Effect of familial intrahepatic cholestasis type 1 on the nose potential difference response.

Familial intrahepatic cholestasis type 1 (FIC1) refers to a group of
autosomal-recessive familial liver disorders, characterized by intrahepatic
cholestasis due to mutations in the ATP8B1 gene. FIC1 disease comprises two
different disorders: progressive familial intrahepatic cholestasis type 1
(PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1). In
addition extrahepatic symptoms are described.
The exact mechanisms by which dysfunction of FIC1 cause cholestasis and
extrahepatic symptoms are currently unknown.
FIC is thought to play an important role in maintaining the asymmetry of the
phospholipid membrane, which is essential
for stability of the cell membrane and function of transmembrane-transporters.
One of these transmembrane-transporters is the cystic fibrosis transmembrane
regulator (CFTR). It is suggested that the CFTR function is compromised in FIC1
patients.
NPD measurements are sensitive to partial CFTR function and NPD is useful in
the diagnosis of classical and atypical cystic fibrosis (CF).
Here we would like to study the hypothesis that the NPD response is impaired in
patients with FIC1 deficiency.
The outcome of this study might help us to elucidate the function of FIC1 and
unravel the pathogenesis of FIC1 disease which may contribute in the
development of new therapy. In addition, NPD might be useful in monitoring the
effects of these possible future therapeutic approaches.

The aim of this study is to determine whether nose potential difference
response is impaired in patients with FIC1-deficiency.

Observational study with invasive measurements. No intervention.

We will approach approximately 10 patients diagnosed with BRIC1 and being
treated by gastro-enterologists in the UMC Urecht. We will ask them to
participate in our study.
The transepithelial nasal potential difference (NPD) will be measured in the
UMC Utrecht and takes approximately 2 hours.
A small catheter will be introduced into the nostril and the tip is positioned
onto the respiratory mucosa under the concha nasalis inferior. A reference
electrode will be placed in the subcutaneous space of the lower arm.
NPD measurements have shown to be useful in the diagnosis of classical and
atypical cystic fibrosis (CF) and no adverse effects have been reported so far.