The genetic disorder results in a deficiency in argininosuccinate synthetase, leading to enzymatic disruption of the urea cycle. The mutation involves a single-base substitution (C-T) in exon 5 of argininosuccinate synthetase (ASS), which converts the CGA codon that codes for arginine-86 to TGA, a translational termination codon. This results in a truncated peptide product (85 amino acids instead of 412) deprived of functional activity.
Clinically, citrullinemia causes ammonemia (increased circulatory ammonia) and associated neurological signs. Affected calves present with ataxia, aimless wandering, blindness, head pressing, convulsions and death.
Diagnosis is based on PCR analysis (polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)) of suspect cases and for screening of potential sires.
Treatment is usually unsuccessful and most affected animals are euthanized. Recent gene therapy, using viral vectors to express human argininosuccinate synthetase resulted in calves showing clinical improvement and normalization of plasma glutamine levels after treatment.
As artificial insemination is widely used in dairy cattle breeding, carriers of citrullinemia are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population.
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