Specific diseases Genetic		Not only have the specifics of hepatocyte uptake and excretion been worked out, as described previously, but the genetics underlying these processes have also been described in great detail. With this has come the identification of many previously unknown genetic diseases. These newly described disorders have both increased the size of the "genetic" category and decreased that of the default "idiopathic hepatitis". It is remarkable to look at the previously shown table of frequencies of various causes of neonatal cholestasis and compare it to a similar list from 1970 (below). Frequency of Causes of Neonatal Cholestasis - 1970 Idiopathic neonatal hepatitis 65% Biliary atresia 25% Endocrine/metabolic 7% Infectious/bacterial 3% (sepsis, TORCH) Frequency of Causes of Neonatal Cholestasis - 2006 Biliary atresia 25-30% Intrahepatic cholestasis 20% (Alagille, PFIC, etc) Idiopathic neonatal hepatitis 15% Alpha-1-antitrypsin deficiency 5-15% Infectious/bacterial 5-10% (sepsis, TORCH) Inborn errors of bile acid synthesis 2-5% Endocrine/metabolic 2-5% Even though any individual genetic cause of cholestasis is rare, collectively they are quite common. With this increased frequency, there has been an extra level added to the usual cholestatic workup, if the diagnosis is still in doubt. A combination of clinical features, including liver biopsy findings, serum bile acid levels and serum GGTP should allow differentiation of these various genetic disorders. For example, if the bile acids are low, disorders of bile acid synthesis are likely and urine should be tested for various metabolites to confirm this diagnosis. If the serum GGTP is low, that suggests BSEP or FIC1 deficiency, Aagenaes syndrome or ARC syndrome. The specifics of the described genetic causes of cholestasis are known. Although molecular genetic testing is not yet standardized, undoubtedly it will soon become part of the diagnostic workup. Return to top of page