Arteriohepatic dysplasia is a genetic disorder that mimics other forms of prolonged liver disease in infants and young children. However, a group of unusual features in other organ systems distinguishes Arteriohepatic dysplasia from other liver and bile duct diseases in infants. It is also known as Allagile syndrome. The gene for this disorder has been discovered on chromosome 20 in band 20p12.
Children with arteriohepatic dysplasia usually have a liver disease characterized by a progressive loss of the bile ducts within the liver over the first year of life and narrowing of the bile ducts outside the liver. This leads to a buildup of bile in the liver, causing damage to liver cells. Scarring may occur and lead to cirrhosis in about 30 to 50 percent of affected children. Arteriohepatic dysplasia was first described in 1969 by D. Alagille, in French medical literature.
Arteriohepatic dysplasia is generally inherited from one parent and there is a 50 percent chance that each child will develop the syndrome. Each affected adult or child may have all or only a few of the features of the syndrome.
Frequently, a parent or brother or sister of the affected child will share the facial appearance, heart murmur or butterfly vertebrae, but have a completely normal liver and bile ducts.
Symptoms of the illness are jaundice (yellowing of skin and eyes), pale, loose stools and poor growth within the first three months of life. Later there is persistent jaundice, itching, fatty deposits in the skin, and stunted growth and development during early childhood.
Frequently, the disease stabilizes between ages 4 and 10 with an improvement in symptoms.
Other features that help establish the diagnosis include abnormalities in the cardiovascular system, the spinal column, the eye, and the kidneys. Narrowing of the blood vessels connecting the heart to the lungs (pulmonary artery) leads to extra heart sounds but rarely problems in heart function.
The shape of the bones of the spinal column may look like the wings of a butterfly on x-ray but almost never cause any problems with function of the nerves in the spinal cord.
Many physicians believe that there is a specific facial appearance shared by many of the children with arteriohepatic dysplasia. The features include a prominent, broad forehead, deep-set, widely spaced eyes, broad forehead, malformed or low-set ears, a long, straight nose and a small pointed chin.
More than 90 percent of children with arteriohepatic dysplasia have an unusual abnormality of the eyes. An extra, circular line on the surface of the eye requires specialized eye examination to detect and does not lead to any disturbances in vision. Patients may also develop kidney problems (nephropathy).
Vitamin A deficiency causes night blindness and red eyes. Vitamin D deficiency causes softening and fractures of the bones and teeth (rickets). Vitamin E deficiency causes a disabling disease of the nervous system and muscles, and vitamin K deficiency causes bleeding problems.
Treatment is primarily medical and not surgical. Patients generally have a much better outcome than children with some other liver diseases that may present at the same age.
Treatment of arteriohepatic dysplasia is based on increasing the flow of bile from the liver, maintaining normal growth and development, and preventing or correcting any of the specific nutritional deficiencies that often develop. Because bile flow from the liver to the intestine is slow in arteriohepatic dysplasia, medications designed to increase the flow of bile are frequently prescribed. This may decrease the damage in the liver and improve the digestion of fat in foods that are eaten.
Also, itching caused by the buildup of bile in the blood and skin may be relieved by medications including diphenhydramine (Benadryl) and hydroxyzine hydrochloride (Atarax). Elevations in blood cholesterol also respond to the medications used to increase bile flow. Lowering blood cholesterol usually causes the cholesterol skin deposits to improve.
Although reduced flow of bile into the intestine leads to poor digestion of dietary fat, a specific type of fat can still be well digested and therefore infant formulas containing high levels of medium-chain triglycerides - MCT - are usually substituted. Deficiencies of the vitamins A, D, E, and K can usually be corrected by oral doses.
Sometimes, surgery is necessary during infancy to help establish the diagnosis of arteriohepatic dysplasia by direct examination of the bile duct system. However, surgical reconstruction of the bile duct system is often not recommended. Occasionally, liver cirrhosis advances to a stage where the liver fails to perform its functions. Liver transplantation is then considered.