SNP Shot: Genomic Insights

Progressive familial intrahepatic cholestasis (PFIC) is a genetic disorder causing progressive liver damage that usually ends in liver failure. In individuals with PFIC, liver cells have difficulty releasing bile, a digestive fluid. This bile accumulation within liver cells leads to liver disease.

The symptoms of PFIC generally appear in infancy and are a consequence of bile buildup and liver dysfunction. Common symptoms include intense itching, jaundice (yellowing of the skin and eyes), poor weight gain and growth (failure to thrive), elevated blood pressure in the portal vein (portal hypertension), and enlargement of the liver and spleen (hepatosplenomegaly).

There are three identified forms of PFIC: PFIC1, PFIC2, and PFIC3. These types can also be characterized by deficiencies in specific proteins crucial for healthy liver function. Each PFIC type is caused by a distinct genetic mutation.

Besides liver-related symptoms, individuals with PFIC1 may experience short height, hearing loss, diarrhea, inflammation of the pancreas (pancreatitis), and low blood levels of fat-soluble vitamins (A, D, E, and K). Liver failure typically occurs before adulthood in these cases.

PFIC2 symptoms are usually confined to liver problems, but these symptoms tend to be more pronounced than in PFIC1. Liver failure often occurs within the first few years of life for individuals with PFIC2. Furthermore, these individuals have a higher risk of developing hepatocellular carcinoma, a type of liver cancer.

Most individuals with PFIC3 exhibit symptoms related only to liver disease. PFIC3 symptoms typically manifest later in infancy or early childhood; in rare instances, diagnosis occurs in early adulthood. Liver failure can develop in childhood or adulthood in those with PFIC3.

Inheritance:

PFIC follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must have mutations for the condition to develop. Individuals with autosomal recessive conditions inherit one copy of the mutated gene from each parent, who are usually carriers and do not display symptoms themselves.