Three distinct forms of familial intrahepatic cholestasis are the result of mutations in the ATP8B1, ABCB11, and ABCB4 genes. The pathophysiologies of the latter 2 of these diseases are well characterized and are the result of abnormalities in canalicular excretion of bile acids and phospholipids, respectively. The molecular pathophysiology of the systemic disease associated with mutations in ATP8B1 remains unclear. In all of these diseases, wide variations in clinical phenotypes have been observed. The variability can be ascribed at least in part to predicted genotype:phenotype correlations. Disease- and genotype-specific prognoses and therapeutic approaches may exist, although much more information needs to be ascertained before clinicians can confidently make decisions based on genetic information.
"In PFIC type 1 bland canalicular cholestasis with variable fibrosis is found. In PFIC type 2, variable features include canalicular cholestasis and a neonatal hepatitis pattern, with hepatocellular swelling and giant cell transformation. Immune staining is a useful diagnostic tool for PFIC type 2 since most patients with ABCB11 mutations and hepatobiliary disease of onset in infancy have no canalicular BSEP expression. "
[Show abstract][Hide abstract] ABSTRACT: Progressive familial intrahepatic cholestasis is an autosomal recessive liver disorder caused by (biallelic) mutations in the ATP8B1 of ABCB11 gene. A nine-year-old girl with cholestasis was referred for genetic counseling. She had a family history of cholestasis in two previous expired siblings. Genetic analysis of the ABCB11 gene led to the identification of a novel homozygous mutation in exon 25. The mutation 3593- A > G lead to a missense mutation at the amino acid level (His1198Arg). This mutation caused PFIC2 due to abnormal function in the bile salt export pump protein (BSEP).
Indian Journal of Human Genetics 07/2013; 19(3):366-8. DOI:10.4103/0971-6866.120813
"scarring well into adolescence . Few patients have survived into the third decade of life without treatment  . At present, the only curative treatment of PFIC is liver transplant  . "
[Show abstract][Hide abstract] ABSTRACT: Progressive familial intrahepatic cholestasis refers to a heterogenous group of autosomal recessive disorders in which children develop severe intrahepatic cholestasis progressing to biliary cirrhosis and chronic liver failure, usually during the first decade of life. The clinical features include jaundice, hepatomegaly, splenomegaly, growth retardation and severe pruritus. The laboratory tests demonstrate elevated bilirubin, bile acids and liver function enzymes. The only curative treatment of progressive familial intrahepatic cholestasis is liver transplantation.This article presents the medical and dental history along with a comprehensive dental management and prognosis of a 6 years old male patient with progressive familial intrahepatic cholestasis type I and liver cirrhosis 5 years post living related liver transplant in Riyadh, Saudi Arabia. The patient demonstrated improved oral hygiene performance during the course of treatment, and continued to demonstrate a low caries rate up to 7 months following treatment. Based upon the apparent success of the preventive programme, the patient was judged to have a very good prognosis.
[Show abstract][Hide abstract] ABSTRACT: Ginecol Obstet Mex 2012;80(4):285-294 Artículo de revisión RESUMEN La etiopatogenia de la colestasis intrahepática del embarazo incluye factores genéticos y ambientales. El hecho central de su fisiopatología es el incremento de los ácidos biliares en la sangre materna y fetal. Las altas concentraciones de esos ácidos causan prurito materno y alta morbilidad y mortalidad perinatal. La confirmación diagnóstica radica en la detección de ácidos biliares elevados en la sangre materna. El mejor tratamiento es el ácido ursodeoxicólico y, aunque es claro que abate las concentraciones de los ácidos biliares y el prurito, no lo es que disminuya la morbilidad y mortalidad perinatal. Los estudios hoy disponibles para la valoración del bienestar fetal no son útiles para predecir el riesgo de muerte del feto, pues parece claro que ésta ocurre debido a la hipoxia fetal aguda súbita. La medida más eficaz para abatir la tasa de óbitos en esta afección es la interrupción del embarazo entre las semanas 36 a 37. El objetivo de este escrito es presentar una revisión actualizada de la bibliografía relacionada con esta enfermedad. Palabras clave: colestasis, intrahepática, embarazo, óbito. ABSTRACT The etiology of intrahepatic cholestasis of pregnancy includes genetic and environmental factors. Bile acids elevation in maternal and fetal blood is the main fact of its physiopathology, causing maternal itching and high perinatal morbidity and mortality. High levels of maternal blood bile acids are diagnostic. Best treatment is ursodeoxycolic acid and clearly it produces amelioration of bile acid levels and itching, but it is uncertain if it reduces perinatal morbidity and mortality. As far as fetal death is one of sudden onset, probably due to acute hypoxia, tests to evaluate and predict fetal condition are useless. Pregnancy interruption at 36-37 gestation weeks is the best strategy for lowering fetal death incidence. The purpose of this work is to achieve an actualized literature review on this disease.
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