Genetic Liver Diseases: Diagnosis And Treatment

Some liver diseases are hereditary. They are also called genetic liver diseases. That means they can be passed on from one generation to another, or you may have blood relatives with the same condition. 

Each one can have different complications and symptoms, so it's important to understand which type you have. 

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What is genetic liver disease? 

Genetic liver diseases are hereditary because they can be linked to specific genes and can be inherited. If you have inherited genes for liver disease, you are more likely, if not certain, to develop that disease. You may also pass those genes on to your children. 

It's not uncommon to see blood relatives with the same genetic disease. However, just because someone in your family has the disease doesn't necessarily mean that you will develop it, too; it depends on the disease.

Types of genetic liver diseases

There are numerous genetic liver diseases, but here are some of the more common or well-known ones. 


Hereditary hemochromatosis (HH) is a disorder characterized by a buildup of excessive amounts of iron in the body due to dysregulated dietary iron absorption. Iron has many vital roles in the body, such as being a key component of the protein transporting oxygen in the blood. 

However, with HH, excess iron accumulates in organs such as the liver, heart, and pancreas. 

When iron accumulates in the liver, it can damage the liver tissue. As a result, you can develop liver fibrosis, which can progress into cirrhosis and, ultimately, hepatocellular cancer (HCC). 

Most cases typically present with slow, nonspecific, and subtle symptoms such as fatigue. Upon further iron accumulation, typical presentations may include:

  • Joint pain 

  • Fatigue 

  • Weakness

  • Hypothyroidism 

  • Hypogonadism/erectile dysfunction 

Wilson disease 

Wilson disease is also known as copper storage disease or hepatolenticular degeneration. It's a rare but serious condition that prevents the body from clearing excess copper. 

The liver is responsible for releasing excess copper into the bile so it can be expelled from the body. However, in Wilson disease, copper doesn't get excreted in the bile. Instead, it accumulates in the body and causes damage to the brain, kidneys, and eyes. 

Wilson disease will affect the body from birth. But the symptoms may not present until sometime between the ages of 5 and 35. 

A vast range of symptoms is associated with Wilson disease because it can affect several areas of the body. 

Wilson disease can affect your:

  • Liver

  • Nervous system

  • Eyes 

  • Bones and joints 

  • Heart 

  • Kidneys 

  • Blood 

Wilson disease can cause both acute hepatitis and liver failure, as well as chronic hepatitis and cirrhosis. The symptoms associated with hepatic disease are: 

  • Fatigue 

  • Nausea

  • Pain in the upper right side of the abdomen 

  • Jaundice  (the skin and whites of the eyes appear yellow) 

Cystic fibrosis 

Cystic fibrosis is a genetic disease that affects exocrine glands, including the sweat glands and mucus glands. As a result of this disease, exocrine secretions become thick and sticky, causing several complications throughout the body. 

Cystic fibrosis mainly affects:

  • Lungs

  • Pancreas

  • Liver 

  • Intestines 

  • Sinuses 

  • Sex organs 

Mucus buildup in the bile ducts can hinder bile flow out of the liver, which can lead to liver inflammation and scarring. 

Alpha-1 antitrypsin deficiency 

Alpha-1 antitrypsin (AAT) is a protein made by the liver. It protects the lungs and other parts of the body from an enzyme secreted by neutrophils that breaks down tissues.  

Sometimes genetic mutations can cause the liver to make abnormal ATT proteins. These proteins can accumulate in the liver and cause problems. 

Signs and symptoms of AAT deficiency include: 

  • Shortness of breath on exertion

  • Wheezing 

  • Productive cough 

  • Fatigue 

  • Hepatomegaly 

  • Chest hyperinflation 

Gilbert syndrome 

Gilbert syndrome is a mild lifelong disorder characterized by nonhemolytic, unconjugated hyperbilirubinemia. Bilirubin is a breakdown product of the red blood cells. 

One of the liver's primary functions is to conjugate bilirubin for removal. This is dependent on an enzyme called UDPGT, and in those with Gilbert syndrome, this enzyme is not produced in sufficient levels.

People with Gilbert syndrome may experience jaundice, particularly during acute flare-ups brought on by physical or psychological stress. Jaundice is characterized by the yellowing of the whites of the eyes and skin. 

Gilbert syndrome does not cause symptoms nor cause chronic liver disease. Though, extremely rarely, some patients may have nonspecific complaints such as malaise, possibly related to high plasma bilirubin concentration. Treatment is unnecessary, and patients are reassured that they do not have liver disease.

Who is at risk of developing a genetic liver disease? 

Anyone who has inherited a genetic mutation or has a de novo mutation linked to liver disease is at risk of developing liver disease. However, some people are just carriers of the mutation, meaning that they have the potential to pass the disease on to their offspring, even if they never develop it themselves, depending on if the disease is autosomal dominant or recessive. 

If you have a close blood relative with a genetic liver disease, you may wish to get tested for the same condition. 

Genetic testing for liver disease

There are various tests available for testing genetic liver diseases. For example, various blood tests can help detect liver disease. 

Doctors can diagnose hemochromatosis by performing iron studies, including serum transferrin saturation and serum ferritin. Serum transferrin saturation is typically the first test to show abnormal results. 

For Wilson disease, there's another type of blood test called a ceruloplasmin test. Ceruloplasmin is the typically deficient liver protein that carries copper in the context of this disease. Low levels of this protein can indicate that Wilson disease is present. However, normal levels do not exclude Wilson disease, as up to 20% of patients may have normal ceruloplasmin levels. 

Further testing may be necessary, including a liver biopsy, DNA testing, or a slit-lamp eye exam to detect Kayser-Fleischer rings.

Alpha-1 antitrypsin deficiency can be tested by measuring the amounts of AAT in the blood. A low value indicates that there is a deficiency. 

For diagnosing cystic fibrosis, the most common tests include sweat test (to test the amount of chloride in sweat) and genetic testing.

Finally, a range of genetic tests can be performed to identify whether you have inherited genes associated with a disease. These tests can also specify whether you're a carrier and determine your likelihood of developing the disease. 

How are hereditary liver diseases treated? 

Genetic diseases are typically lifelong conditions, so there is no cure. However, depending on your disease and the symptoms, there are various treatments, medications, and therapies available. 

If you have a genetic liver disease, discussing your treatment options with your doctor is important. Even if you don’t need treatment immediately, it's still good to know the potential treatments you may require one day. 

The lowdown

Genetic liver diseases are linked to specific genes that are hereditary. There are numerous different types, but treatment options are available for each one. If you have any concerns about the progression of your disease or think you may need treatment, do not hesitate to ask your doctor for further advice. 

People also ask 

Which liver diseases are hereditary? 

There are numerous hereditary liver diseases. Some common examples include hemochromatosis, Wilson disease, and cystic fibrosis. 

What is the most common genetic liver disease? 

Three very common genetic liver diseases are Wilson disease, hereditary hemochromatosis, and alpha-1 antitrypsin deficiency. 

Are genetic liver diseases fatal? 

Not all genetic liver diseases are fatal. Some, like Gilbert's disease, are perfectly benign, and seeking treatment can improve your survival significantly, depending on the disease.

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