Differences in presentation and progression between severe FIC1 and BSEP deficiencies

Abstract

Background & Aims-Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these 2 disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations.

Progressive Familial Intrahepatic Cholestasis (PFIC) in Indian Children: Clinical Spectrum and Outcome

“…17,18 As also seen in the present study, PFIC 3 presents relatively late with cholestatic symptoms developing in late infancy (1/3rd) to adolescent age group. 6 Median time lag in diagnosing PFIC was 13 months to 8 years which could be attributable to poor awareness of PFIC disease spectrum among paediatricians, late referral and diagnostic difficulty.…”

“…20 Implicating family screening, 40% of the patients of PFIC had an affected sibling or family member. Previous studies 17,18 have reported affected sibling in 15-25% of PFIC. Similar to the present study, another series 19 of 5 cases have reported all cases born at term with normal birth weight.…”

“…16,17 Growth faltering is prominent in PFIC and in part related to diminished luminal absorption of long-chain fatty acids. In 2 previous series, 17,18 growth failure was present in 71% and clinical evidence of vitamin D and K deficiency was found in 8-9%. More than half of our cases reported with rickets and/or coagulopathy.…”

Clinical utility gene card for: Progressive familial intrahepatic cholestasis type 2

“…[4][5][6][7][8] Mutations of ABCB11 can be found in the NHLBI ESP Exome Variant Server database (http://evs.gs.washington.edu/EVS/).…”

Clinical utility gene card for: Progressive familial intrahepatic cholestasis type 1

“…Large deletions and genomic rearrangements are also reported (10%). 3,[5][6][7][8] The majority of mutations are 'private' to specific families or ethnic communities. 5 Mutations of ATP8B1 can be found in the NHLBI ESP Exome Variant Server database (http://evs.gs.washington.edu/EVS/).…”