT), a rare clinicopathologic entity. Besides overproduction of fibroblast growth factor 23 (FGF23), there is a big variation of immunohistochemical characteristic across types of PMT, which makes it difficult to obtain an early diagnosis of PMT/MCT. As a benign tumor, PMT/MCT usually happens in subcutaneous tissues and leads to nonhealing of wound. A complete excision of PMT/MCT facilitates wound healing. CONCLUSIONS: Review of the existing evidence indicates that early diagnosis of PMT/MCT is critically important when treating PMT/MCT wound. Hence standardization of early diagnosis for PMT/MCT is mandated.
Assuntos
Hipofosfatemia Familiar/diagnóstico , Mesenquimoma/diagnóstico , Doença Mista do Tecido Conjuntivo/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Ferimentos e Lesões/complicações , Biomarcadores Tumorais/sangue , Diagnóstico Diferencial , Detecção Precoce de Câncer , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/biossíntese , Humanos , Hipofosfatemia Familiar/sangue , Hipofosfatemia Familiar/etiologia , Mesenquimoma/sangue , Mesenquimoma/etiologia , Doença Mista do Tecido Conjuntivo/sangue , Doença Mista do Tecido Conjuntivo/etiologia , Neoplasias de Tecidos Moles/sangue , Neoplasias de Tecidos Moles/etiologia , Ferimentos e Lesões/sangueAssuntos
Hipofosfatemia Familiar/complicações , Mesenquimoma/diagnóstico por imagem , Osteomalacia/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Diagnóstico Diferencial , Humanos , Hipofosfatemia Familiar/diagnóstico , Masculino , Mesenquimoma/patologia , Pessoa de Meia-Idade , Osteomalacia/patologia , Medição de Risco , Neoplasias de Tecidos Moles/patologia , Coxa da PernaAssuntos
Doença de Crohn/cirurgia , Fraturas do Colo Femoral/etiologia , Compostos Férricos/efeitos adversos , Hematínicos/efeitos adversos , Hipofosfatemia Familiar/induzido quimicamente , Hipofosfatemia/induzido quimicamente , Maltose/análogos & derivados , Osteomalacia/induzido quimicamente , Hemorragia Pós-Operatória/tratamento farmacológico , Administração Intravenosa , Anti-Inflamatórios/uso terapêutico , Biópsia , Doença de Crohn/diagnóstico , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Quimioterapia Combinada , Fraturas do Colo Femoral/diagnóstico por imagem , Compostos Férricos/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Hematínicos/administração & dosagem , Humanos , Hipofosfatemia/diagnóstico , Hipofosfatemia Familiar/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Maltose/administração & dosagem , Maltose/efeitos adversos , Pessoa de Meia-Idade , Osteomalacia/diagnóstico , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/etiologiaRESUMO
INTRODUCTION: Osteomalacia is associated with diffuse pain and multiple fractures and therefore, diagnosis and treatment of this condition are necessary. Clinicians should be aware of an uncommon mechanism of osteomalacia where hypophosphataemia is secondary to renal phosphaturia because of the production by a mesenchymal phosphaturic tumor of FGF-23. This tumor should be localized and removed to cure this tumor-induced osteomalacia. OBSERVATION: A 70-year-old female patient was admitted to explore diffuse pain caused by multiple fractures secondary to osteomalacia. Despite vitamin D supplementation, she remained profoundly hypophosphoremic with major renal phosphaturia. A tumor-induced mechanism was suspected because of high level of FGF-23. It took more than three years of investigation to spot the causal phosphaturic mesenchymal tumor despite annual repetition of indium-labelled scintigraphy and PET-scan. The resection of the tumor, located between two phalanges of the right foot, cured the patient with sustained normal rate of serum level of phosphorus after two years. CONCLUSION: Tumor-induced osteomalacia is a diagnostic challenge because the localization of the tumor may be a long process. Patients should be monitored clinically and imaging studies repeated until a diagnosis is made and the causal tumor removed.
Assuntos
Hipofosfatemia Familiar/etiologia , Mesenquimoma/complicações , Neoplasias de Tecido Conjuntivo/etiologia , Neoplasias de Tecidos Moles/complicações , Idoso , Diagnóstico Tardio , Feminino , Fator de Crescimento de Fibroblastos 23 , Pé , Humanos , Hipofosfatemia/complicações , Hipofosfatemia Familiar/diagnóstico , Mesenquimoma/diagnóstico , Neoplasias de Tecido Conjuntivo/diagnóstico , Osteomalacia , Síndromes Paraneoplásicas , Neoplasias de Tecidos Moles/diagnósticoRESUMO
HYPOTHESIS: Phosphorus and vitamin D (calcitriol) supplementation in the Phex mouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). BACKGROUND: Male Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice's postnatal development of ELH and SNHL. METHODS: Four cohorts were studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7-P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. RESULTS: Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. CONCLUSION: Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.
Assuntos
Doenças Ósseas/terapia , Suplementos Nutricionais , Otopatias/terapia , Perda Auditiva Neurossensorial/terapia , Hipofosfatemia Familiar/terapia , Análise de Variância , Animais , Biópsia por Agulha , Doenças Ósseas/diagnóstico , Calcitriol/farmacologia , Modelos Animais de Doenças , Otopatias/diagnóstico , Hidropisia Endolinfática/diagnóstico , Hidropisia Endolinfática/terapia , Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Hipofosfatemia Familiar/diagnóstico , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Fósforo/farmacologia , Distribuição Aleatória , Resultado do TratamentoAssuntos
Vértebras Cervicais , Hipofosfatemia Familiar/complicações , Mesenquimoma/complicações , Neoplasias de Tecido Conjuntivo/etiologia , Neoplasias da Coluna Vertebral/complicações , Idoso , Biópsia , Humanos , Hipofosfatemia Familiar/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Mesenquimoma/diagnóstico , Neoplasias de Tecido Conjuntivo/diagnóstico , Osteomalacia , Síndromes Paraneoplásicas , Fósforo/sangue , Tomografia por Emissão de Pósitrons , Neoplasias da Coluna Vertebral/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
CONTEXT: We report a case of tumor-induced osteomalacia with evidence of synchronous multifocal fibroblast growth factor 23 (FGF23) production. OBJECTIVE: The aim is to present a case of tumor-induced osteomalacia and to highlight the fact that incomplete removal of multifocal FGF23-producing tumors, which are not entirely picked up by functional imaging, could be the cause of treatment failure. SETTING: The patient was treated in the Department of Endocrinology of a tertiary care center in India. PATIENT: We report the case of a 42-year-old male with tumor-induced osteomalacia. INTERVENTION: We treated the tumor-induced osteomalacia with staged surgery of the two tumors. The 18F-fluorodeoxyglucose (FDG)-avid lesion (considered the sole culprit lesion after functional imaging) was resected first, followed by the non-FDG-avid lesion. The sequential removal of both tumors resulted in complete cure. RESULTS: The patient had hypophosphatemia and hyperphosphaturia. C-Terminal FGF23 level was elevated. Positron emission tomography-computed tomography showed two lesions-an FDG-avid lesion in the right leg, and a non-avid lesion in the left thigh. After removal of the FDG-avid lesion, the hypophosphatemia persisted, and the FGF23 level showed only modest reduction. The patient had complete clinical and biochemical resolution only after removal of the second non-FDG-avid tumor. CONCLUSIONS: We present the case of a tumor-induced osteomalacia whose biochemical parameters did not improve after removal of the FDG-avid tumor initially. The possibility of multifocal FGF23 production was considered, and the second, non-FDG-avid lesion was resected, which resulted in complete cure. Thorough clinical examination and meticulous follow-up with documentation of the biochemical resolution are necessary for management of all patients with this rare disorder.
Assuntos
Hipofosfatemia Familiar/diagnóstico , Hipofosfatemia/diagnóstico , Neoplasias de Tecido Conjuntivo/diagnóstico , Adulto , Fator de Crescimento de Fibroblastos 23 , Humanos , Hipofosfatemia/sangue , Hipofosfatemia/cirurgia , Hipofosfatemia Familiar/sangue , Hipofosfatemia Familiar/cirurgia , Índia , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/sangue , Neoplasias de Tecido Conjuntivo/cirurgia , Osteomalacia , Síndromes ParaneoplásicasRESUMO
Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome associated with tumors that secrete phosphaturic hormones, most notably fibroblast growth factor 23 (FGF23). The majority of tumors associated with this syndrome show stereotypical histological features and are now known as phosphaturic mesenchymal tumors (PMTs). We postulated that immunohistochemistry for somatostatin receptor 2A (SSTR2A) could be used to definitively identify PMTs or other tumors that cause TIO. Immunohistochemistry for FGF23 and SSTR2A was performed on 15 tumors from 14 patients with a definite diagnosis of TIO. All showed positive staining for both markers. While FGF23 staining was quite focal in some tumors, SSTR2A showed diffuse strong expression. In 40 control tumors not known to be associated with the clinical or biochemical features of TIO, FGF23 expression was found in 2 cases (one aneurysmal bone cyst and one osteosarcoma). SSTR2A expression was found in 9 control tumors (4 synovial sarcomas, 2 hemangiomas, 2 aneurysmal bone cysts and one osteosarcoma). Only one tumor (an aneurysmal bone cyst) showed positive staining for both FGF23 and SSTR2A. SSTR2A also commonly stained neoplastic and non-neoplastic endothelial cells. We conclude that neither FGF23 nor SSTR2A expression are specific for the diagnosis of PMT. However both stains are highly sensitive. Because of its diffuse strong expression and widespread availability, immunohistochemistry for SSTR2A is useful to confirm the diagnosis of PMT in an appropriate setting particularly if material is limited. Negative staining can serve as an excellent rule out test for this diagnosis.
Assuntos
Hipofosfatemia Familiar/diagnóstico , Mesenquimoma/diagnóstico , Neoplasias de Tecido Conjuntivo/diagnóstico , Osteomalacia/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Receptores de Somatostatina/metabolismo , Adulto , Medicamentos de Ervas Chinesas , Eleutherococcus , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Hipofosfatemia Familiar/metabolismo , Hipofosfatemia Familiar/patologia , Masculino , Mesenquimoma/metabolismo , Mesenquimoma/patologia , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/metabolismo , Neoplasias de Tecido Conjuntivo/patologia , Osteomalacia/metabolismo , Osteomalacia/patologia , Síndromes Paraneoplásicas/metabolismo , Síndromes Paraneoplásicas/patologiaRESUMO
Hypophosphatasia is an inheritable disorder characterized by defective bone mineralization and a deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity. Screening for mutations in the TNSALP gene allows genetic counseling and prenatal diagnosis of the disease in families with severe forms of hypophosphatasia. A 33-year-old, gravida 4, para 3 Japanese woman was referred to Nagoya City University Hospital for prenatal genetic counseling because of two previous occurrences of fetal bone anomalies. The molecular examination showed that the fetus was homozygous for the TNSALP gene mutation c.1559delT, each parent being heterozygous. Genetic counseling was offered and at the next pregnancy, chorionic villus sampling was performed, whereupon genetic analysis confirmed that the fetus did not carry the familial mutation c.1559delT. Postnatal molecular genetic analysis using the cord tissue can provide a diagnosis of lethal hypophosphatasia and prenatal genetic diagnosis of the TNSALP gene allows time for parental counseling and delivery planning.
Assuntos
Fosfatase Alcalina/genética , Hipofosfatemia Familiar/diagnóstico , Fosfatase Alcalina/sangue , Calcificação Fisiológica/genética , Amostra da Vilosidade Coriônica , Feminino , Testes Genéticos , Humanos , Hipofosfatemia Familiar/sangue , Hipofosfatemia Familiar/genética , Gravidez , Diagnóstico Pré-NatalRESUMO
The aim of this study was to analyse the clinical manifestations and the most frequent causes of osteomalacia (OM) in a group of 28 patients diagnosed with this disorder during a 20-year period. OM was diagnosed by bone biopsy and/or by Bingham and Fitzpatrick criteria (two of the following: low calcium, low phosphate, elevated total alkaline phosphatase [total AP] or suggestive radiographs). Of these patients, 13 had vitamin D deficiency OM (VD-OM), 14 hypophosphatemic OM (HypoP-OM) and one had OM-associated hypophosphatasia. Deficient sun exposure and celiac disease were the most frequent etiologies of VD-OM, whereas most HypoP-OM were hereditary forms. The main clinical symptoms were polyarthralgias (89%), frequently associated with fractures (75%). Fifty seven percent had densitometric criteria of osteoporosis. Patients with VD-OM showed significantly higher total AP and PTH serum values, but lower vitamin D, serum calcium, calciuria and bone mass than patients with HypoP-OM. Conversely, HypoP-OM patients had significantly lower serum phosphate and higher phosphaturia than patients with VD-OM. Briefly, high total AP, low serum calcium and low serum phosphate were observed in 85%, 65% and 15%, respectively, of patients with VD-OM, being observed in 64%, 14% and 100%, respectively, of HypoP-OM patients. Nearly 50% of these latter showed increased FGF23 levels. In conclusion, in this study, the frequencies of HypoP-OM and VD-OM were similar. The most frequent laboratory abnormalities were increased total AP and decreased serum phosphate. A urinary calcium loss of less than 50 mg/dl was highly discriminatory for VD-OM and a serum phosphate less than 2.3 mg/dl was also high discriminatory for HypoP-OM. Low densitometric values and fractures were frequent among these patients.
Assuntos
Osteomalacia/diagnóstico , Osteomalacia/terapia , Adulto , Idoso , Biópsia , Densidade Óssea , Osso e Ossos/patologia , Feminino , Fator de Crescimento de Fibroblastos 23 , Fraturas Ósseas , Humanos , Hipofosfatasia/complicações , Hipofosfatemia/complicações , Hipofosfatemia Familiar/diagnóstico , Masculino , Pessoa de Meia-Idade , Osteomalacia/complicações , Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/complicaçõesRESUMO
Hypercalcemia and hypophosphatemia are symptoms of two relatively rare hereditary diseases and are extraordinarily important from the standpoint of the differential diagnosis. Mutation in calcium sensing receptor gene (CaSR) clinically manifests as familial hypocalciuric hypercalcemia (FHH) or as the much more serious neonatal hyperparathyreosis. Hypercalciuric hypocalcemia is extremely rare. Prognosis for the most frequent mutations in the CaSR gene FHH is considered benign; nevertheless, if overlooked it can lead to an incorrect diagnosis of primary hyperparathyreosis, which has a fundamentally different prognosis and treatment. Familial hypophosphatemia sometimes occurs as hereditary rickets, which is a consequence of insufficient production of vitamin D-hormone or abnormal function of vitamin D receptors (VDR). The disease manifests as X-linked dominant hypophosphatemic rickets or autosomal dominant hypophosphatemic rickets. Autosomal recessive form is very rare. Oncogenic hypophosphatemia should be excluded in differential diagnosis. In this review the issues of pathogenesis, differential diagnosis and treatment of FHH and hypophosphatemic rickets are discussed.
Assuntos
Hipercalcemia/diagnóstico , Hipercalcemia/genética , Hipofosfatemia Familiar/diagnóstico , Fosfatos de Cálcio/metabolismo , Diagnóstico Diferencial , Humanos , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/genética , Mutação , Receptores de Detecção de Cálcio/genéticaRESUMO
Phosphaturic mesenchymal tumor is an extremely rare disease and is frequently associated with oncogenic osteomalacia showing paraneoplastic syndrome, which is characterized by phosphaturia, hypophosphatemia, normocalcemia, and decreased levels of 1,25-dihydroxyvitamin D3 associated with a tumor. A 2-year-old boy, who had a soft tissue tumor on his right thigh and previously diagnosed as myositis ossificans at 9-months-old, was presented with rachitic rosary and mildly enlarged tumor. Biochemical investigations showed hypophosphatemia, hyperphosphaturia, and an increased alkaline phosphatase level of 440 U/l (25-100 U/l), suggesting rickets, which was resistant to vitamin D dietary supplementation. We were certain of intractable rickets because of oncogenic hypophosphatemia and thus decided to excise the soft tissue mass. We observed laboratory improvement of rickets after 2 weeks. On the basis of surgical and histopathological examinations, the tumor was finally diagnosed as the phosphaturic mesenchymal tumor.
Assuntos
Raquitismo Hipofosfatêmico Familiar/diagnóstico , Hipofosfatemia Familiar/diagnóstico , Mesenquimoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Fosfatase Alcalina/sangue , Pré-Escolar , Diagnóstico Diferencial , Humanos , Hipofosfatemia Familiar/metabolismo , Lactente , Masculino , Mesenquimoma/metabolismo , Mesenquimoma/cirurgia , Miosite Ossificante/diagnóstico , Radiografia Torácica , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/cirurgia , Coxa da Perna/diagnóstico por imagem , Resultado do TratamentoRESUMO
An appropriate phosphate homeostasis is absolutely required for correct bone mineralization and remodeling, for diverse signaling pathways as well as cell membrane formation. Its disequilibrium results in serious complications like hypophosphatemia and excessively reduced fractional tubule phosphate reabsorption (TRP). A rare cause of such a disturbed phosphate balance is tumor-induced osteomalacia (TIO)--a phosphate wasting disorder sometimes associated with certain mesenchymal tumors. These primitive tumors secrete so-called phosphatonins--recently identified factors involved in the regulation of phosphate homeostasis such as the secreted frizzled related protein 4 (sFRP-4), the fibroblast growth factors 7 and 23 (FGF-7/-23), or the matrix extracellular phosphoglycoprotein (MEPE). Progressive muscular weakness and spontaneous bone fractures caused by inadequate osteoid mineralization are the characteristic clinical symptoms, which completely resolve after tumor resection. Here we report a new case of TIO caused by tumor secreted FGF-23 and review the literature to facilitate the correct diagnosis of this rare disorder.
Assuntos
Hipofosfatemia Familiar/complicações , Osteomalacia/etiologia , Síndromes Paraneoplásicas/etiologia , Fosfatos/urina , Adulto , Biópsia , Diagnóstico Diferencial , Fator de Crescimento de Fibroblastos 23 , Seguimentos , Humanos , Hipofosfatemia Familiar/diagnóstico , Hipofosfatemia Familiar/urina , Imageamento por Ressonância Magnética , Masculino , Osteomalacia/diagnóstico , Osteomalacia/urina , Síndromes Paraneoplásicas/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
A one year eight month old male child and his nine month old female sibling were presented with Growth retardation, abdominal distension, doll-like faces, hepatomegaly, phosphaturia, proximal renal tubular dysfunction. The elder sibling also presented with glucosuria, hyperglycemia, hypoinsulinemia. The younger one later presented with galactosemia. Biopsy of liver on these two patients revealed the accumulation of glycogen in hepatocytes.
Assuntos
Transtornos do Crescimento/diagnóstico , Hepatomegalia/diagnóstico , Hipofosfatemia Familiar/diagnóstico , Biópsia , Feminino , Glicogênio/metabolismo , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatomegalia/metabolismo , Hepatomegalia/patologia , Humanos , Hipofosfatemia Familiar/metabolismo , Hipofosfatemia Familiar/patologia , Lactente , Fígado/metabolismo , Fígado/patologia , Masculino , SíndromeAssuntos
Neoplasias Femorais/complicações , Neoplasias Femorais/diagnóstico , Hipofosfatemia Familiar/complicações , Hipofosfatemia Familiar/diagnóstico , Mesenquimoma/complicações , Mesenquimoma/diagnóstico , Osteomalacia/diagnóstico , Osteomalacia/etiologia , Idoso , Feminino , Humanos , Tomografia por Emissão de Pósitrons , Técnica de Subtração , Tomografia Computadorizada por Raios XRESUMO
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubulopathy resulting from mutation in the gene encoding paracelin 1. The main symptoms of FHHNC include excessive urinary calcium and magnesium excretion, nephrocalcinosis, and chronic renal failure. We present 16-year old girl in whom symptoms of FHHNC were accidentally recognized during therapy of acute lymphoblastic leukemia. In our patient, some symptoms of FHHNC were initially taken for the adverse effects of cytostatic therapy that delayed an adequate diagnosis. To the best of our knowledge, this is the first report of FHHNC associated with acute lymphoblastic leukemia. However, in our opinion this association is accidental.
Assuntos
Hipofosfatemia Familiar/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Feminino , Humanos , Hipercalciúria/complicações , Hipofosfatemia Familiar/complicações , Nefrocalcinose/complicaçõesRESUMO
In generalized arterial calcification of infancy (OMIM no. 208000), calcification of the media and proliferation of the intima lead to arterial stenoses. Most affected patients present with untreatable arterial hypertension and die within the first months of life. The disease has recently been linked to mutations in ENPP1. We report two siblings with prolonged survival, both of whom carry the compound heterozygous ENPP1 mutations c.913C>A and c.1164+2T>A. In both siblings, spontaneous regression of arterial calcifications occurred, and antihypertensive treatment could be tapered off gradually. In some patients, the natural course of GACI may be more favourable than previously assumed.
Assuntos
Doenças da Aorta/genética , Arteriopatias Oclusivas/genética , Calcinose/genética , Aberrações Cromossômicas , Genes Recessivos , Insuficiência Cardíaca/genética , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Sobreviventes , Aorta Abdominal , Doenças da Aorta/diagnóstico , Arteriopatias Oclusivas/diagnóstico , Calcinose/diagnóstico , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Criança , Pré-Escolar , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Hipofosfatemia Familiar/diagnóstico , Hipofosfatemia Familiar/genética , Recém-Nascido , Mutação de Sentido Incorreto , Gravidez , Diagnóstico Pré-Natal , Remissão Espontânea , Análise de Sequência de DNA , Ultrassonografia DopplerRESUMO
Hereditary hypophosphatemic rickets groups together X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR) and hereditary hypophosphatemic rickets with hypercalciuria (HHRH, autosomal recessive). Clinical and biological characteristics and treatment depend on specific etiology. Mutations causing hereditary hypophosphatemic rickets involve PHEX located on Xp11.22 for XLH and FGF-23 located on 12p13 for ADHR. The gene involved in HHRH remains unknown: candidates may encode proteins that modulate phosphate transporter expression or activity. Others forms of rickets must be ruled out: acquired hypophosphatemia due to oncogenic osteomalacia, X-linked recessive hypophosphatemic rickets or Dent's disease, and hereditary 1, 25-dihydroxyvitamin D-resistant rickets with a defect either in the 1-alpha-hydroxylase gene (pseudo-vitamin D deficiency rickets, PDDR) or in the vitamin D receptor (hereditary vitamin D-resistant rickets, HVDRR).