| Condition
/ Diagnosis |
Gene
/ Product |
| Rotor Syndrome |
SLCO1B
gene on Chromosome 2q37 Encodes the transport protein OATP1B (reuptake of circulating bilirubin) AR |
| Dubin-Johnson Syndrome |
ABCC2
(previously MRP2) on Chomosome 10q24 Encodes the MRP2 transporter (Secretion of conjugated bilirubin into bile canaliculus) AR |
| Gilbert Syndrome |
Variety of mutations on UGT1A1 gene on Chomosome 2q37 Encodes UGT 1A1 bilirubin conjugating enzyme AR but can have missense mutation |
| Crigler-Najjar Syndrome |
UGT1A1
gene on Chomosome 2q37 Encodes UGT 1A1 bilirubin conjugating enzyme (Type I - totally absent) Mostly AR |
| Alagille Syndrome |
Jagged
1 gene on Chromosome 20 Encodes Jag1/Notch protein AD with variable penetrance |
| Progressive Familial
Intrahepatic Cholestasis 1 (PFIC) |
ATP8B1 Gene on Chromosome 18q21-22 encodes FIC1 protein Low GGT, Coarse granular "Byler Bile" on electron microscopy Same Gene/Protein defect in BRIC1 and Greenland familial cholestasis (GFC) AR |
| Progressive Familial
Intrahepatic Cholestasis 2 |
BSEP
(ABCB11) Gene on Chromosome 2q24 Low GGT, neonatal giant cell hepatitis and amorphous canalicular bile on EM Risk of HCC or cholangiocarcinoma AR |
| Progressive Familial
Intrahepatic Cholestasis 3 |
MDR3
(ABCB4) Gene on Chromosome 7q21 High GGT, bile duct proliferation and periportal bile on EM AR |
| PFIC Associated gene |
Gene TJP2 on Chromosome 9q2 Early onset cholestasis with severe liver disease - end stage before adulthood AR |
| Benign Recurrent Intrahepatic
Cholestasis (BRIC) |
Gene ATP8B1 on chromosome 18q21-31 (BRIC type 1) and gene ABCB1/BSEP on chromosome 2q24 (Bric type 2) normal GGT; intermittent, recurrent cholestasis asymptomatic between episodes AR |
| Δ 4 -3-Oxosteroid-5β
- reductase deficiency |
Gene AKR1D1 encodes 5β - reductase protein Bile Acid synthetic defect - Neonatal cholestasis with giant cell hepatitis |
| 3β - hydroxy-5-C27-steroid oxidoreductase / dehydrogenase/ isomerase deficiency ( 3βHSD ) | **Most Common Bile Acid Defect
reported** Gene HSD3B7 encodes C27- 3β-HSD protein H/o consanguinity common, Tx with Cholbam (Cholic acid) |
| Oxysterol 7α - hydroxylase
deficiency |
Gene CYP7BI encodes CYP7BI protein which
regulates acidic pathway of bile acid synthesis 5 cases reported |
| BAAT deficiency ---------------------------------- Familial hypercholanemia (FHCA) |
Gene BAAT encodes BAAT protein/enzyme
which transfers bile acid moiety from the acyl coenzyme A thioester to
either glycine or taurine ------------------------ FHCA1 - Gene TJP2 on Chromosome 9q21.11 ; elevated concentrations of bile acids (usually conjugated) FHCA2 - Gene SLC10A1 on chromosome 14q24 ;
|
| Farnesoid X receptor (FXR)
deficiency |
Gene NR1H4 encodes nuclear hormone
receptor (Fernesoid X receptor) FXR regulates bile acid metabolism by sensing levels of bile acids. When elevated, FXR will inhibit/repress bile acid synthesis |
| α -methylacyl-coenzyme A (CoA) racemase deficiency |
|
| Wilson Disease |
Gene ATP7B on chromosome 13q14.3
encoding ATP7B (P-type ATPase copper export pump) |
| Autosomal Dominant Polycystic
Kidney Disease ADPKD |
Gene PKD1 on Chromosome 16p13.3 Encodes
PKD1 Note - there are other forms (PKD1 through PKD7 all caused by different mutations) |
| Autosomal Recessive polycystic
kidney disease ARPKD |
Gene PKHD1 encodes Fibrocystin (ciliary
function and tubulogenesis) |
| Autosomal Dominant Polycystic
Liver Disease ADPLD |
Gene PRKCSH encodes Hepatocystin |
| Aagenaes Syndrome |
Chromosome 15q Recurrent cholestasis and lymphedema AR |