Causing chronic liver injury/failure
Alpha-1-antitrypsin deficiency: Alpha-1 antitrypsin deficiency (sometimes just called “Alpha-1”) is an inherited genetic disorder that causes low levels of a protein (AAT) that protects your lungs. Alpha-1 increases your risk of developing certain diseases, including emphysema (damaged air sacs in your lungs), cirrhosis (liver scarring) and panniculitis (an uncommon skin condition). Some of these conditions can be life-threatening. Alpha-1 antitrypsin deficiency affects people who have two copies of the SERPINA1 gene that makes an abnormal type of the Alpha-1 protein. These gene changes can cause your body to have low levels of AAT or no AAT in your lungs, and, depending on the changes, a buildup of AAT in your liver. If a gene mutation causes low levels of AAT or creates incorrectly formed AAT, you won’t have enough in your lungs to stop elastase, which will start breaking down the protein elastin in your lungs. Elastin gives strength to the small air sacs of your lungs (alveoli) and allows them to stretch and contract, like a rubber band. Without it, your alveoli lose their shape and become floppy. This makes it so you can’t breathe or get oxygen properly. This is a condition called emphysema.
Progressive familial intrahepatic cholestasis
Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete bile, and the buildup of bile in liver cells causes liver disease. There are three known types of PFIC: PFIC1, PFIC2 and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause. PFIC symptoms typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension) and an enlarged liver and spleen (hepatosplenomegaly). In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis) and low levels of fat-soluble vitamins (vitamins A, D, E and K) in the blood. Affected individuals typically develop liver failure before adulthood. The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma. Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3.
Allagille syndrome
Alagille syndrome is a genetic disorder that can affect the liver, heart, and other parts of the body. One of the major features of Alagille syndrome is liver damage caused by abnormalities in the bile ducts. These ducts carry bile (which helps to digest fats) from the liver to the gallbladder and small intestine. In Alagille syndrome, the bile ducts may be narrow, malformed, and reduced in number (bile duct paucity). As a result, bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream. Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itchy skin, and deposits of cholesterol in the skin (xanthomas).
Cystic fibrosis liver disease
Cystic fibrosis (CF) is an autosomal recessive disorder that commonly affects the White population, with an annual incidence of approximately 1 in 3,500 live births. This multisystem disorder is characterized by genetic mutations in the CF transmembrane conductance regulator (CFTR) gene on chromosome 7, which encrypts a protein essential for regulating transmembrane chloride reabsorption. CFTR, a chloride channel, is expressed in secretory epithelial cells lining the airways, digestive system, reproductive system, and skin. Homozygous mutations in the CFTR gene impair the transport of chloride ions and the movement of water into and out of cells, resulting in the inspissation of secretions and leading to organ dysfunction. Although CF commonly affects the airways, approximately 10% to 15% of patients with CF demonstrate cystic fibrosis-associated liver disease (CFLD). The improvement in the diagnostic modalities and management of CF has positively impacted the life expectancy of patients with CF. Consequently, there has been a significant emergence of liver dysfunction in CF, complicating the clinical course of the disease. CFTR dysfunction has a significant effect on cholangiocyte function causing an alteration in the final bile composition that causes chronic damage to the biliary epithelium, resulting in the development of a broad spectrum of hepatobiliary complications ranging from cholestasis, progressive periportal fibrosis, biliary obstruction causing focal biliary cirrhosis which may progress to multinodular cirrhosis, portal hypertension, and hepatic decompensation.
Tyrosinemia
Tyrosinemia is a genetic disorder characterized by problems breaking down the amino acid tyrosine, which is a building block of most proteins. If the condition is untreated, tyrosine and its byproducts build up in tissues and organs, which can lead to serious health problems. There are three types of tyrosinemia, distinguished by their symptoms and genetic cause. Tyrosinemia type I is the most severe form of this disorder and usually begins in the first few months of life. Affected infants do not gain weight and grow at the expected rate (failure to thrive) because eating high-protein foods leads to diarrhea and vomiting. Affected infants may also have yellowing of the skin and whites of the eyes (jaundice), a cabbage-like odor, and an increased tendency to bleed (particularly nosebleeds).