Bacterial expression of mutant argininosuccinate lyase reveals imperfect correlation of in-vitro enzyme activity with clinical phenotype in argininosuccinic aciduria.

Background: The urea cycle defect argininosuccinate lyase (ASL) deficiency has a large spectrum of presentations from highly severe to asymptomatic. Enzyme activity assays in red blood cells or fibroblasts, although diagnostic of the deficiency, fail to discriminate between severe, mild or asymptomatic cases. Mutation/phenotype correlation studies are needed to characterize the effects of individual mutations on the activity of the enzyme.

TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations.

Transcobalamin II (TC II) is a plasma transport protein for cobalamin. TC II deficiency can lead to infant megaloblastic anemia, failure to thrive and to neurological complications. This report describes the genetic work-up of three patients who presented in early infancy.

Investigation of citrullinemia type I variants by in vitro expression studies.

Mild citrullinemia is an allelic variant of classical citrullinemia type I also caused by deficiency of the urea cycle enzyme argininosuccinate synthetase (ASS). Affected patients comprise a biochemical but no clinical phenotype. However, there is no reliable parameter allowing conclusions regarding the course of the disorder or its type of manifestation.

Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia.

Background: In the course of 25 years, we have experienced a high rate of affected fetuses in the prenatal diagnosis of citrullinemia.

Methods And Results: Ninety-one pregnancies at 1 in 4 risk were tested; 36 were diagnosed as affected (39.5%; P = 0.

Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1).

Citrullinemia is caused by either deficiency of argininosuccinate synthetase (ASS, citrullinemia type 1) or a defect of the SLC25A13 gene encoding a mitochondrial aspartate-glutamate transporter (citrullinemia type II). Citrullinemia type 1-referred to as classical citrullinemia-is characterized by largely elevated concentrations of citrulline, manifesting with acute hyperammonemic crises predominantly early in life and occurs panethnically. Citrullinemia type II is a rare multisystem-disorder nearly exclusively observed in the Japanese population and characterized by less pronounced elevations of plasma citrulline and mainly a late onset of clinical symptoms.