Hereditary recurrent intrahepatic cholestasis from birth

Abstract

Sixteen cases of neonatal cholestasis, all related, with consanguinity in 6 of 7 parental couples are reported. The children had an obstructive type of jaundice from the first week of life. The jaundice lasted from about 1 to 6 years, and in this period the patients complained of severe itching. Other symptoms, such as bleeding tendency, rickets, anaemia, and growth retardation were ascribed to malabsorption. Seven children died in infancy, at least 5 as a result of haemorrhages, but no death from haemorrhage has occurred since vitamin K has been regularly used. Laboratory examinations showed hyperbili-rubinaemia (conjugated bilirubin), increased transaminases and alkaline phosphatases, hyper-lipaemia, and increase in pre-β and β-lipoproteins, slight decrease in albumin, and increase in α2-globulin. After the end of the cholestatic period, the children started to regain normal stature, and adult height was normal. From prepuberty patients tended to develop oedema of the legs, for no known reason. One or more further periods of cholestasis have recurred in all adult patients. Liver histology showed 'giant cell hepatitis', but this did not progress to fibrosis. The parents showed a slight but significant increase in serum bilirubin, possible evidence of heterozygosity. The term 'hereditary, recurrent, intrahepatic cholestasis from birth' is proposed for this new inborn error of metabolism.