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1.
Nihon Shokakibyo Gakkai Zasshi ; 116(4): 353-359, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30971673

RESUMO

A woman in her 60s visited our hospital due to elevation of ALP (1357U/L). The patient had been treated with lamivudine (LAM) in 2005, LAM+adefovir (ADV) in 2009, and ADV+entecavir in 2015 for chronic hepatitis B (CH-B). The ALP isozyme was predominantly bone type. Urinary ß-2 microglobulin (MG) and α-1MG increased to 49635µg/L and 64.1mg/L, respectively. Though no fractures were found during bone scintigraphy, the patient was diagnosed with Fanconi syndrome. However, 3 months after switching from ADV to tenofovir alafenamide (TAF), ALP decreased to 856U/L, and urinary ß-2MG and α-1MG decreased to 624µg/L and 6.0mg/L, respectively. Fanconi syndrome should be considered when an increase in ALP is observed in patients treated with ADV, and urinary ß-2MG and α-1MG assays are useful for establishing a diagnosis. Switching from ADV to TAF was an effective therapeutic option.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Síndrome de Fanconi/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , DNA Viral , Farmacorresistência Viral , Quimioterapia Combinada , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/metabolismo , Feminino , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
J Med Case Rep ; 13(1): 99, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31003599

RESUMO

BACKGROUND: Adefovir dipivoxil is a nucleotide analogue that is approved for treatment of chronic hepatitis B. Adefovir dipivoxil is associated with proximal tubular dysfunction, resulting in Fanconi syndrome, which can cause secondary hypophosphatemic osteomalacia. We describe a case of a patient with hypophosphatemic osteomalacia secondary to Fanconi syndrome induced by adefovir dipivoxil concomitantly with osteoporosis in whom clinical symptoms were improved by adding denosumab (a human monoclonal antibody targeting the receptor activator of nuclear factor-κB ligand) to preceding administration of vitamin D3. CASE PRESENTATION: A 60-year-old Japanese man had been receiving low-dose adefovir dipivoxil (10 mg/day) to treat chronic hepatitis B for approximately 5 years. He presented to an orthopedic surgeon with severe pain of the right hip and no trauma history, and fracture of the neck of the right femur was identified. In addition, 99mTc-hydroxymethylene diphosphate scintigraphy revealed significantly abnormal uptake in the bilateral ribs, hips, and knees, and he was therefore referred to our university hospital for evaluation of multiple pathological fractures. We diagnosed hypophosphatemic osteomalacia due to Fanconi syndrome induced by adefovir dipivoxil therapy. Although we reduced the patient's adefovir dipivoxil dose and added calcitriol (active vitamin D3), he did not respond and continued to complain of bone pain. Several bone resorption markers and bone-specific alkaline phosphatase were also persistently elevated. Therefore, we added denosumab to vitamin D3 supplementation for treatment of excessive bone resorption. Two months after initiation of denosumab, his hip and knee pain was relieved, along with a decrease in serum alkaline phosphatase and some bone resorption markers. CONCLUSIONS: Although denosumab is not generally an appropriate treatment for acquired Fanconi syndrome, it may be useful for patients who have hypophosphatemic osteomalacia due to adefovir dipivoxil-induced Fanconi syndrome associated with excessive bone resorption. However, clinicians should keep in mind that if denosumab is administered to patients with hypophosphatemic osteomalacia accompanied by excessive bone resorption, adequate vitamin D and/or phosphate supplementation should be done before administration of denosumab.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Denosumab/administração & dosagem , Síndrome de Fanconi/induzido quimicamente , Hipofosfatemia , Osteomalacia , Adenina/efeitos adversos , Adenina/análogos & derivados , Adulto , Antivirais/efeitos adversos , Síndrome de Fanconi/tratamento farmacológico , Hepatite B/tratamento farmacológico , Humanos , Hipofosfatemia/induzido quimicamente , Hipofosfatemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Osteomalacia/induzido quimicamente , Osteomalacia/tratamento farmacológico , Tomografia Computadorizada de Emissão , Resultado do Tratamento
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.
Ann Hematol ; 98(5): 1095-1100, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30511139

RESUMO

Light chain-associated Fanconi syndrome (LCFS) is a disorder of renal proximal tubule due to immunoglobulin light chains. Cases of LCFS are rare and mostly sporadically reported, and treatment of this entity is still controversial. This single-center retrospective study included 22 patients diagnosed with LCFS in Peking Union Medical College Hospital. Monoclonal gammopathy of undetermined significance was diagnosed in 13 patients, and overt multiple myeloma in six patients, with two smoldering myeloma and one Waldenstrom macroglobulinemia. Light chain was mostly kappa type (90.9%). Baseline median estimated glomerular filtration rate was 66 (13-126) ml/min/1.73 m2, with one patient presented as end-stage renal disease. After a median follow-up of 37 months, three patients died. Twelve patients were treated with chemotherapy, including 7 with bortezomib-based regimens. Renal function was significantly improved in the group of patients who received chemotherapy (p = 0.026). Compared with other chemotherapy regimens, patients with bortezomib-based treatment had a better hematological response (p = 0.027) as well as a better proximal tubule outcome (p = 0.015). Chemotherapy likely outweighs supportive treatment in patients with LCFS. Bortezomib-based regimen seems to be a safe first-line therapy for management of those patients.


Assuntos
Bortezomib/administração & dosagem , Síndrome de Fanconi , Taxa de Filtração Glomerular , Túbulos Renais/fisiopatologia , Adulto , Idoso , Bortezomib/efeitos adversos , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/fisiopatologia , Feminino , Seguimentos , Humanos , Cadeias Leves de Imunoglobulina , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/fisiopatologia , Estudos Retrospectivos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/fisiopatologia
6.
Medicine (Baltimore) ; 97(36): e12027, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30200082

RESUMO

RATIONALE: Renal Fanconi syndrome (FS) is a rare complication of monoclonal gammopathy. It is characterized by the impairment of renal proximal tubular function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia, hypouricemia and proximal renal tubular acidosis. Renal impairment in monoclonal gammopathy, without fulfilling the criteria of multiple myeloma, is categorized as monoclonal gammopathy of renal significance (MGRS). PATIENT CONCERNS: A 54-year-old male presented with progressively aggravated bone pain and limitation of activity was admitted to our department. A proximal renal tubular damage was suggested by hypophosphatemia, compensated metabolic acidosis, renal glycosuria, aminoaciduria, and hypouricemia. M-protein of IgA kappa was detected by immunofixation electrophoresis. Mildly increased plasma cells were found in bone marrow cytomorphologic examination. Renal biopsy revealed diffuse linear monoclonal IgA-kappa light chain deposits along tubular basement membranes (TBMs), while lambda was negative. Electron microscopy showed granular electron-dense deposits along the outer aspect of TBMs. DIAGNOSES: The patient was diagnosed as FS induced osteomalacia secondary to monoclonal gammopathy of renal significance (MGRS) (IgA-κ type) and LCDD. INTERVENTIONS: He was treated with bortezomib, supplementation by phosphate, alkali agents, and active vitamin D. He responded well to the treatment symptomatically. OUTCOMES: We reported a rare case of adult acquired FS with hypophosphatemic osteomalacia secondary to LCDD associated with MGRS and the patient was successfully treated with bortezomib. LESSONS: Although few cases of LCDD with isolated symptoms of tubulointerstitial nephropathy, rather than glomerular symptoms have been reported. It still needs to be recognized as a differential diagnosis in monoclonal gammopathy.


Assuntos
Síndrome de Fanconi/etiologia , Cadeias kappa de Imunoglobulina/análise , Nefropatias/complicações , Paraproteinemias/complicações , Diagnóstico Diferencial , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/patologia , Humanos , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Paraproteinemias/diagnóstico , Paraproteinemias/tratamento farmacológico , Paraproteinemias/patologia
7.
Adv Chronic Kidney Dis ; 25(4): 351-357, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30139461

RESUMO

Proximal renal tubular acidosis (pRTA) is an inherited or acquired clinical syndrome in which there is a decreased bicarbonate reclamation in the proximal tubule resulting in normal anion gap hyperchloremic metabolic acidosis. In children, pRTA may be isolated but is often associated with a general proximal tubular dysfunction known as Fanconi syndrome which frequently heralds an underlying systemic disorder from which it arises. When accompanied by Fanconi syndrome, pRTA is characterized by additional renal wasting of phosphate, glucose, uric acid, and amino acids. The most common cause of inherited Fanconi syndrome in the pediatric age group is cystinosis, a disease with therapeutic implications. In this article, we summarize the clinical presentation and differential diagnosis of pRTA and Fanconi syndrome and provide a practical approach to their evaluation in children.


Assuntos
Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/etiologia , Síndrome de Fanconi/etiologia , Acidose Tubular Renal/tratamento farmacológico , Acidose Tubular Renal/genética , Criança , Cistinose/complicações , Doença de Dent/complicações , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/genética , Humanos , Túbulos Renais Proximais , Síndrome Oculocerebrorrenal/complicações
8.
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
9.
Internist (Berl) ; 59(8): 861-867, 2018 08.
Artigo em Alemão | MEDLINE | ID: mdl-29671012

RESUMO

This article presents a case of cystinosis in a young man. Diagnosis of the disease and the problem of transition to adult care are described. Cystinosis is a rare lysosomal storage disease with first manifestation in early childhood presenting as renal Fanconi syndrome. Without treatment, the disease leads to severe health impairment. Due to the rarity of the disease, a correct diagnosis is often delayed. Without treatment, cystinosis often leads to end-stage renal failure, blindness, hypothyroidism, diabetes mellitus, and rickets. Cystine-depleting therapy with cysteamine significantly improves mortality and quality of life.


Assuntos
Cisteamina/uso terapêutico , Eliminadores de Cistina/uso terapêutico , Cistina/sangue , Cistina/metabolismo , Cistinose/diagnóstico , Cistinose/tratamento farmacológico , Síndrome de Fanconi/tratamento farmacológico , Adulto , Criança , Pré-Escolar , Cisteamina/administração & dosagem , Eliminadores de Cistina/administração & dosagem , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/etiologia , Humanos , Rim/patologia , Lisossomos/metabolismo , Masculino , Qualidade de Vida
10.
J Int Med Res ; 46(8): 3487-3490, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29614898

RESUMO

We herein report two cases of Fanconi syndrome with refractory hypophosphatemic osteomalacia that was difficult to correct by phosphorus replacement therapy. The pathological result was a bony giant cell tumor and osteosarcoma, respectively. Interestingly, after resection of the tumors, the patient with osteosarcoma recovered completely but the patient with the bony giant cell tumor had a relapse. Although she underwent nine operations, her symptoms and laboratory tests did not improve. These findings indicate that Fanconi syndrome can result from a bone tumor.


Assuntos
Neoplasias Ósseas/complicações , Síndrome de Fanconi/etiologia , Tumor de Células Gigantes do Osso/complicações , Osteossarcoma/complicações , Adulto , Criança , Síndrome de Fanconi/tratamento farmacológico , Feminino , Humanos , Hipofosfatemia/tratamento farmacológico , Hipofosfatemia/etiologia , Osteomalacia/tratamento farmacológico , Osteomalacia/etiologia , Compostos de Fósforo/administração & dosagem
11.
BMC Nephrol ; 18(1): 300, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28950840

RESUMO

BACKGROUND: Cystinosis is a rare autosomal recessive lysosomal disorder characterized by the accumulation of cystine in lysosomes. Cystinosis is much rarer in Asian than Caucasian populations. There are only 14 patients have with cystinosis alive in Japan. Most cystinosis is the nephropathic infantile form, as indicated by its apparent and severe clinical manifestations, including renal and ocular symptoms. Patients with the nephropathic juvenile form account for 5% of those with cystinosis. Their diagnosis is frequently delayed and difficult because of slower progression to end-stage renal disease and fewer cystine crystals in the cornea. Molecular analysis and a cysteine-binding protein assay should be performed when patients with proximal tubulopathy of an unknown origin are encountered. CASE PRESENTATION: A 12-year-old boy had been suffering from Fanconi syndrome since he was 3 years old. He was only recently diagnosed despite repeated ophthalmological examinations. Corneal cystine crystals were found when he was 12 years old, and he was diagnosed with cystinosis by high free cystine content in granulocytes (6.36 nmol half-cystine/mg protein, normal: <0.15). Analysis of the CTNS gene showed two novel heterozygous single nucleotide substitutions of c.329G > C and c.329 + 2 T > C. Both were splicing site variants causing exon 6 skipping proven by transcript analysis, although the functional prediction site showed c.329G > C, p.(Gly110Ala) as a benign missense substitution. The patient's estimated glomerular filtration rate was 66.8 mL/min/1.73 m2. He was immediately treated with cysteamine after diagnosis. CONCLUSIONS: Even if no ophthalmological abnormalities are present, nephropathic juvenile cystinosis should be suspected in children with Fanconi syndrome. Transcript analysis was useful to detect pathogenic splicing variants in this patient.


Assuntos
Cistinose/diagnóstico , Cistinose/genética , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Criança , Cisteamina/uso terapêutico , Cistinose/tratamento farmacológico , Síndrome de Fanconi/tratamento farmacológico , Humanos , Masculino , Síndrome Nefrótica/tratamento farmacológico , Microscopia com Lâmpada de Fenda/métodos
12.
Curr Med Res Opin ; 33(11): 2065-2076, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28692321

RESUMO

OBJECTIVES: To summarize available clinical evidence for cysteamine bitartrate preparations in the treatment of nephropathic cystinosis as identified through a systematic literature review (SLR). METHODS: We searched MEDLINE, MEDLINE In-Process and Embase using Ovid with a predefined search strategy through 19 January 2016. All publicly available clinical reports on the use of delayed-release (DR) cysteamine bitartrate (Procysbi 1 ) or immediate-release (IR) cysteamine bitartrate (Cystagon 2 ) in patients with cystinosis were included. RESULTS: We identified a total of 103 publications and 10 trial records. Of these, 9 studies describe DR cysteamine bitartrate (n = 267 patients), 42 describe IR cysteamine bitartrate (n = 1,427 patients) and in 53 studies the exact preparation was not specified (n = 906 patients). The vast majority of the studies used a non-randomized study design, with randomized clinical trials (RCTs) being scarce (1 study comparing DR and IR formulation) and case reports (n = 49) being the most common study design representing 47% of the total. CONCLUSION: A substantial evidence base for cysteamine bitartrate in the treatment of nephropathic cystinosis was identified. However, the majority of the evidence was of relatively low quality, with evidence levels of 3 or 4.


Assuntos
Cisteamina/uso terapêutico , Cistinose/tratamento farmacológico , Síndrome de Fanconi/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Mod Rheumatol ; 27(3): 545-547, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-25698227

RESUMO

A 77-year-old female with renal dysfunction, hypercalcemia, and hypercalciuria was presented. Systemic investigations including renal biopsy showed that the patient had Fanconi syndrome secondary to renal sarcoidosis. Treatment with 25 mg per day of prednisolone was initiated and her condition improved. Complication of Fanconi syndrome in patients with sarcoidosis is extremely rare. Although the pathological mechanism is still unknown, corticosteroid therapy was effective for ameliorating proteinuria, glycosuria, hypercalciuria, and aminoaciduria.


Assuntos
Anti-Inflamatórios/uso terapêutico , Síndrome de Fanconi/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Sarcoidose/complicações , Idoso , Anti-Inflamatórios/administração & dosagem , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/etiologia , Feminino , Glucocorticoides/administração & dosagem , Humanos , Prednisolona/administração & dosagem , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico
14.
Horm Res Paediatr ; 86(5): 337-341, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27245055

RESUMO

BACKGROUND: The p.R63W mutation in the hepatocyte nuclear factor-4 alpha (HNF4A) results in macrosomia and atypical Fanconi syndrome, in addition to hyperinsulinaemic hypoglycaemia (HI). We describe 2 infants carrying this mutation, presenting with additional features. Cases Series: Patient 1, a male born with a birth weight of 1.7 SDS, was diagnosed with HI on day 2 of life. He responded to 3-10 mg/kg/day of diazoxide. Raised serum creatinine led to the investigation of renal tubular function, showing leaking of electrolytes and protein. The patient also had conjugated hyperbilirubinaemia with liver steatosis. Patient 2 was a male born with a weight of 0.36 SDS. His mother had renal Fanconi syndrome. He received parenteral nutrition and presented with HI at 1 month of age, while establishing enteral feeds. Biochemistry workup showed renal tubular leaking of calcium, sodium, and phosphate. A hypoglycaemia screen documented HI, and the patient was commenced on 2 mg/kg/day of diazoxide. Continuous glucose monitoring was performed in his mother, revealing overnight hypoglycaemia. CONCLUSION: Renal Fanconi syndrome represents the only HNF4A feature showing complete penetrance. Our cases suggest that the p.R63W HNF4A mutation must be considered in subjects with a normal birth weight and postulate the possibility of liver involvement as a part of this condition.


Assuntos
Hiperinsulinismo Congênito/genética , Síndrome de Fanconi/genética , Fator 4 Nuclear de Hepatócito/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Glicemia/metabolismo , Hiperinsulinismo Congênito/sangue , Hiperinsulinismo Congênito/tratamento farmacológico , Diazóxido/administração & dosagem , Síndrome de Fanconi/sangue , Síndrome de Fanconi/tratamento farmacológico , Humanos , Recém-Nascido , Masculino
15.
Kidney Int ; 89(6): 1192-203, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27181776

RESUMO

Nephropathic cystinosis is an autosomal recessive metabolic, lifelong disease characterized by lysosomal cystine accumulation throughout the body that commonly presents in infancy with a renal Fanconi syndrome and, if untreated, leads to end-stage kidney disease (ESKD) in the later childhood years. The molecular basis is due to mutations in CTNS, the gene encoding for the lysosomal cystine-proton cotransporter, cystinosin. During adolescence and adulthood, extrarenal manifestations of cystinosis develop and require multidisciplinary care. Despite substantial improvement in prognosis due to cystine-depleting therapy with cysteamine, no cure of the disease is currently available. Kidney Disease: Improving Global Outcomes (KDIGO) convened a Controversies Conference on cystinosis to review the state-of-the-art knowledge and to address areas of controversies in pathophysiology, diagnostics, monitoring, and treatment in different age groups. More importantly, promising areas of investigation that may lead to optimal outcomes for patients afflicted with this lifelong, systemic disease were discussed with a research agenda proposed for the future.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Cisteamina/uso terapêutico , Eliminadores de Cistina/uso terapêutico , Cistina/metabolismo , Cistinose/etiologia , Doenças Raras/etiologia , Adolescente , Adulto , Fatores Etários , Criança , Congressos como Assunto , Cisteamina/efeitos adversos , Eliminadores de Cistina/efeitos adversos , Cistinose/complicações , Cistinose/diagnóstico , Cistinose/terapia , Síndrome de Fanconi/complicações , Síndrome de Fanconi/tratamento farmacológico , Testes Genéticos , Terapia Genética , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressão/efeitos adversos , Lactente , Falência Renal Crônica/etiologia , Transplante de Rim/efeitos adversos , Lisossomos/metabolismo , Mutação , Doenças Raras/complicações , Doenças Raras/diagnóstico , Doenças Raras/terapia , Diálise Renal
17.
Hum Genomics ; 10: 2, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26742487

RESUMO

BACKGROUND: Proximal tubular dysfunction (PTD) is associated with a decreased long-term graft survival in renal transplant patients and can be detected by the elevation of urinary tubular proteins. This study investigated transcriptional changes in biopsies from renal transplant patients with PTD to disclose molecular mechanisms underlying graft injury and functional recovery. METHODS: Thirty-three renal transplant patients with high urinary levels of retinol-binding protein, a biomarker of PTD, were enrolled in the study. The initial immunosuppressive scheme included azathioprine, cyclosporine, and steroids. After randomization, 18 patients (group 2) had their treatment modified by reducing cyclosporine dosage and substituting azathioprine for mycophenolate mofetil, while the other 15 patients (group 1) remained under the initial scheme. Patients were biopsied at enrollment and after 12 months of follow-up, and paired comparisons were performed between their intragraft gene expression profiles. The differential transcriptome profiles were analyzed by constructing gene co-expression networks and identifying enriched functions and central nodes in each network. RESULTS: Only the alternative immunosuppressive scheme used in group 2 ameliorated renal function and tubular proteinuria after 12 months of follow-up. Intragraft molecular changes observed in group 2 were linked to autophagy, extracellular matrix, and adaptive immunity. Conversely, gene expression changes in group 1 were related to fibrosis, endocytosis, ubiquitination, and endoplasmic reticulum stress. CONCLUSION: These results suggest that molecular networks associated with the control of endocytosis, autophagy, protein overload, fibrosis, and adaptive immunity may be involved in improvement of graft function.


Assuntos
Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/genética , Imunossupressão/métodos , Transplante de Rim/efeitos adversos , Transcriptoma/genética , Adulto , Idoso , Azatioprina/administração & dosagem , Ciclosporina/administração & dosagem , Síndrome de Fanconi/imunologia , Síndrome de Fanconi/urina , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genômica , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Proteínas Celulares de Ligação ao Retinol/urina , Esteroides/administração & dosagem
18.
Med Mol Morphol ; 49(1): 48-52, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26141649

RESUMO

In a case of acquired Fanconi syndrome associated with smoldering myeloma, we confirmed the deposition of protease-resistant κ light chain proteins in a proximal tubular injury and found the decreased expression of apical tubular transporters including sodium glucose co-transporter, sodium phosphate co-transporter, uric acid transporter 1, and a decrease of Na(+)/K(+)-ATPase in the basolateral membrane. The protease-resistant kappa light chain has a pathological role in the expression of tubular transporters in the proximal tubule and causes Fanconi syndrome associated with smoldering myeloma.


Assuntos
Síndrome de Fanconi/metabolismo , Cadeias kappa de Imunoglobulina/metabolismo , Túbulos Renais Proximais/metabolismo , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/etiologia , Feminino , Humanos , Túbulos Renais Proximais/patologia , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Osteomalacia/metabolismo , Peptídeo Hidrolases/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
19.
J Feline Med Surg ; 18(12): 1034-1040, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26170278

RESUMO

CASE SERIES SUMMARY: Fanconi syndrome (FS) is well described in humans and dogs, but has not been reported in cats. This case series describes four cats with acquired FS. On the basis of clinical signs and intestinal biopsies, all cats were initially diagnosed with alimentary lymphoma or inflammatory bowel disease. Treatment with chlorambucil and corticosteroids was started at standard doses, based on published protocols. Within 2-26 months of the start of treatment, glucosuria, despite normoglycemia, was identified incidentally on routine biochemical screening; FS was diagnosed with urine metabolic assays, confirming aminoaciduria and glucosuria in all four cases. Neither polyuria nor polydipsia were noted in any case, and only 1/4 cats had any clinical signs at the time of diagnosis. Partial or complete resolution of FS was seen in 3/4 cases within 3 months of discontinuing chlorambucil therapy. RELEVANCE AND NOVEL INFORMATION: This is the first case series to document acquired FS in the cat, and the first to suggest a possible association between chlorambucil and acquired FS. Cats treated with chlorambucil should be monitored for the development of glucosuria, and discontinuation of chlorambucil should be considered if FS is identified. Further study into the association between chlorambucil and acquired FS in cats is warranted.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Doenças do Gato/diagnóstico , Clorambucila/uso terapêutico , Síndrome de Fanconi/veterinária , Animais , Antineoplásicos Alquilantes/administração & dosagem , Doenças do Gato/tratamento farmacológico , Gatos , Clorambucila/administração & dosagem , Diagnóstico Diferencial , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamento farmacológico , Feminino , Masculino
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