Intrahepatic Cholestasis Secondary to Citrin Deficiency

Citrin deficiency (neonatal-onset type II citrullinemia), is an autosomal recessive metabolic disorder, caused by a mutation of the SLC25A13 gene. The defective transport between the mitochondria and the cytosol, leads to insufficient substrate for argininosuccinate synthetase (ASS) and secondary functional deficiency of ASS activity [1]. Infants with citrin deficiency, have transient intrahepatic cholestasis, hepatic steatosis and parenchymal cellular infiltration associated with hepatic fibrosis, low birth weight, and growth retardation. Citrin deficiency as a cause of neonatal intrahepatic cholestasis occurs almost exclusively in Asian infants. The incidence is 1/19000 in Japan, 1/50000 in Korea and 1/17000 in China. The frequency of SLC25A13 homozygotes in China, were calculated to be 1/9200 to the south of the Yangtze river and 1/3500000 to the north of the Yangtze river [2]. Later in life, some of these patients may develop adultonset citrullinemia type II which is characterized by fatty liver, hyperammonemia, and neurological symptoms, with sudden onset of disorientation, abnormal behavior, convulsions and coma due to hyperammonemia [3]. Plasma amino acids analysis showed significant elevation of citrulline, methionine and threonine. Abstract