CTLN2 differs from classical citrullinaemia (CTLN1, OMIM 215700) in that CTLN1 is neonatal or infantile in onset, with ASS enzyme defects (in all tissues) arising due to mutations in ASS on chromosome 9q34 (refs 18-21).
Adult-onset type II citrullinemia (CTLN2) is a form of the disease that is defined by a quantitative decrease in ASS protein, but with normal kinetic properties.
The gene causing CTLN2 (SLC25A13) was identified by positional cloning (from 7q21.3) and found to encode a putative calcium-dependent mitochondrial carrier protein.
Adult-onset type II citrullinemia (CTLN2) is characterized by a liver-specific argininosuccinate synthetase deficiency caused by a deficiency of the citrin protein encoded by the SLC25A13 gene.
These results demonstrate that citrin and aralar1 are isoforms of the hitherto unidentified aspartate/glutamate carrier and explain why mutations in citrin cause type II citrullinemia in humans.
Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: Identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations.
Type II citrullinaemia (CTLN2) is an adult- or late childhood-onset liver disease characterized by a liver-specific defect in argininosuccinate synthetase protein.
These methods have shown that more than 90% of the patients diagnosed as suffering from CTLN2 by enzymatic analysis carry SLC25A13 mutations in both alleles, indicating that CTLN2 is caused by citrin deficiency.
By using homozygosity mapping and positional cloning, we have shown that adult-onset type II citrullinemia (CTLN2) is caused by mutations of the SLC25A13 gene, which is localized on chromosome 7q21.3 and encodes a mitochondrial solute carrier protein named citrin.
Adult-onset type II citrullinemia (CTLN2), characterized by a liver-specific deficiency of urea cycle enzyme, argininosuccinate synthetase, is caused by mutations in SLC25A13 that encodes a calcium binding mitochondrial solute carrier protein, citrin.