NeurometPlus

Incidence

Autosomal recessive. It is a rare condition. Caused by mutation in the citrin gene.

Clinical Characteristics

Citrullinemia is an autosomal recessive disease caused by a deficiency of argininosuccinate synthetase and characterized primarily by elevated serum and urine citrulline. Ohura et al. (2001) reported 3 neonates who presented with intrahepatic cholestasis associated with hypermethioninemia or hypergalactosemia detected by a neonatal mass screening. One infant was of average gestational age and had a methionine level of 134 micromol/l. His younger brother, also born at term, manifested liver dysfunction by day 3 of life. The other infant had elevated galactose levels. Plasma amino acid analysis showed significant elevation of citrulline and methionine in all 3 patients. The concentrations of threonine, tyrosine, lysine, and arginine were also 2 to 4 times higher than control levels. Organic acids in 1 patient showed elevation of hydroxyphenyllactic acid and hydroxyphenylpyruvic acid. Succinylacetone was not detected in any patients. Without specific treatment other than feeding with formula containing medium-chain triglycerides or lactose-free formula, all 3 patients had favorable clinical courses. Amino acid profiles were abnormal for the first couple of months, but resolved entirely by 12 months of age. Cholestasis improved by 3 months of age. On follow-up for 18 months to 8 years, all patients were alive and showed no developmental delay or neurologic abnormalities. Tomomasa et al. (2001) described 2 patients with type II citrullinemia who developed transient hypoproteinemia and jaundice in early infancy. Liver histology showed markedly fatty changes and fibrosis. Tazawa et al. (2001) described 3 children with neonatal-onset of type II citrullinemia who presented between 1 and 5 months of age with cholestatic jaundice. Liver histology showed fatty tissue without evidence of giant cell hepatitis, the usual finding in most forms of transient neonatal jaundice. Tamamori et al. (2002) reported 5 patients with neonatal intrahepatic cholestasis caused by citrin deficiency and confirmed by mutation analysis. Four of the patients showed a typical disease course, with spontaneous remission between 5 and 7 months of age. All patients had very high serum levels of alpha-fetoprotein.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

Urine metabolic screen. Aminoacids in plasma and urine. Apparently patients had very high serum levels of alpha-fetoprotein.