METABOLIC PORTOSYSTEMIC SHUNTS“ IN ORNITHINE TRANS-CARBAMYLASE DEFICIENCY?

Abstract

Females with ornithine transcarbamylase (OTC) deficiency, an X-linked disorder, are mosaic in that they have hepatocytes with almost no enzyme activity and hepatocytes with normal enzyme activity. The normal and abnormal cells occur in clusters since cells in an area tend to be the progeny of the same parent cell. Marked variation in OTC was found in small liver biopsies from a female with OTC deficiency, probably because the samples included clusters of normal or abnormal cells. OTC activity was measured in 10 approx. 5 mg specimens of liver from a single surgical biopsy from a 7 year old girl with OTC def. (two experiments and control autopsy liver (three experiments). The OTC activity in the patient varied 10-40 fold in the two experiments with a coefficient of variation of 76 and 97 percent (control 20,21 and 26 percent). Thus OTC activity in a small biopsy in females with OTC def. may not be representative of the entire liver. The OTC activity in several bits of liver from our patient was very low suggesting that clusters of abnormal cells may often involve a major portion of a hepatic lobule. If so, blood passing through these areas would in effect be passing through a “metabolic shunt.” These shunts may, in part, account for the hyperammonemia in this disorder. The notion that an X-linked disorder can produce disease in heterozygotes by affecting small functional units could apply to other disorders such as nephrogenic diabetes insipidus or vitamin D dependent rickets.