INBORN-ERRORS OF STEROID-BIOSYNTHESIS

The aberrations in steroidogenesis are thought to evolve either from the reduced ability to produce an enzyme catalyzing a particular biosynthetic step or from the production of an aberrant enzyme that, because of its altered substrate specificity, channels steroid intermediates into an unusual metabolic pathway. For each syndrome there is at least presumptive evidence that the respective defects arise from information that is genetically transmitted. However, whereas a quantitative alteration indicates a modification in a regulatory gene resulting in the decreased production of a given enzyme, a qualitative alteration must derive from a mutation in a structural gene, thereby giving rise to the production of an enzyme with altered catalytic properties. The development of an alternate means of assessing the presence of a particular enzyme or its constituent components might enable one to determine which of the above mechanisms is operative in the respective syndromes. At present no unequivocal answer can be offered to favor one of the alternatives; the possibility remains that each of them may be operative in different cases and give rise to conditions with undifferentiable pathology but different etiology. On a more practical level, there is the need to develop and implement procedures for identifying heterozygous carriers of the affected genes, particularly for the two most common forms of CAH that account for 85-95% of all the cases seen clinically. It is possible to identify individuals who are heterozygous for the 21-hydroxylation deficiency by their excretion of pregnanetriolone after ACTH stimulation; this suggests that combined studies of steroid-excretion patterns and genetic screening might be of significant value in determining heterozygous individuals in the other variants of CAH.