Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
Zhonghua Gan Zang Bing Za Zhi ; 29(2): 172-174, 2021 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-33685088

RESUMO

Caroli's disease is a rare congenital disease characterized by non-obstructive dilatation of the intrahepatic bile ducts, with a prevalence of one in a million in the general population[1]. Most of it is considered to be an autosomal recessive genetic disease, but in many cases, the typical genetic family history cannot be traced back. There are two forms of Caroli's disease: simple type (commonly called Caroli disease) and Caroli syndrome (characterized by congenital liver fibrosis and/or polycystic kidney disease). PKHD1 gene is considered to be the causative gene of Caroli's disease, congenital liver fibrosis and/or polycystic kidney disease [2]. Here, we introduce a case of Caroli's disease confirmed by pathology, atypical symptoms and images in our hospital.


Assuntos
Doença de Caroli , Doenças Renais Policísticas , Ductos Biliares Intra-Hepáticos/patologia , Doença de Caroli/genética , Humanos , Cirrose Hepática/patologia , Doenças Renais Policísticas/patologia
3.
Clin J Gastroenterol ; 12(2): 106-111, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30343465

RESUMO

Herein we present a clinical case of the Caroli syndrome caused by the compound heterozygous mutation in the PKHD1 gene. Histopathological assessment of liver detected biliary cirrhosis, numerous dilated bile ducts of various sizes, hyperplastic cholangiocytes containing a large amount of acid mucopolysaccharides, decreased ß-tubulin expression and increased proliferation of cholangiocytes. A significant proportion of hepatic tissue was composed of giant cysts lined with a single layer of cholangiocytes, containing pus and bile in its lumen and surrounded by granulation tissue. An accumulation of neutrophils in the lumen of the bile ducts was observed, as well as an infiltration of the ducts and cysts surrounding connective tissue by CD4+ and to a lesser extent CD8+ lymphocytes. This may be caused by the expression of HLA-DR by cholangiocytes. Atrophy and desquamation of the epithelium of collecting tubules with the formation of microcysts were detected in the kidneys without a clinically significant loss of renal function. Morphopathogenetic mechanisms of the Caroli syndrome can be targets for a potential pathogenetic therapy and prevention of its manifestations and complications.


Assuntos
Doença de Caroli/patologia , Adulto , Atrofia , Ductos Biliares Intra-Hepáticos/patologia , Doença de Caroli/genética , Dilatação Patológica , Epitélio/patologia , Humanos , Túbulos Renais/patologia , Fígado/patologia , Masculino , Mutação de Sentido Incorreto , Receptores de Superfície Celular/genética
4.
Medicine (Baltimore) ; 97(50): e13531, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558011

RESUMO

RATIONALE: Ciliopathies is a group of clinically and genetically overlapping disorders due to cilia abnormalities and multiple organ systems are involved in. PATIENT CONCERNS: We present a young female patient who showed renal function impairment, Caroli syndrome (CS), liver cirrhosis, polycystic ovarian syndrome, and multiple subcutaneous cysts. DIAGNOSES: The patient was diagnosed with ciliopathy according to the clinical manifestations and whole-genome sequencing. INTERVENTIONS: She received treatment of intravenous albumin, polyene phosphatidyl choline, furosemide, and antisterone. OUTCOMES: The patient showed clinical improvement in her edema and liver tests, and ultrasonography revealed that the ascites had disappeared. Unfortunately, the edema relapsed a year later. The patient received the same treatment as before, and there was clinical improvement of the edema. Since the family cannot afford liver and kidney transplantation, the patient only accepted symptomatic treatment. LESSONS: Polycystic ovarian syndrome and multiple subcutaneous cysts have never before been reported to be associated with ciliopathy. This finding could remind doctors to consider the possibility of ciliopathy disease for patients suffering from similar conditions. In addition, the phenotype of the patient differs from those of patients reported with the same mutations, which also reminds doctors that the clinical manifestation of a given mutation may show patient-specific differences. This case report extends the phenotypic spectrum of ciliopathy, and these findings might represent a new ciliopathy syndrome, which could facilitate the diagnosis of ciliopathies.


Assuntos
Doença de Caroli/genética , Ciliopatias/genética , Doenças Renais Císticas/genética , Cirrose Hepática/genética , Síndrome do Ovário Policístico/genética , Adolescente , Doença de Caroli/complicações , Ciliopatias/complicações , Feminino , Humanos , Doenças Renais Císticas/complicações , Cirrose Hepática/complicações , Mutação , Fenótipo , Síndrome do Ovário Policístico/complicações
5.
Beijing Da Xue Xue Bao Yi Xue Ban ; 50(2): 335-339, 2018 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-29643536

RESUMO

This case report is about one genetically specified diagnosed infant case of Caroli syndrome with autosomal recessive polycystic kidney disease (ARPKD) in China. The patient in this case report was an eight-month infant boy with an atypical onset and the main clinical manifestation was non-symptomatic enlargement of the liver and kidneys. The imaging study demonstrated a diffused cystic dilatation of intrahepatic bile ducts as well as polycystic changes in bilateral kidneys. The basic blood biochemical tests indicated a normal hepatorenal function. Four serum biomarkers of hepatic fibrosis were all elevated and the urine test for an early detection of the renal injury was positive. The genetic sequencing proved two heterozygous missense mutations of polycystic kidney and hepatic disease 1 (PKHD1) gene, c.9292G>A and c.2507T>C, inherited from each of his parents respectively. The former was a novel mutation that had been verified as disease causing through the predicting software while the latter had been reported from one recent case study on Chinese twins, which was possibly unique among Chinese population. The relations between the gene type and the clinical phenotype were not clarified yet. Up till a follow-up eleven months later after the discharge, the patient had a normal hepatorenal function without occurrence of any severe complication yet. The clinical symptoms of Caroli syndrome with ARPKD at infant stage were atypical and the enlargement of liver and kidney was usually the sole symptom. From the above systematic retrospective clinical analysis, as well as the relevant literature review, it's been concluded that the features of the hepatorenal images in patients with Caroli syndrome and ARPKD were distinctive. Genetic testing combined with the imaging study benefits a definite diagnosis as well as a differentiation from other hepatorenal fibrocystic diseases. Specific to the long-term management of this kind of patients, it's necessary to schedule a regular follow-up to monitor the hepatorenal function and the occurrence of various complications for an appropriate intervention, meantime to devote efforts to the genetic counseling work for the patients' family.


Assuntos
Doença de Caroli/diagnóstico , Rim Policístico Autossômico Recessivo/diagnóstico , Grupo com Ancestrais do Continente Asiático , Ductos Biliares Intra-Hepáticos , Doença de Caroli/genética , China , Testes Genéticos , Heterozigoto , Humanos , Lactente , Rim , Cirrose Hepática , Masculino , Mutação de Sentido Incorreto , Fenótipo , Rim Policístico Autossômico Recessivo/genética , Receptores de Superfície Celular/genética , Estudos Retrospectivos
6.
Diagn Pathol ; 12(1): 61, 2017 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-28814334

RESUMO

BACKGROUND: Abernethy malformation is a rare congenital anomaly characterised by the partial or complete absence of the portal vein and the subsequent development of an extrahepatic portosystemic shunt. Caroli's disease is a rare congenital condition characterised by non-obstructive saccular intrahepatic bile duct dilation. Caroli's disease combined with congenital hepatic fibrosis and/or renal cystic disease is referred to - Caroli's syndrome. The combination of Abernethy malformation and Caroli's syndrome has not been reported previously. CASE PRESENTATION: We present the case of a 23-year-old female who was found to have both type II Abernethy malformation and Caroli's syndrome. Radiological imaging was performed, including computed tomography with three-dimensional reconstruction and magnetic resonance imaging with (magnetic resonance cholangiopancreatography (MRCP), which revealed a side-to-side portocaval shunt, intrahepatic bile duct dilation, congenital hepatic fibrosis, and renal cysts. In addition, PKHD1 (polycystic kidney and hepatic disease 1) gene mutational analysis revealed a paternally inherited heterozygous missense mutation (c.1877A > G, p.Lys626Arg). A liver biopsy confirmed the pathological features of Caroli's syndrome. CONCLUSIONS: To our knowledge, this is the first reported case of a patient with both type II Abernethy malformation and Caroli's syndrome diagnosed using a comprehensive approach that included imaging, mutational analysis, and liver biopsy. Additionally, this is the second reported case to date of an Asian patient presenting with liver and renal disorders with the same paternally inherited PKHD1 missense mutation.


Assuntos
Doença de Caroli/complicações , Doença de Caroli/genética , Veia Porta/anormalidades , Receptores de Superfície Celular/genética , Malformações Vasculares/complicações , Malformações Vasculares/genética , Feminino , Humanos , Mutação , Adulto Jovem
7.
Pediatr Nephrol ; 31(1): 113-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26260382

RESUMO

BACKGROUND: Hepatorenal fibrocystic diseases (HRFCDs) are a group of monogenic disorders characterized by developmental abnormalities involving the liver and kidney. In this study, we performed genotype and phenotype analyses of children with HRFCDs to determine the distribution of underlying diseases. METHODS: A total of 36 children with HRFCDs were recruited, with genetic tests being performed in 22 patients and 14 patients diagnosed clinically as having autosomal recessive polycystic kidney disease (ARPKD). RESULTS: In children with HRFCDs, ARPKD was the most common disease, found in 16/36 (44.4 %), followed by nephronophthisis 13 (NPHP13) in 11/36 (30.6 %) and Meckel-Gruber syndrome type 3 (MKS3) in 4/36 (11.1 %). Renal function deteriorated faster in children with NPHP13. The main hepatic pathology was Caroli disease in the NPHP13 patients, while most other patients had Caroli syndrome or congenital hepatic fibrosis. Of note, three of four MKS3 patients had an accompanying choledochal cyst. No ARPKD patient had other organ involvement, while several NPHP13 patients had ocular and/or neurodevelopmental involvement. In contrast, all MKS3 patients had severe ocular and neurodevelopmental involvement. CONCLUSIONS: NPHP13 is a major disease in the HRFCD category, and thorough evaluation of its clinical features, including kidney, liver and other organ involvement, may aid in the differential diagnosis of HRFCD.


Assuntos
Doença de Caroli/epidemiologia , Transtornos da Motilidade Ciliar/epidemiologia , Encefalocele/epidemiologia , Doenças Genéticas Inatas/epidemiologia , Cirrose Hepática/epidemiologia , Doenças Renais Policísticas/epidemiologia , Rim Policístico Autossômico Recessivo/epidemiologia , Adolescente , Adulto , Fatores Etários , Doença de Caroli/diagnóstico , Doença de Caroli/genética , Criança , Pré-Escolar , Transtornos da Motilidade Ciliar/diagnóstico , Transtornos da Motilidade Ciliar/genética , Encefalocele/diagnóstico , Encefalocele/genética , Feminino , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Predisposição Genética para Doença , Testes Genéticos , Humanos , Lactente , Falência Renal Crônica/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Masculino , Fenótipo , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/genética , Rim Policístico Autossômico Recessivo/diagnóstico , Rim Policístico Autossômico Recessivo/genética , Valor Preditivo dos Testes , Prognóstico , Insuficiência Renal Crônica/epidemiologia , República da Coreia/epidemiologia , Fatores de Risco , Adulto Jovem
8.
Pediatr Nephrol ; 30(9): 1451-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25726036

RESUMO

BACKGROUND: Nephronophthisis 13 (NPHP 13) is associated with mutations in the WDR19 gene, which encodes for a protein in the intraflagellar transport complex. Herein, we describe six additional cases accompanied by Caroli syndrome or disease. METHODS: Targeted exome sequencing covering 96 ciliopathy-related genes was performed for 48 unrelated Korean patients with a clinical suspicion of NPHP. Mutations were confirmed by Sanger sequencing. We evaluated the expression of WDR19 in the biopsied kidney by immunohistochemistry in patients and controls. RESULTS: We detected three (3/48, 6.3 %) unrelated index cases with WDR19 mutations. One of the cases involved two siblings with the same mutation. Later, we detected an additional index case with a similar phenotype of kidney and liver involvement by Sanger sequencing of WDR19. The p.R1178Q mutation was common in all patients. All of the six affected patients from four families progressed to chronic kidney disease. Of note, all six patients had Caroli syndrome or disease. Immunohistochemistry for WDR19 showed localized expression along the luminal borders of the renal tubular epithelium in controls, whereas it showed diffuse cytoplasmic staining in the affected patients. CONCLUSIONS: Caroli disease is a major extra-renal phenotype associated with mutations in WDR19 in the Korean population. In this study, we visually validated the expression pattern of mutant WDR19 protein in the kidneys of NPHP 13 patients. More data are needed to identify the true frequency of p.R1178Q. Functional studies including transfection assay will provide solid grounds for the pathogenicity of each mutation.


Assuntos
Doença de Caroli , Rim/patologia , Rim Policístico Autossômico Recessivo , Proteínas/genética , Adolescente , Doença de Caroli/diagnóstico , Doença de Caroli/genética , Criança , Proteínas do Citoesqueleto , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Mutação , Rim Policístico Autossômico Recessivo/diagnóstico , Rim Policístico Autossômico Recessivo/genética , Sequências Repetitivas de Aminoácidos/genética , República da Coreia , Adulto Jovem
9.
Rev. cientif. cienc. med ; 18(2): 53-56, 2015. ilus
Artigo em Espanhol | LILACS | ID: lil-785623

RESUMO

La enfermedad de Caroli es una condición congénita poco frecuente, cuya incidencia se estima en 1 caso por millón. Se caracteriza por dilataciones saculares o fusiformes de las vías biliares. Entre las manifestaciones clínicas se encuentran dolor en hipocondrio derecho, fiebre e ictericia, estas crisis de colangitis secundarias a estasis biliar, y sepsis. Su diagnóstico se basa en el hallazgo de lesiones quísticas en árbol biliar, pueden observarse por ecografía, tomografía computarizada. Presentamos a paciente femenino de 37 años, acude a emergencia de Medicina Interna del Hospital Escuela, de la ciudad deTegucigalpa, Honduras, manifestando signos y síntomas de colangitis aguda e ictericia. Al examen físico presenta abdomen globoso y doloroso a expensas de una hepatomegalia marcada. Nuestra paciente presento episodios de colangitis recurrente. La tomografía computarizada revela múltiples espacios quísticos en ambos lóbulos hepáticos y se encontró lesiones quísticas en el árbol biliar. Excluyendo, colangitis esclerosante, quiste hidatídico, quiste del colédoco y dilatación ductal hereditaria, y confirmando la sospecha diagnostica de enfermedad de Caroli.


Caroli disease is a rare congenital condition, which incidence is estimated at 1 case per million. Characterized by saccular or fusiform dilation of the bile. Clinical manifestations include right upper quadrant pain, fever and jaundice, these crisis of cholangitis are secondary to biliary stasis, and sepsis. Diagnosis is based on the discovery of cystic lesions in biliary tree, it may be seen by ultrasound, computed tomography. We present a case of female patient with 37-year-old, who attends to the emergency service of internal medicine of the Hospital Escuela Universitario of the city ofTegucigalpa, Honduras, manifesting signs and symptoms of acute cholangitis and jaundice. Physical examination reveals globose and painful abdomen at the expense of a marked he-patomegaly. Our patient presented episodes of recurrent cholangitis, the computed tomography reveals multiple cystic spaces in both lobes and was found lesions in the biliary tree. Excluding, sclerosing cholangitis, hydatid cyst, bile duct and hereditary ductal dilatation, and confirmed the suspected diagnosis of Caroli's disease.


Assuntos
Humanos , Feminino , Adulto , Doença de Caroli/genética , Cuidados Paliativos/métodos , Colangiografia/métodos
10.
Saudi J Kidney Dis Transpl ; 25(4): 840-3, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24969198

RESUMO

Caroli's syndrome (CS) is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow-up for monitoring the progression of the disease. In conclusion, patients with CS should be screened for renal cystic lesions and vice versa even if they are asymptomatic. Also, as the disease is inherited in an autosomal recessive manner, it is important to screen family members for early diagnosis and management.


Assuntos
Doença de Caroli/complicações , Rim Policístico Autossômico Recessivo/complicações , Doença de Caroli/diagnóstico , Doença de Caroli/genética , Doença de Caroli/terapia , Criança , Progressão da Doença , Feminino , Predisposição Genética para Doença , Testes Genéticos , Hereditariedade , Humanos , Lactente , Masculino , Linhagem , Fenótipo , Rim Policístico Autossômico Recessivo/diagnóstico , Rim Policístico Autossômico Recessivo/genética , Rim Policístico Autossômico Recessivo/terapia , Prognóstico , Irmãos , Tomografia Computadorizada por Raios X
11.
Hum Genet ; 132(8): 865-84, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23559409

RESUMO

Nephronophthisis-related ciliopathies (NPHP-RC) are autosomal-recessive cystic kidney diseases. More than 13 genes are implicated in its pathogenesis to date, accounting for only 40 % of all cases. High-throughput mutation screenings of large patient cohorts represent a powerful tool for diagnostics and identification of novel NPHP genes. We here performed a new high-throughput mutation analysis method to study 13 established NPHP genes (NPHP1-NPHP13) in a worldwide cohort of 1,056 patients diagnosed with NPHP-RC. We first applied multiplexed PCR-based amplification using Fluidigm Access-Array™ technology followed by barcoding and next-generation resequencing on an Illumina platform. As a result, we established the molecular diagnosis in 127/1,056 independent individuals (12.0 %) and identified a single heterozygous truncating mutation in an additional 31 individuals (2.9 %). Altogether, we detected 159 different mutations in 11 out of 13 different NPHP genes, 99 of which were novel. Phenotypically most remarkable were two patients with truncating mutations in INVS/NPHP2 who did not present as infants and did not exhibit extrarenal manifestations. In addition, we present the first case of Caroli disease due to mutations in WDR19/NPHP13 and the second case ever with a recessive mutation in GLIS2/NPHP7. This study represents the most comprehensive mutation analysis in NPHP-RC patients, identifying the largest number of novel mutations in a single study worldwide.


Assuntos
Doença de Caroli/genética , Cílios/genética , Cílios/patologia , Genes Recessivos/genética , Doenças Renais Císticas/genética , Proteínas de Membrana/genética , Mutação/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Doença de Caroli/patologia , Estudos de Coortes , Proteínas do Citoesqueleto , Análise Mutacional de DNA , Feminino , Saúde Global , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Renais Císticas/patologia , Masculino , Reação em Cadeia da Polimerase Multiplex , Linhagem , Projetos Piloto
12.
Eur J Pediatr ; 172(7): 877-81, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21845392

RESUMO

UNLABELLED: We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. CONCLUSION: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.


Assuntos
Anormalidades Múltiplas/genética , Doença de Caroli/genética , Anormalidades Craniofaciais/genética , Cinesina/genética , Rim Policístico Autossômico Recessivo/genética , Polidactilia/genética , Situs Inversus/genética , Anormalidades Múltiplas/cirurgia , Doença de Caroli/patologia , Pré-Escolar , Feminino , Humanos , Transplante de Rim , Transplante de Fígado , Mutação , Rim Policístico Autossômico Recessivo/patologia
13.
Histol Histopathol ; 25(2): 223-35, 2010 02.
Artigo em Inglês | MEDLINE | ID: mdl-20017109

RESUMO

Recent progress in elucidating the etiopathogenesis of pediatric biliary diseases, particularly Caroli's disease with congenital hepatic fibrosis (CHF) and biliary atresia (BA), is reviewed. The former is characterized by multiple saccular dilatations of the intrahepatic bile ducts. An animal model of this disease, the PCK rat, is being extensively studied. PCK rats and Calori's disease with CHF belong to autosomal recessive polycystic kidney disease (ARPKD) with ductal plate malformation. Mutations of PKHD1 have been identified in ARPKD, and fibrocystin, a product of PKHD1 located in the cilia of bile ducts is lacking in the pathologic intrahepatic bile ducts of ARPKD. Disordered cell kinetics, including apoptosis of biliary epithelial cells (BECs), may be significantly related to ductal plate malformation, and laminin and type IV collagen were immunohistochemically reduced in the basement membrane of intrahepatic bile ducts of ARPKD, and such a reduction is an additional factor for the dilatation of bile ducts. Abundant connective tissue growth factor retained diffusely in heparan sulfate proteoglycan in the fibrous portal tracts are responsible for non-resolving hepatic fibrosis. In addition, pathologic BECs of ARPKD may acquire mesenchymal features and participate in progressive hepatic fibrosis by producing extracellular matrix molecules. In an animal model of BA, an initial virus-induced, T-cell mediated autoimmune-mediated cholangiopathy has been reported. In human BA, virus-induced apoptosis of BECs by a TNF-related apoptosis-inducing ligand followed by the progressive obliteration of bile ducts is also suggested, and epithelial mesenchymal transition of BECs induced by viral infection may be involved in the fibrotic process in sclerosing cholangitis. However, the role of viral infections in the affected tissues is controversial. Comprehensive and analytical studies of ARPKD and BA using human materials and animal models may lead to the clarification of their etiopathogenesis and open the way for new therapeutic strategies.


Assuntos
Ductos Biliares Intra-Hepáticos/anormalidades , Atresia Biliar/genética , Doença de Caroli/genética , Cirrose Hepática/congênito , Imunidade Adaptativa , Animais , Ductos Biliares Intra-Hepáticos/imunologia , Ductos Biliares Intra-Hepáticos/metabolismo , Atresia Biliar/imunologia , Atresia Biliar/metabolismo , Atresia Biliar/patologia , Doença de Caroli/imunologia , Doença de Caroli/metabolismo , Doença de Caroli/patologia , Dilatação Patológica , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Predisposição Genética para Doença , Humanos , Imunidade Inata , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Mutação , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/patologia , Ratos , Fatores de Risco , Linfócitos T/imunologia , Viroses/imunologia
15.
Curr Gastroenterol Rep ; 9(2): 151-5, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17418061

RESUMO

Caroli's disease is a rare congenital disease of the liver characterized by cystic dilation of the intrahepatic bile duct. Classic Caroli's disease involves malformations of the biliary tract alone, whereas Caroli's syndrome refers to the presence of associated congenital hepatic fibrosis. Caroli's disease usually presents during childhood and early adulthood. The clinical features of Caroli's disease include jaundice, right upper abdominal pain, and fever due to the associated complications of hepatolithiasis or bacterial cholangitis. Endoscopic or percutaneous cholangiography is the traditional method of diagnosis, but magnetic resonance cholangiopancreatography is emerging as the diagnostic modality of choice. The treatment for Caroli's disease includes supportive care with antibiotics for cholangitis and ursodeoxycholic acid for hepatolithiasis. Surgical resection has been used successfully in patients with monolobar disease. For patients with diffuse involvement, the treatment of choice is orthotopic liver transplantation.


Assuntos
Doença de Caroli/diagnóstico , Doença de Caroli/terapia , Doença de Caroli/complicações , Doença de Caroli/genética , Colagogos e Coleréticos/uso terapêutico , Colangiopancreatografia por Ressonância Magnética , Colangite/etiologia , Humanos , Hipertensão Portal/complicações , Transplante de Fígado , Ácido Ursodesoxicólico/uso terapêutico
16.
Clin Liver Dis ; 10(1): 55-71, v-vi, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16376794

RESUMO

The hepatic fibrocystic diseases present with variable intrahepatic biliary abnormalities, which range from portal tract enlargement and fibrosis to cystic formations. They may present as autosomal recessive or dominant polycystic kidney diseases, with associated dilatation of the renal collecting system, or as incompletely characterized cystic diseases. Symptoms from the liver disease often result from complications of fibrosis or dilated ducts/cyst (sludge, lithiasis, infection). The treatment is supportive, with careful attention to associated renal disease. Liver transplantation is an option in selected patients.


Assuntos
Doença de Caroli/genética , Cistos/genética , Hepatopatias/genética , Doenças Renais Policísticas/genética , Doença de Caroli/complicações , Cisto do Colédoco/complicações , Cisto do Colédoco/genética , Cistos/complicações , Humanos , Hepatopatias/complicações , Doenças Renais Policísticas/complicações
17.
Gastroenterol Clin Biol ; 29(8-9): 861-9, 2005.
Artigo em Francês | MEDLINE | ID: mdl-16294159

RESUMO

In 50% of cases, polycystic liver disease is associated with autosomal dominant polycystic kidney disease, which is caused by mutations in the PKD1 and PKD2 genes that encode polycystin-1 and -2, respectively. These proteins form a polycystin-1/2 complex on the plasma membrane, including that localized on the surface of primary cilia, where they act as mechanosensors. Polycystin-1 acts as a (mechano)receptor of environmental signals, and polycystin-2 as a calcium channel mediating intracellular transduction. Isolated autosomal dominant polycystic liver disease is caused by mutations in PRKCSH that encodes hepatocystin, a protein of the endoplasmic reticulum, which may participate in the N-glycosylation and maturation of proteins addressed to the cell surface. Congenital hepatic fibrosis whether it is accompanied by bile duct dilatations (Caroli's syndrome) or not, may be associated with autosomal recessive polycystic kidney disease, which is caused by mutations in PKHD1 that encodes fibrocystin, a protein of primary cilia. Genetic defects in fibrocystin cause ciliary dysfunction, presently considered as a major pathogenic event in cystogenesis. Excessive cell proliferation, a hallmark of cystic biliary epithelium, occurs in combination with deregulation of the epidermal growth factor (EGF) and probably also estrogen receptors. EGF receptor antagonists inhibit kidney and liver cyst development in animal models, and are currently under investigation in phase I and II clinical trials in patients with autosomal dominant polycystic kidney disease.


Assuntos
Cistos/genética , Hepatopatias/genética , Doença de Caroli/tratamento farmacológico , Doença de Caroli/genética , Cistos/tratamento farmacológico , Humanos , Hepatopatias/congênito , Hepatopatias/tratamento farmacológico , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/genética , Relação Estrutura-Atividade , Canais de Cátion TRPP/química
18.
J Pediatr Endocrinol Metab ; 18(3): 315-8, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15813611

RESUMO

Autosomal recessive polycystic kidney disease (ARPKD) is an important renal disease of childhood. Congenital hypothyroidism has been associated with glomerulocystic kidney disease, but to date no association has been made with ARPKD. To our knowledge this is the first reported case of congenital hypothyroidism in an infant with ARPKD.


Assuntos
Doença de Caroli/complicações , Doença de Caroli/genética , Hipotireoidismo Congênito , Hipotireoidismo/etiologia , Rim Policístico Autossômico Recessivo/complicações , Rim Policístico Autossômico Recessivo/genética , Feminino , Humanos , Recém-Nascido
19.
Am J Pathol ; 166(1): 49-60, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15631999

RESUMO

Polycystic kidney (PCK) rats exhibit a multiorgan cyst pathology similar to human autosomal recessive polycystic kidney disease, and are proposed as an animal model of Caroli's disease with congenital hepatic fibrosis (CHF). This study investigated the expression and function of selected components of the mitogen activated protein kinase (MAPK) pathway in cultured intrahepatic biliary epithelial cells (BECs) of PCK rats. Compared to the proliferative activity of cultured BECs of control rats, those of the PCK rats were hyperresponsive to epidermal growth factor (EGF). The increase in BEC proliferation was accompanied by overexpression of MAPK/extracellular signal-regulated protein kinase (ERK) kinase 5 (MEK5), and subsequent phosphorylation of ERK5 in vitro. The increased proliferative activity was significantly inhibited by the transfection of short interfering RNA against MEK5 mRNA. An EGF receptor tyrosine kinase inhibitor, gefitinib ("Iressa", ZD1839), also significantly inhibited the abnormal growth of cultured BECs of PCK rats. By contrast, treatment with PD98059 and U0126, inhibitors for MEK1/2, was less effective. These results suggest that the activation of the MEK5-ERK5 cascade plays a pivotal role in the biliary dysgenesis of PCK rats, and also provide insights into the pathogenesis of Caroli's disease with CHF. As the MEK5-ERK5 interaction is highly specific, it may represent a potential target of therapy.


Assuntos
Doença de Caroli/patologia , MAP Quinase Quinase 5/genética , Proteína Quinase 7 Ativada por Mitógeno/genética , Doenças Renais Policísticas/enzimologia , Animais , Ductos Biliares Intra-Hepáticos , Doença de Caroli/enzimologia , Doença de Caroli/genética , Divisão Celular , Células Cultivadas , Primers do DNA , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/genética , MAP Quinase Quinase 5/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos
20.
Ultrasound Obstet Gynecol ; 23(1): 73-6, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14971004

RESUMO

Caroli's disease is a rare autosomal recessive condition characterized by cystic dilatation of the intrahepatic bile ducts and infantile polycystic kidney disease. We report a case with Caroli's disease detected prenatally at 33 weeks' gestation with fetal ultrasound findings of a cystic liver mass and echogenic kidneys. Postnatal investigation confirmed enlarged and echogenic kidneys with dilatation of the intrahepatic bile ducts consistent with the diagnosis of Caroli's disease. Genetic analysis of the gene, PKHD1, associated with autosomal recessive polycystic kidney disease (ARPKD) showed that the patient had compound heterozygous mutations, confirming that this early onset Caroli's disease was part of the spectrum of ARPKD. To our knowledge this is the third case of Caroli's disease detected prenatally and the first in which the infant survived.


Assuntos
Doença de Caroli/diagnóstico por imagem , Ultrassonografia Pré-Natal , Doença de Caroli/genética , Feminino , Testes Genéticos/métodos , Heterozigoto , Humanos , Recém-Nascido , Masculino , Mutação/genética , Gravidez , Resultado da Gravidez , Receptores de Superfície Celular/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...