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Five children with adrenocorticotropic hormone (ACTH) insensitivity associated with autonomic nervous system disorders are described. At the time of diagnosis, four of them had osteoporosis. The fifth patient died and skeletal roentgenograms were not done. Osteoporosis was subsequently discovered in one of our previously reported patients with ACTH insensitivity. We assume that osteoporosis is, at least partly, the result of decreased adrenal androgen production. Human leucocyte antigen typing failed to establish any linkage.

A 10-year-old boy is described with a syndrome of adrenal insufficiency due to selective ACTH insensitivity associated with autonomic nervous system disorders. In addition to insufficient production of glucocorticoids and adrenal androgens, achalasia, defective lacrimation, anisocoria and hyperkeratosis of palms and soles we also found defective sweating, permanent cutis anserina and sensory polyneuropathy, which have not been reported previously in this rare syndrome.

Nonclassic steroid 21-hydroxylase deficiency is an attenuated adrenal enzyme defect that is commonly the basis of hyperandrogenic syndromes. Inherited as an autosomal recessive trait, it is known to occur with high frequency in the general population and with increased frequency in a number of ethnic groups, including the Yugoslav population. Following expansion of the original data on 21 families in Croatia to a total of 49 Croatian and Serbian families, we establish that this enzymatic disorder is increased in this Slavic population and provide an updated estimate for the gene frequency of 0.092 (0.035\x=req-\ 0.149). Also in keeping with earlier reports, we continue to note the absence of association between nonclassic 21\ x=r eq-\ hydroxylase deficiency occurring among Yugoslavs and HLA-B14;DR1.Nonclassic steroid 21-hydroxylase deficiency is an autosomal recessive disorder that is known to occur with very high frequency generally, and which in addition shows increased prevalence in certain ethnic populations (1). This partial adrenal enzyme defect may or may not be clinically manifest in af¬ fected individuals, but can be identified by hor¬ mone criteria. Mild to moderate elevations of serum androgens result from increased secretion by the adrenal of androgens and of androgenic precursors which undergo peripheral conversion to active hormones. Biochemical indices of reduced adrenal 21-hydroxylation are serum elevations of the steroid intermediates 17a-hydroxyprogesterone (17-OHP), the principal substrate of 21-hy-droxylase, which fails to be converted to 11-deoxycortisol (compound S), the direct precursor of Cor¬ tisol, and also of A4-androstenedione (A4-A), im¬ mediately distal to 17-OHP in the androgenic pathway. Clinical effects arising from 21-hydroxy¬ lase deficiency vary between individuals and the different ages within the same individual.The first population genetic study on nonclassic 21-hydroxylase deficiency (1) identified an in¬ creased incidence among Yugoslavs, estimating the gene frequency among this population to be 0.125 (0.042-0.268 (95% confidence limits)) based on data from 21 families in Zagreb, SR Croatia, Yu¬ goslavia (1). This study observed that positive link¬ age disequilibrium between nonclassic 21-hydroxy¬ lase deficiency and HLA-B14;DR1 existing in other ethnic groups at increased risk, Ashkenazic Jews, Hispanics, and Italians, was absent in the Yu¬ goslav patient group.The population genetic analysis of the original study in 167 families was based on inference of genotype and gene counting as follows: Obligate hétérozygotes (the parents of affected offspring) in each pedigree were genotyped by HLA association and ACTH stimulation hormone testing. Occur¬ rence of the nonclassic deficiency trait in a tested parent identified the presence of a nonclassic de¬ ficiency alíele also on the second haplotype. Con¬ sidering that the second (nontransmitted) haplotypes of known hétérozygotes still represent a Klinika za djecje bolesti REBRO1 and Centar za tipizaciju tkiva REBRO2,

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