Immunological evidence for a carbamylphosphate synthetase lesion resulting in the formation of enzyme with altered sub-unit size.

A partial carbamylphosphate synthetase (CPS: EC 6.3.4.16) deficiency (McKusick 23730) was found in a male child who presented with generalized convulsions, rickets and apnoeic attacks at six months of age. By his second year he showed serious developmental delay and a gut biopsy revealed an absence of CPS activity with an elevated ornithine transcarbamylase activity. Analysis of the gut biopsy sample on SDS-polyacrylamide gels, followed by electrophoretic transfer to a nitrocellulose filter probed with monospecific antibodies to CPS showed that the child had normal levels of immunoreactive enzyme, but instead of one band corresponding to normal CPS with a subunit size of 165,000 u, the patient had three immunoreactive bands, one larger and two smaller than that found in normal controls. The genetic defect in this child therefore results in an unusual form of CPS being made which has markedly reduced enzyme activity.