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2.
Drug Des Devel Ther ; 13: 1127-1133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118563

RESUMO

Adefovir dipivoxil (ADV) is one of the most important nucleostide analogues currently in use for the treatment of chronic hepatitis B virus (HBV) infection. Low-dose ADV-induced nephrotoxicity in most cases was reported to be reversible after the discontinuation of ADV or by decreasing the dose of ADV. In our study, we have 5 documented cases of low-dose ADV-induced hypophosphatemia osteomalacia with or without Fanconi syndrome which were diagnosed in our hospital between 2010 and 2017. Three patients were observed to have a full recovery after the discontinuation of ADV. Two patients had persistently elevated urine ß2-microglobulin levels and out of these two patients, one patient had persistent hypophosphatemia after the cessation of ADV. These cases illustrated that the use of low-dose ADV increased the risk of nephrotoxicity, and in some patients, low-dose ADV-induced nephrotoxicity was not completely reversible. Patients of East Asian origin, especially those with a low body mass index, were prone to a relatively higher risk of developing low-dose ADV-induced nephrotoxicity; therefore, it was worth paying attention to the side effects caused by low-dose ADV.


Assuntos
Adenina/análogos & derivados , Hepatite B Crônica/complicações , Hipofosfatemia/induzido quimicamente , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos , Osteomalacia/induzido quimicamente , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Idoso , Relação Dose-Resposta a Droga , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/complicações , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Hipofosfatemia/complicações , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Osteomalacia/complicações
3.
J. bras. nefrol ; 41(1): 131-141, Jan.-Mar. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1002426

RESUMO

Abstract Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.


Resumo A assistência a pacientes com doenças crônicas e raras é complexa, principalmente pela falta de disseminação de conhecimento sobre a doença, o que dificulta o diagnóstico preciso e precoce, além da necessidade da realização de exames específicos, por vezes de alta complexidade e custo. Somam-se a esses fatores dificuldades na obtenção de tratamento adequado quando disponível, na conscientização do paciente e da família sobre a doença e na aderência ao tratamento. A cistinose nefropática está entre essas doenças. Após mais de 20 anos como centro de atendimento a esses pacientes, os autores propõem um protocolo de seguimento, o qual vem sendo empregado com melhora na qualidade da assistência e consiste de uma abordagem multidisciplinar, incluindo, principalmente, atendimento prestado por médico, enfermeiro, psicólogo, nutricionista e assistente social. Neste artigo, cada área expõe de maneira objetiva como abordar pontos que envolvem as etapas do diagnóstico e sua comunicação ao paciente e a seus familiares ou responsáveis, abrangendo as particularidades da doença e do tratamento, o impacto na vida do paciente e de sua família, a abordagem das questões psicológicas e sociais e orientações quanto a medicamentos e dietas. Considera-se que este protocolo poderia ser adaptado ao seguimento de pacientes portadores de outras doenças raras, incluindo aquelas com envolvimento renal. Com essa proposta, espera-se alcançar o maior número de profissionais envolvidos no seguimento desses pacientes, fortalecendo as bases para a criação de um protocolo nacional, observando-se as particularidades de cada caso.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Cistinose/diagnóstico , Cistinose/terapia , Doenças Raras/diagnóstico , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamento farmacológico , Equipe de Assistência ao Paciente , Gravidez , Protocolos Clínicos , Diálise Renal , Transplante de Rim , Resultado do Tratamento , Cistinose/complicações , Cistinose/psicologia , Doenças Raras/complicações , Doenças Raras/psicologia , Doenças Raras/tratamento farmacológico , Diálise , Síndrome de Fanconi/complicações , Síndrome de Fanconi/psicologia , Falência Renal Crônica/etiologia
4.
J Bras Nefrol ; 41(1): 131-141, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30465592

RESUMO

Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.


Assuntos
Cistinose/diagnóstico , Cistinose/tratamento farmacológico , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamento farmacológico , Doenças Raras/diagnóstico , Doenças Raras/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Protocolos Clínicos , Cistinose/complicações , Cistinose/psicologia , Diálise , Síndrome de Fanconi/complicações , Síndrome de Fanconi/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Falência Renal Crônica/etiologia , Transplante de Rim , Masculino , Equipe de Assistência ao Paciente , Gravidez , Doenças Raras/complicações , Doenças Raras/psicologia , Diálise Renal , Resultado do Tratamento , Adulto Jovem
5.
Intern Med ; 58(6): 821-825, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30333420

RESUMO

A 68-year-old man with type 2 diabetes mellitus and chronic hepatitis B infection was referred to the nephrology department before planned surgery for hepatocellular carcinoma. He had been receiving low-dose adefovir dipivoxil (ADV) for 11 years. Laboratory findings revealed impaired re-absorption in the proximal renal tubules. He had been diagnosed with diabetic kidney disease and osteomalacia due to vitamin D deficiency; thus, ADV was not discontinued until he was referred to us. In this case, concomitant diabetes mellitus and vitamin D deficiency might have prevented the early diagnosis of ADV-induced Fanconi syndrome.


Assuntos
Adenina/análogos & derivados , Antivirais/efeitos adversos , Nefropatias Diabéticas/diagnóstico , Síndrome de Fanconi/diagnóstico , Hipofosfatemia/diagnóstico , Organofosfonatos/efeitos adversos , Osteomalacia/diagnóstico , Deficiência de Vitamina D/diagnóstico , Adenina/efeitos adversos , Adenina/uso terapêutico , Idoso , Antivirais/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Erros de Diagnóstico , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/complicações , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Hipofosfatemia/etiologia , Masculino , Organofosfonatos/uso terapêutico , Osteomalacia/etiologia
6.
Osteoporos Int ; 30(2): 519-523, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30171299

RESUMO

Denosumab, a novel agent that inhibits osteoclasts, reduces the risk of fracture in patients with osteoporosis. However, worsening of hypophosphatemia and other symptoms may be induced by denosumab in patients with pre-existing hypophosphatemic osteomalacia. A 58-year-old man with hepatitis B presented with diffuse bone pain and muscle weakness. Denosumab was prescribed by the orthopedist according to documented low bone mass and spine compression fracture. After administering denosumab, the patient's bone pain worsened, and he later developed a right tibia stress fracture. His condition was diagnosed as adult-onset hypophosphatemic osteomalacia complicated by multiple bone fractures, which resulted from Fanconi syndrome with proximal tubulopathy due to tenofovir disoproxil fumarate (TDF) treatment for his hepatitis B. Denosumab use leads to aggressive hypophosphatemic osteomalacia and the complication of stress fractures, because of its effects on bone resorption. Physicians should be aware that in patients with chronic hepatitis B monoinfection who are administered TDF therapy, bone pain or fracture is possible but preventable by timely monitoring of serum phosphate levels. Denosumab should not be used in patients with untreated osteomalacia or vitamin D deficiency, as it may lead not only to hypocalcemia but also to hypophosphatemia in these patients.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Denosumab/efeitos adversos , Síndrome de Fanconi/induzido quimicamente , Hipofosfatemia/induzido quimicamente , Osteomalacia/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Síndrome de Fanconi/complicações , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/etiologia , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Osteomalacia/diagnóstico por imagem , Radiografia , Cintilografia , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/etiologia , Tomografia Computadorizada por Raios X
7.
BMC Nephrol ; 19(1): 274, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340545

RESUMO

BACKGROUND: Tubulo-interstitial Nephritis and Uveitis (TINU) syndrome is a rare oculo-renal inflammatory disease. Renal tubular defects are usually found, but full proximal tubular abnormalities have rarely been described. CASE PRESENTATION: We report the case of a 55-year old woman, native from Morocco, presenting with bilateral, non-granulomatous, anterior uveitis, mild renal insufficiency, leucocyturia and glycosuria. Further work-up showed hypophosphatemia and hyperphosphaturia, hypouricemia and hyperuricosuria, and hyper aminoaciduria, consistent with Fanconi syndrome. A kidney biopsy was obtained and showed diffuse interstitial infiltrates with tubular necrosis. The patient improved after the initiation of a corticosteroid therapy, with tapering dose. CONCLUSIONS: We reviewed the literature and found nine similar cases. This association mostly occurs in adult woman, without current evidence for an ethnic predilection, unlike previously reported. The renal prognosis seems favorable after corticosteroid therapy, even in case of severe renal injury. Nonetheless mild tubular defects may persist after treatment or spontaneous remission.


Assuntos
Síndrome de Fanconi/complicações , Síndrome de Fanconi/diagnóstico , Nefrite Intersticial/complicações , Nefrite Intersticial/diagnóstico , Uveíte/complicações , Uveíte/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade
8.
BMC Nephrol ; 19(1): 144, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907094

RESUMO

BACKGROUND: Arthrogryposis-Renal dysfunction-Cholestasis syndrome (ARC, MIM#208085) is a rare multisystem disease due to mutations in the VPS33B and VIPAR genes, both involved in maintaining apical-basolateral cell polarity. The correlation between mutations and phenotype in the ARC Syndrome is not well described. We report on a 6 year old patient who presented with severe renal Fanconi as first manifestation of ARC related to a combined de novo mutation in the VPS33B gene. CASE PRESENTATION: A 6 year old girl presented during the first year of life with severe renal Fanconi as the first manifestation of ARC-Syndrome. This case presents all defining features of ARC syndrome (including liver, skin and articular manifestations) with predominantly renal impairment at presentation. This novel mutation may be associated with a pronounced renal phenotype in ARC. Furthermore, we report on the successful use of LDL-Apheresis and biliodigestive derivation for treatment of cholestatic pruritus with encouraging results. CONCLUSION: ARC is a heterogeneous disorder with early mortality. This case report contributes to a better understanding of this rare disorder, describes a novel mutation in the VPS33B gene and presents an innovative rescue treatment approach.


Assuntos
Artrogripose/diagnóstico , Artrogripose/terapia , Colestase/diagnóstico , Colestase/terapia , Gerenciamento Clínico , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/terapia , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Índice de Gravidade de Doença , Artrogripose/complicações , Remoção de Componentes Sanguíneos/métodos , Criança , Colestase/complicações , Síndrome de Fanconi/complicações , Feminino , Humanos , Insuficiência Renal/complicações
9.
BMJ Case Rep ; 20182018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735496

RESUMO

A 64-year-old woman had fragility fractures which caused her to have gross deformities and confined her to bed. These were initially ascribed to vitamin D deficiency. However, despite correction of the deficiency, she did not improve. A review of previous records already showed glucosuria in the absence of diabetes, but this finding was overlooked. Eight years into the disease, it was realised that the glucosuria despite normal blood sugar could also mean that the patient was losing other substances needed for proper bone formation. Further investigations showed hypophosphataemia, renal phosphate wasting, hypokalaemia, mild metabolic acidosis, alkaline urine pH, hypouricaemia and aminoaciduria, all compatible with a proximal renal tubular defect (Fanconi syndrome). The fragility fractures were due to poor bone mineralisation because of hypophosphataemia induced by the inability of the kidneys to conserve phosphorus.


Assuntos
Síndrome de Fanconi/complicações , Fraturas Ósseas/etiologia , Glicosúria/etiologia , Hipofosfatemia/etiologia , Túbulos Renais Proximais/anormalidades , Absorciometria de Fóton/métodos , Diagnóstico Diferencial , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/patologia , Síndrome de Fanconi/urina , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/cirurgia , Humanos , Hipopotassemia/etiologia , Hipopotassemia/metabolismo , Hipofosfatemia/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Pessoa de Meia-Idade , Fósforo/administração & dosagem , Fósforo/uso terapêutico , Resultado do Tratamento
10.
Am J Case Rep ; 19: 392-396, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29610453

RESUMO

BACKGROUND Sjögren's syndrome is a chronic inflammatory autoimmune disease, which is also known as sicca syndrome, due to the symptoms of dry eyes and dry mouth, and is associated with other connective tissue diseases and autoimmune diseases. Sjögren's syndrome can also be associated with renal involvement. Fanconi's syndrome is associated with impaired reabsorption in the proximal renal tubule associated with tubulointerstitial nephritis and is associated with renal tubular acidosis and hypophosphatemia. Osteomalacia is a rare association with Sjögren's syndrome, which may result from renal disease. CASE REPORT We report the case of a 34-year-old woman who presented with xerostomia, xerophthalmia, bone fractures, and osteomuscular pain. A Schirmer test showed reduced tear production, and a biopsy of a minor salivary gland of the lip, with high titers of antinuclear antibodies (ANA), and positive anti-SSA/Ro and anti-SSB/La antibodies confirmed the diagnosis of Sjögren's syndrome. Serum and urinary laboratories tests and clinical manifestations confirmed Fanconi's syndrome associated with osteomalacia. The patient was treated with potassium supplements, 25-hydroxyvitamin D (25(OH)D), hydroxychloroquine, mycophenolate mofetil, and prednisone, with a favorable response. CONCLUSIONS This case is of a rare association between Sjögren's syndrome, Fanconi's syndrome, and osteomalacia. Even though these are rare clinical associations, early detection can improve the quality of life and prevent further complications.


Assuntos
Síndrome de Fanconi/complicações , Osteomalacia/complicações , Síndrome de Sjogren/etiologia , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Antirreumáticos/uso terapêutico , Biópsia , Quimioterapia Combinada , Síndrome de Fanconi/diagnóstico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imagem por Ressonância Magnética , Ácido Micofenólico/uso terapêutico , Osteomalacia/diagnóstico , Potássio/uso terapêutico , Prednisona/uso terapêutico , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Tomografia Computadorizada por Raios X , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico
11.
J Am Soc Nephrol ; 29(7): 1849-1858, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29654216

RESUMO

Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure.Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations.Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death.Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.


Assuntos
Amidinotransferases/genética , Síndrome de Fanconi/genética , Falência Renal Crônica/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Idoso , Amidinotransferases/metabolismo , Animais , Simulação por Computador , Síndrome de Fanconi/complicações , Síndrome de Fanconi/metabolismo , Síndrome de Fanconi/patologia , Feminino , Heterozigoto , Humanos , Lactente , Inflamassomos/metabolismo , Falência Renal Crônica/etiologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Masculino , Camundongos , Camundongos Knockout , Conformação Molecular , Mutação , Mutação de Sentido Incorreto , Linhagem , Espécies Reativas de Oxigênio/metabolismo , Análise de Sequência de DNA , Adulto Jovem
12.
Nephrol Dial Transplant ; 33(9): 1525-1532, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29365190

RESUMO

Background: Bone impairment is a poorly described complication of nephropathic cystinosis (NC). The objectives of this study were to evaluate in vitro effects of cystinosin (CTNS) mutations on bone resorption and of cysteamine treatment on bone cells [namely human osteoclasts (OCs) and murine osteoblasts]. Methods: Human OCs were differentiated from peripheral blood mononuclear cells (PBMCs) of patients and healthy donors (HDs). Cells were treated with increasing doses of cysteamine in PBMCs or on mature OCs to evaluate its impact on differentiation and resorption, respectively. Similarly, cysteamine-treated osteoblasts derived from murine mesenchymal stem cells were assessed for differentiation and activity with toxicity and proliferation assays. Results: CTNS was expressed in human OCs derived from HDs; its expression was regulated during monocyte colony-stimulating factor- and receptor activator of nuclear factor-κB-dependent osteoclastogenesis and required for efficient bone resorption. Cysteamine had no impact on osteoclastogenesis but inhibited in vitro HD osteoclastic resorption; however, NC OC-mediated bone resorption was impaired only at high doses. Only low concentrations of cysteamine (50 µM) stimulated osteoblastic differentiation and maturation, while this effect was no longer observed at higher concentrations (200 µM). Conclusion: CTNS is required for proper osteoclastic activity. In vitro low doses of cysteamine have beneficial antiresorptive effects on healthy human-derived OCs and may partly correct the CTNS-induced osteoclastic dysfunction in patients with NC. Moreover, in vitro low doses of cysteamine also stimulate osteoblastic differentiation and mineralization, with an inhibitory effect at higher doses, likely explaining, at least partly, the bone toxicity observed in patients receiving high doses of cysteamine.


Assuntos
Reabsorção Óssea/metabolismo , Cistinose/fisiopatologia , Síndrome de Fanconi/complicações , Osteoclastos/patologia , Osteogênese/fisiologia , Animais , Reabsorção Óssea/etiologia , Diferenciação Celular , Células Cultivadas , Cistinose/complicações , Síndrome de Fanconi/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Camundongos , Osteoclastos/metabolismo
13.
Mod Rheumatol ; 28(5): 897-900, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27142563

RESUMO

We describe a 53-year-old woman with primary Sjögren's syndrome and tubulointerstitial nephritis showing distal renal tubular acidosis and Fanconi syndrome. The patient showed high serum IgM levels and positivity for antimitochondrial antibodies, although her liver function was in normal range. According to our literature review, 75% of patients with tubulointerstitial nephritis who were positive for antimitochondrial antibodies showed Fanconi syndrome, suggesting that these antibodies may directly be associated with the pathophysiology of Fanconi syndrome.


Assuntos
Acidose Tubular Renal/sangue , Autoanticorpos/sangue , Síndrome de Fanconi/sangue , Mitocôndrias/imunologia , Nefrite Intersticial/sangue , Síndrome de Sjogren/sangue , Acidose Tubular Renal/complicações , Acidose Tubular Renal/imunologia , Autoanticorpos/imunologia , Síndrome de Fanconi/complicações , Síndrome de Fanconi/imunologia , Feminino , Humanos , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Nefrite Intersticial/complicações , Nefrite Intersticial/imunologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/imunologia
14.
Pediatr Dev Pathol ; 21(1): 84-90, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28382841

RESUMO

Fanconi-Bickel syndrome is a rare autosomal recessive disorder due to mutations in the facilitative glucose transporter 2 ( GLUT2 or SLC2A2) gene resulting in excessive glycogen storage predominantly in the liver and kidney. Previous case reports of this condition have described liver biopsies with glycogen storage and variable steatosis and/or fibrosis. Unlike in other types of glycogen storage disease, hepatocellular adenomas and carcinomas have not been described to date in this syndrome. A 6-year-old boy with consanguineous parents had short stature, poorly controlled rickets, hepatosplenomegaly, and renal tubular dysfunction clinically consistent with Fanconi-Bickel Syndrome. Sequencing of the SLC2A2 gene showed a homozygous variant of unknown significance [c.474A > C (p.Arg158Ser)] causing a missense mutation in an evolutionarily conserved residue. An incidental single hepatic lesion was discovered on imaging, and subsequent resection showed a 2.6 cm well-differentiated hepatocellular carcinoma with moderate atypia, diffuse immunoreactivity for glypican-3, and nuclear b-catenin, and with focal complete loss of the reticulin framework. The non-neoplastic liver showed marked glycogen accumulation with mild periportal fibrosis, rare bridging fibrosis, and no regenerative or adenomatous nodules. By electron microscopy, tumor cells had pleomorphic nuclei, prominent nucleoli, and scant cytoplasm with numerous mitochondria. Well-developed canaliculi were occasionally seen. The non-neoplastic liver showed glycogenosis with abundant cytoplasmic free (non-membrane bound) glycogen. Hepatocellular carcinoma should be considered as a possible complication of Fanconi-Bickel syndrome. This well differentiated carcinoma did not appear to be associated with hepatic adenomatosis as has been described in some hepatocellular carcinomas associated with other hepatic glycogen storage disorders. The nuclear beta-catenin immunoreactivity indicates a role for the Wnt signaling pathway in the pathogenesis of this tumor.


Assuntos
Carcinoma Hepatocelular/etiologia , Síndrome de Fanconi/diagnóstico , Neoplasias Hepáticas/etiologia , Carcinoma Hepatocelular/diagnóstico , Criança , Síndrome de Fanconi/complicações , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino
15.
Pediatr Diabetes ; 19(1): 180-183, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28493372

RESUMO

Fanconi-Bickel syndrome is a rare inherited disease characterized by the combination of hepatorenal glycogen accumulation, proximal renal tubular dysfunction and impaired utilization of glucose and galactose. The first symptoms of the disorder are recognized in late infancy as clinical characteristics appear. Therapeutic approach is mainly conservative with supplements of calcium, phosphate and vitamin D and small frequent feedings to avoid hypoglycemia. We report 1 clinical case of very early diagnosis, a 19 days old baby girl, in which the first clinical sign of the disease was the detection of glycosuria and vomits. Serum alkaline phosphatase levels were very high without rickets. The patient presented postprandial hyperglycemia and fasting hypoglycemia. A complete 24-hour glucose profile was obtained using a continuous glucose monitoring system in real time, which was fundamental not only for the diagnosis but also for the prevention of hypoglycemia. She received frequent small meals, galactose-free milk diet, and oral intakes of calcium, phosphorum, bicarbonate and vitamin D supplements with good evolution and normal height and weight gain.


Assuntos
Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/complicações , Síndrome de Fanconi/metabolismo , Feminino , Glicosúria/etiologia , Humanos , Hiperglicemia/etiologia , Recém-Nascido
16.
Int J STD AIDS ; 29(3): 227-236, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28764611

RESUMO

The objective of this study was to determine the incidence and predictors of Fanconi Syndrome (FS) in a cohort of patients taking tenofovir disoproxil fumarate (TDF). Clinical records and laboratory investigations from patients receiving TDF between 2002 and 2016 were extracted. FS was defined as normoglycaemic glycosuria and proteinuria and at least one other marker of renal dysfunction. Regression analysis was performed with time to development of FS and the following covariates: ritonavir co-administration, age, gender, co-morbidities (hypertension, hyperlipidaemia, diabetes, viral hepatitis), CD4 cell count nadir and baseline eGFR. One thousand and forty-four patients received TDF without ritonavir and 398 patients with ritonavir. Thirteen cases of FS were identified with a mean duration of exposure of 55 months. The incidence of FS was 1.09/1000PY (0.54-1.63) of TDF exposure (without ritonavir) and 5.50/1000PY (3.66-7.33) of TDF-ritonavir co-administration (p=0.0057). The adjusted hazards ratio for ritonavir co-administration was 4.71 (1.37-16.14, p=0.014). Known risk factors for chronic kidney disease were not associated with development of FS. Ritonavir co-administration, but not other factors, is associated with a greater risk of FS. FS developed late. Known risk factors for chronic kidney disease and length of treatment are not useful for identifying patients most at risk of developing FS in patients taking TDF.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Síndrome de Fanconi/induzido quimicamente , Infecções por HIV/complicações , Nefropatias/induzido quimicamente , Proteinúria/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Fármacos Anti-HIV/uso terapêutico , Austrália/epidemiologia , Creatinina/urina , Síndrome de Fanconi/complicações , Síndrome de Fanconi/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Proteinúria/complicações , Insuficiência Renal Crônica/epidemiologia , Tenofovir/uso terapêutico
18.
Medicine (Baltimore) ; 96(46): e8760, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29145330

RESUMO

RATIONALE: We report a case of a hepatitis B virus (HBV)-positive patient with preexisting bone disease who developed tenofovir-induced Fanconi syndrome and subsequently sustained pathologic fracture. To our best knowledge, this is the first report in the English literature about pathologic femoral fracture due to tenofovir-induced Fanconi syndrome in patient with chronic hepatitis B (CHB). The present report describes detailed our experience with the diagnosis of pathologic femoral fracture due to tenofovir-induced Fanconi syndrome and treatment. PATIENT CONCERNS: A 45-year-old man visited our hospital with pain in the right thigh region and gait disturbance which had started 3 months ago and worsened 1 week before admission. The patient was diagnosed with CHB in 2004. He was on lamivudine medication for 2 years. Medication for the patient was subsequently changed to adefovir in 2009 and tenofovir disoproxil fumarate (TDF) in 2013. He was on TDF since 2013. DIAGNOSIS: His hip joint magnetic resonance imaging (MRI) revealed hypointensity lesions and cortical bone destruction in fat-saturated MR image at the iliopsoas muscle attachment site of the lesser trochanter of both femur. On blood test showed 25-OH vitamin D level at 6.42 ng/mL (normal range, >20 ng/mL) and U-deoxypyridinoline level at 7.60 nM/mMcr (normal range, 2.30-5.40 nM mMcr). However, osteocalcin and parathyroid hormone levels were within normal range. Based on these findings, the present case was concluded as tenoforvir-induced Fanconi syndrome. INTERVENTIONS: TDF treatment was discontinued. After cooperation with internal medicine department, in order to prevent further fractures of the right lesser trochanter, internal fixation was performed under spinal anesthesia using compression hip nails (APIS, TDM, Korea). OUTCOMES: Positive outcome by medication and operation demonstrates that his phosphorus and serum calcium levels were maintained within normal range and pain in the right thigh region was improved from visual analogue pain score (VAS) 7 before surgery to VAS 2 after surgery. LESSONS: Physicians need to regularly monitor bone metabolism in patients with take in tenofovir for early diagnosis before its progression to pathologic fractures.


Assuntos
Antivirais/efeitos adversos , Síndrome de Fanconi/complicações , Fraturas do Fêmur/etiologia , Fraturas Espontâneas/etiologia , Hepatite B Crônica/tratamento farmacológico , Tenofovir/efeitos adversos , Síndrome de Fanconi/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade
19.
BMC Nephrol ; 18(1): 275, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28851305

RESUMO

BACKGROUND: An increasing number of case reports suggest that acquired renal Fanconi syndrome may be associated with prolonged use of adefovir against hepatitis B virus. Renal Fanconi syndrome is an uncommon disease, and its complication with nephrolithiasis is quite rare. Herein, we report a rare coexistence of nephrolithiasis and acquired renal Fanconi syndrome in a chronic hepatitis B-positive patient with prolonged adefovir therapy. CASE PRESENTATION: The patient presented with osteomalacia and nephrolithiasis. Consequently, extracorporeal shock-wave lithotripsy and left double-J ureteral stent insertion were considered for obstructive nephropathy, which was caused by nephrolithiasis. However, osteomalacia had been misdiagnosed as osteoporosis before admission to our hospital. On admission, a complexity of multiple fractures, hypophosphataemia, glycosuria without hyperglycaemia and non-anion-gap metabolic acidosis indicated a diagnosis of acquired renal Fanconi syndrome induced by adefovir. After switching from adefovir to entecavir, the patient's symptoms and laboratory findings improved significantly. CONCLUSIONS: The mechanism responsible for nephrolithiasis in renal Fanconi syndrome is still unclear. We recommend regularly monitoring renal function and serum calcium and serum phosphate to prevent renal Fanconi syndrome during the prolonged use of adefovir for hepatitis B virus.


Assuntos
Adenina/análogos & derivados , Antivirais/efeitos adversos , Síndrome de Fanconi/diagnóstico por imagem , Hepatite B/diagnóstico por imagem , Nefrolitíase/diagnóstico por imagem , Organofosfonatos/efeitos adversos , Osteomalacia/diagnóstico por imagem , Adenina/efeitos adversos , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/complicações , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Nefrolitíase/complicações , Osteomalacia/complicações
20.
BMC Nephrol ; 18(1): 230, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28693455

RESUMO

BACKGROUND: Rare diseases may elude diagnosis due to unfamiliarity of the treating physicians with the specific disorder. Yet, advances in genetics have tremendously enhanced our ability to establish specific and sometimes surprising diagnoses. CASE PRESENTATION: We report a case of renal Fanconi syndrome associated with intermittent hypoglycemic episodes, the specific cause for which remained elusive for over 30 years, despite numerous investigations, including three kidney and one liver biopsy. The most recent kidney biopsy showed dysmorphic mitochondria, suggesting a mitochondrial disorder. When her son presented with hypoglycemia in the neonatal period, he underwent routine genetic testing for hyperinsulinemic hypoglycemia, which revealed a specific mutation in HNF4A. Subsequent testing of the mother confirmed the diagnosis also in her. CONCLUSION: Modern sequencing technologies that test multiple genes simultaneously enable specific diagnoses, even if the underlying disorder was not clinically suspected. The finding of mitochondrial dysmorphology provides a potential clue for the mechanism, by which the identified mutation causes renal Fanconi syndrome.


Assuntos
Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/genética , Fator 4 Nuclear de Hepatócito/genética , Procurador , Síncope/diagnóstico , Síncope/genética , Adulto , Síndrome de Fanconi/complicações , Feminino , Seguimentos , Testes Genéticos/tendências , Humanos , Recém-Nascido , Masculino , Síncope/complicações
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