Liver, Pancreas, and Biliary TractHepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis☆,☆☆
Section snippets
Patients from the Groningen center
Patient A is a female born to nonconsanguineous parents who presented with neonatal cholestasis. In the first year of life, the serum alkaline phosphatase (ALP) activity was 393 U/L (normal [N] < 220 U/L), GGT 27 U/L (N < 45 U/L), total bilirubin 83 μmol/L (N < 17 μmol/L), conjugated bilirubin 54 μmol/L (N < 5 μmol/L), and serum bile salts 530 μmol/L (N < 9 μmol/L). The patient has 1 affected and 1 nonaffected sibling. At the age of 5 years, her serum bilirubin value was 48 μmol/L, conjugated
Characterization of BSEP antibodies
The rabbit polyclonal BSEP antibody detects a 170-kilodalton protein band in Western blots from canalicular enriched subfractions prepared from human, mouse, and rat liver (Figure 1). The molecular mass of BSEP has been reported to be 170 kilodaltons.14,
Discussion
PFIC is a heterogeneous group of diseases with various clinical manifestations and causes, including defects of hepatocanalicular transport of bile salts or phospholipids and defects of bile acid synthesis. Bile acid synthesis defects seem to be rare. The frequency of transport defects is not known, but this study shows that the combined cohorts of 3 liver transplantation centers yielded 28 patients with a PFIC phenotype with predominantly low serum GGT activity.
Liver samples from 16 of 28
Acknowledgements
The authors thank Micheline Dumont (INSERM, Hôpital Beaujon, Paris, France) for the bile salt analysis of the patients at Hôpital de Bicêtre, Paris, France; Gerard Dijkstra for his help with the photography; and Renze Boverhof (University Hospital Groningen) for the bile salt analysis of the patients in Groningen.
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2021, Annals of HepatologyCitation Excerpt :Unlike PFIC-1 (FIC1 deficiency), PFIC-2 (BSEP deficiency) and PFIC-4 (TJP2 deficiency), PFIC-5 (FXR deficiency) and MYO5B deficiency, PFIC-3 (MDR3 deficiency) patients rarely present with neonatal cholestatic jaundice; this more often occurs in late infancy, childhood, or even adulthood. Therefore, it is difficult to suspect this type of disease referred to as “cholestasis” in children who do not present with jaundice [5,12]. In a cohort of 427 patients with suspected genetic cholestasis, Dröge et al. (2017) observed that the median age of the onset of symptoms in PFIC-3 patients was later than in PFIC-1 or PFIC-2 patients [13].
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Address requests for reprints to: Peter L. M. Jansen, M.D., Division of Hepatology and Gastroenterology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. e-mail: [email protected]; fax: (31) 50-3619306.
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Supported by the Netherlands Organization for Scientific Research, NWO Program 902-23-191. E.J. and M.H. were supported by the Association Française contre les Myopathies, and the Assistance Publique-Hôpitaux de Paris (CRC no. 97001), Paris, France. R.J.T. is a Wellcome Advanced Fellow; S.S.S. is supported by grants from the Medical Research Council and the Children's Liver Disease Foundation.