Alagille syndrome.

Alagille syndrome is an inherited disorder that mimics other forms of prolonged liver disease seen in infants and young children. However, a group of unusual features in other organ systems distinguishes Alagille syndrome from other liver and bile duct diseases in infants.

Children with Alagille syndrome 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 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 per cent of affected children.

Symptoms of the illness are jaundice, pale, loose stools and poor growth within the first three months of life. Later there is persistent jaundice, itch ing, 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 which help establish the diagnosis include abnormalities in the cardiovascular system, the spianal column, the eye and the kidneys. Narrowi ng of the blood vessel connecting the heart to the lungs (pulmonary artery) leads t o extra heart sounds but rarely problems in heart functions. 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 functions of the nerves in the spinal cord.

More than 90 per cent of children with Alagille syndrome have an unusual abnormality of the eyes. An extra, circular line on the surface of the eye requ ires specialized eye examination to detect and does not lead to any disturbances in vision. In addition, some children have various abnormalities in their kidneys that may lead to minor changes in kidney function.

Many physicians believe that there is a specific facial appearance shared by most of the children with Algille syndrome that makes them easily recognizable. The features include a prominent, broad forehead, deep-set eyes, a straight nose and a small pointed chin.

Alagille syndrome is generally inherited only from one parent and there is a 50 per cent chance that each child will develop the syndrome. Each affected a dult 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, hear murmur or butterfly vertebrae, but have a completely normal liver and bile ducts.

Treatment of Alagille syndrome is based on trying to increase the flow of bile from the liver, maintain normal growth and development and prevent or corre ct any of the specific nutritional deficiencies that often develop. Because bile flow from the liver to the intestine is slow in Alagille syndrome, medications designed to increase the flow of bile are frequently prescribed, including phenorbarbital and Questran or colistipol. This may decrease the damage in the liver and improve the digestion of fat in foods that are eaten.

Also, itching caused by the bulidup of bile in the blood and skin may be relieved. Other drugs are also used to relieve itching (Benadryl, Atarax). Ele vations in blood cholesterol also respond to the medications used to increase bile flow. Elevated blood cholesterol levels can lead to small yellow deposits of cholesterol on the skin of knees, elbows, palms, eyelids and other surfaces that are frequently rubbed. Lowering blood cholesterol usually causes the cholesterol skin deposits to improve. Although these are unsightly, they are almost never associated with any dangerous symptoms.

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 -- a re usually substituted for conventional formulas. Trade names are Pregestamil and Portagen. Some infants can grow adequately on breast milk if additional MCT oil is given. Foods containing fat may lead to looser, greasy stools later in childhood. However, the benefits from the calories and vitamins in the fat that is absorbed usually leads to the recommendation that the child not be put on a low-fat diet. There are no other dietary restrictions. Occasionally, MCT oil is also prescribed as a nutritional supplement.

Problems with fat digestion and absorption may lead to deficiency of fat-soluble vitamins -- A,D,E and K. Vitamin A deficiency causes night blindnes s 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 muscle, and vitamin K deficiency causes bleeding problems. Deficiencies of these vitamins can be diagnosed by blood tests and us ually can be corrected by large oral doses. If the child's system cannot absorb vitamins given by mouth, vitamin injections into the muscle are necessary.

Sometimes surgery is necessary during infancy to help establish the diagnosis of Alagille syndrome by direct examination of the bile duct system. However, surgical reconstruction of the bile duct system is not recommended because bile can still flow from the liver and there is presently no procedure that can correct for the loss of the bile ducts within the liver. Occasionally liver cirrhosis advances to a stage where the liver fails to perform its functions. Liver transplantation is then considered.

The overall life expectancy for children with Alagille syndrome is unknown, but depends on several factors: the severity of scarring in the liver, whether heart or lung problems develop because of the narrowing in the pulmonary artery, and the presence of infections or other problems related to poor nutrition. Many adults with Alagille syndrome are leading normal lives.

Although Alagille syndrome was first described in the English medical literature in 1975, it is now becoming recognized more frequently among children with chronic forms of liver disease. Diagnosis can be established by microscopic examination of liver biopsy specimens, a stethoscope examination of the child's heart and chest, a special eye examiantion (slit-lamp exam), an x-ray of the spinal column and an ultrasound (sonogram) examination of the abdomen.

Treatment is primarily medical and not surgical. Patients generally have a much better outcome than children with some of the other liver diseases that may present at the same age.