A Genetic Study of Neonatal Obstructive Jaundice

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Abstract
The diagnostic criteria are presented on which 110 cases of neonatal obstructive jaundice seen over 16 years were classifed as extrahepatic biliary atresia (58 cases), intrahepatic biliary atresia (seven cases) or "neonatal hepatitis" (50 cases including five additional cases without jaundice in the newborn period). The natural history of these diseases is described, and it is concluded that only one-third to one-half of cases of "neonatal hepatitis" recover fully. Familial, clinical and pathological data on those cases whose parents could be traced (47, seven and 45 cases respectively) are presented. There is adequate evidence to show the absence of a familial tendency, of influence of maternal age or of birth order, or of any disturbance of fetal growth in extrahepatic biliary atresia. In intrahepatic biliary atresia 13 cases (these seven with six from the literature) have no affected relatives. The finding of four consanguineous unions among the parents of the cases of "neonatal hepatitis" is the basis for suggesting a mutant autosomal gene in homozygous form as the cause of the disease. Even after stringent searching through index cases to exclude those that might have another cause, only 12 of 71 siblings of index cases were also affected (p = 0.169 [plus or minus] 0.044). Some infants with the genotype for the disease manifest it so mildly or perhaps so severely that the diagnosis is not made. The apparent excess of male over female index cases may be other evidence of failure of manifestation of the genotype. Alternatively these cases may still be of more than one disease. A marked decrease in birth weight is demonstrated in "neonatal hepatitis", and seems important confirmation of profound disturbance of liver function in the fetus. The abnormal genotype may determine a deficiency of an enzymatic activity needed by the fetus, but not the infant.