ABSTRACT
The activities of the carboxylases may be measured in leukocyte extracts or in fibroblasts, as well as in tissues. The gene for holocarboxylase synthetase has been cloned and assigned to chromosome 21q22. The initial impression that the forms of multiple carboxylase deficiency could be differentiated by the age of onset has not held up, although those with holocarboxylase synthetase abnormalities have generally presented within the first six weeks of life, while those with biotinidase deficiency have generally presented after six months of age. The levels of activity of the enzymes are dependent on the concentrations of biotin in the medium. The covalent binding to biotin conveys enzymatic activity and holocarboxylase status to the apocarboxylase protein, which is inactive prior to this conversion. Prenatal diagnosis has been accomplished by the demonstration of biotin-responsive deficiencies of carboxylases in cultured amniocytes.
