PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS 2 (PFIC2)
ABCB11 Sequencing
MITOCHONDRIAL DNA ANALYSIS
Also known as: Benign Recurrent Intrahepatic Cholestasis 2 (BRIC2); Bile Salt Excretory Pump Disease (BSEP)

Description:

The ABCB11 gene product resides in the hepatocyte canalicular membrane and is the main transporter of conjugated bile acids into bile. Patients with impaired function of ABCB11 have markedly low levels of bile acids in bile, leading to hepatocytic retention of bile acids, and subsequent progressive resultant hepatocellular damage, often in infancy and early childhood. Impaired function of ABCB11 is associated with severe nutritional consequences, including deficiencies of fat-soluble vitamins. Progressive familial intrahepatic cholestasis2 (PFIC2, OMIM #601847) is a chronic autosomal recessive disorder due to impaired function, or mutations of the ABCB11 gene, causing hepatomegaly, cholestasis, pruritus, hepatic fibrosis, cirrhosis, and a potential predisposition to liver cancer. Heterozygous individuals may suffer from intermittent bouts of cholestasis, pruritus, and diarrhea, a condition known as benign recurrent intrahepatic cholestasis (BRIC). A principal confounder to PFIC2 is PFIC1, deficiency of ATP8B1 (test # 3305) since both disorders lead to hepatocellular bile acid retention, lab tests notable for high serum bile acids with low/normal levels of gamma-glutamyltranspeptidase (low GGT cholestasis), and mutations of either gene can lead to clinical features of BRIC. PFIC1 patients may have features of extrahepatic disease--diarrhea, failure to thrive, pancreatitis, deafness, which is not seen in PFIC2 patients. Histological findings note hepatocellular cholestasis, giant cell transformation, and progression of fibrosis and cirrhosis. Many patients with mutations in ABCB11 require close attention to nutrition and liver function, since they may ultimately require consideration for supplementation, biliary diversion, or liver transplantation.

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing

Testing Methodology:

The exons and flanking intron regions of ABCB11 gene are PCR amplified and sequenced.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc

Turnaround Time:

5 weeks

CPT Codes and Prices:

Index: 83891, 83898x27, 83904x54, 83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:

>> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included

References:

1. Thompson R and Strautnieks S (2001). BSEP: function and role in progressive familial intrahepatic cholestasis. Seminars in Liver Disease 21: 545-550.
2. Oude Elferink RP, Paulusma CC, Groen AK (2006). Hepatocanalicular transport defects: pathophysiologic mechanisms of rare diseases. Gastroenterology 130: 908-925.
3. Knisely AS, Strautnieks SS, Meier Y, Stieger B, Byrne JA, Portmann BC, Bull LN, et al (2006). Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Hepatology 44: 478-486.
4. Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, et al (1998). A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 20: 233-238.

Test Codes:

Index: 3310
Known Familial Mutation: 3311