This discussion has illustrated the enormous variety found within the category of familial
intrahepatic cholestasis. It has also demonstrated how much more there is to learn about these fascinating disorders, which may be examples of experiments in nature on bile formation. This analysis should be recognized to be the author's own, and there is much debate about this classification. For example, some workers in this field contend that North American Indian
cholestasis is in reality Byler's syndrome. Such an identity seems unlikely, given the differences between the two syndromes (Table 2). This is a field that is changing rapidly. Recently, a new cholestatic syndrome, bearing some similarities to benign recurrent
intrahepatic cholestasis, but dissimilar in several ways, has been reported. There is evidence that
cholestasis of pregnancy may be inherited as an autosomal dominant, sex-limited trait. If further studies confirm a genetic etiology, this syndrome would be the most common form of familial
intrahepatic cholestasis. The assessment of any individual case remains difficult, particularly early in the course. Table 2 can serve as a guide to the differential diagnosis of these conditions. When faced with a neonate with
jaundice, all of the usual causes must be ruled out first. The pattern of
bile acids in serum is useful for ruling out
Zellweger's syndrome. A good family history and physical examination, particularly of the heart, are important. An ophthalmologic examination by a specialist, often under
anesthesia, and a spine radiograph can be useful in confirming a diagnosis of
Alagille's syndrome. A liver biopsy, carefully interpreted with input from the clinician, is useful in pointing toward one direction or another. Often a firm conclusion cannot be reached, or is reached prematurely, so the clinician would be advised to inform the parents of all diagnostic possibilities in order to avoid false hopes or unwarranted depression. The diagnostic pitfalls to be avoided in this evaluation are many. No histologic findings are clearly pathognomonic for one syndrome or another. Giant cell transformation and paucity of intrahepatic bile ducts may be found in several syndromes.
Biliary atresia, or at least failure to demonstrate a patent biliary tree from the liver to the cystic duct, may be present in patients with
Alagille's syndrome. In that syndrome, the eye findings, particularly the posterior embryotoxon, may not be appreciated except on extensive ophthalmologic testing, including gonioscopy. Butterfly vertebrae may not be visible at birth and may be no longer evident in adulthood.(ABSTRACT TRUNCATED AT 400 WORDS)