A treatable form of a potentially fatal liver disease
Bile acid synthesis disorders (BASD) due to single enzyme defects are a rare group of inherited genetic disorders caused by defects in the enzymes that make bile acids. These defects interfere with normal production of bile acids. As a result, bile cannot flow from the liver to the small intestine, a condition called cholestasis that presents as prolonged jaundice in newborns. Cholestasis occurs in about 1 in 2500 live births. BASD accounts for approximately 1%-3% percent of cholestatic jaundice cases.
What leads to an inability to make bile acids?
A mutation, or change in DNA, in any of the genes responsible for making the enzymes necessary for normal production of bile acids leads to a buildup of abnormal bile acids, which may be toxic to the liver. If left untreated, buildup of toxic bile acids may result in progressive liver disease.
What are bile acids and why are they important?
One of the primary functions of the liver is to produce bile and bile acids. Bile is a fluid that contains water, certain minerals, and other materials including bile acid, lipids, cholesterol, and an orange-yellow pigment (bilirubin). Bile helps with digestion and absorption of dietary fats, vitamins, and other nutrients and in the elimination of excess cholesterol, bilirubin, waste, and toxins from the body.
Bile acids are the key digestive components of bile. Cholic acid (KOE-lik AS-id) and chenodeoxycholic acid (KEE-noe-dee-OX-i-KOL-ik AS-id) are the primary bile acids produced by the liver. They enable the liver to work normally by:
- Promoting bile flow.
- Assisting with absorption of the fats and vitamins from the food we eat.
- Eliminating cholesterol from the body.
- Abnormal bile flow and bile production often result in malabsorption of vital nutrients and the accumulation of toxic materials in the body.
The cause of BASD
BASD is an inherited, genetic disorder, which means the disorder is passed down through the genes from parents.
In people with BASD, there is a mutation—or change—in the gene responsible for making the enzymes that are required to produce bile acids. Without normal production of bile acids, the liver can experience a buildup of abnormal bile acids. If left untreated, this toxic buildup can lead to progressive liver disease.
Symptoms of BASD
The most common sign of BASD is jaundice (a yellowish color to the skin or white part of the eyes) that lasts more than 2 weeks.
Other signs and symptoms include:
Poor growth (not meeting weight or height milestones for age)
Vitamin deficiencies (vitamins A, D, E, or K)
Pale, foul-smelling stools
Dark (tea-colored) urine
Enlarged liver or spleen
Elevated liver enzymes
If your child or loved one is exhibiting any of the symptoms mentioned above, it’s important for your child’s doctor to run tests in order to diagnose the cause. He or she will ask about your child’s medical history and complete a physical exam. Your doctor may perform blood and urine tests, including:
- Direct bilirubin
- Alanine transaminase (ALT)/aspartate transaminase (AST)
- Gamma glutamyltransferase (GGT)
- Primary bile acids
Your doctor can diagnosis BASD through genetic testing, which identifies mutations in genes that can cause cholestasis—a condition where bile flow is reduced or stopped. Learn more about no-cost testing for BASD.
Early diagnosis and treatment of BASD may lead to better outcomes
Early diagnosis and treatment are very important. BASD can cause liver damage and eventually the liver may no longer work normally and a liver transplant may be necessary. It is important to diagnose and treat BASD as early as possible, since untreated patients may develop serious liver disease or liver failure. Early identification and initiation of therapy may lead to better outcomes.
WHAT IS CHOLBAM® (cholic acid) capsules?
CHOLBAM is a prescription medicine. It is a bile acid used for
- Treatment of bile acid synthesis disorders (malfunction in the production of bile acid in the liver) due to a lack of a single enzyme responsible for bile acid production.
- Treatment (in addition to other treatments) of peroxisomal disorders (a loss of function in important parts of the cell), including Zellweger spectrum disorders, in patients who show signs or symptoms of liver disease, pale stools due to too much fat, or problems resulting from not absorbing certain vitamins (A, D, E, K).
The safety and effectiveness of CHOLBAM on symptoms outside of the liver have not been studied.
IMPORTANT SAFETY INFORMATION
CHOLBAM may not be right for you. Before taking CHOLBAM, tell your doctor about:
- All health conditions you may have and any medications you may be taking.
- If you are pregnant or plan to become pregnant.
- If you are breastfeeding or plan to breastfeed.
What are the possible side effects of CHOLBAM?
- Serious Side Effects: You will need to undergo laboratory testing periodically while on treatment to assess liver function. CHOLBAM may worsen liver function. Tell your doctor right away if you experience symptoms associated with worsening of liver function (e.g., skin or the whites of eyes turn yellow, urine turns dark or brown [tea colored], pain on the right side of stomach, bleeding or bruising occurs more easily than normal, or increased lethargy). Your doctor will decide if you need to discontinue treatment with CHOLBAM.
- Most Common Side Effects: Diarrhea, acid reflux that damages the lining of the esophagus, discomfort and fatigue, yellowing of skin or eyes, skin lesion, nausea, abdominal pain, formation of growths in the intestinal tract, urinary tract infection, nerve damage causing change in sensation in extremities.
These are not all the possible side effects of CHOLBAM. Tell your doctor if you have any side effect that bothers you or that does not go away.
You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Mirum Pharmaceuticals at 1-855-MRM-4YOU.
Please see accompanying full Prescribing Information for additional Important Safety Information.