Genetic analysis of carbamyl phosphate synthetase I deficiency.

Carbamyl phosphate synthetase I deficiency (CPSD) is an autosomal recessive disorder of ureagenesis characterized by hyperammonemic coma in the neonatal period. To study the genetic basis of CPSD we have performed a molecular analysis of the CPS I genes in CPSD patients from six unrelated families. Using a cDNA probe for the human CPS I gene and restriction endonuclease mapping techniques, we observed no abnormality in the number of size of the hybridizing DNA fragments from the seven affected individuals examined. These findings suggest that no gross alteration affected the CPS I genes. We did detect a frequent restriction fragment length polymorphism (RFLP) at the CPS I locus which we employed as a linkage marker. Our results suggest the polymorphic CPS I restriction fragments cosegregate with the CPSD phenotype, and that linkage disequilibrium exists between the CPSI RFLPs studied and the affected alleles. The RFLPs described may enable prenatal detection of CPSD in families where the coupling phases between CPSD alleles and RFLPs can be determined.