The triple A or Allgrove's syndrome (MIM*231550) is an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. Since its first description by Allgrove et al. (1978) more than 70 cases from all over the world have been reported. The syndrome manifests itself during the first decade of life with severe hypoglycaemic episodes which can cause sudden death. The frequent association with neurological disorders presenting as a mixed pattern of upper and lower motor neuropathy, sensory impairment, autonomic neuropathy and mental retardation may result in a severely disabling disease. As an additional feature some patients have hyperkeratosis of their palms and soles. We have performed a systematic genome linkage scan in eight triple A families of which three were consanguineous [including the large highly inbred kindred described by Moore et al. (1991)]. We obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, theta max = 0, Zmax = 10.81) with no indication of genetic heterogeneity. Haplotype and multipoint analyses suggest that the gene is located on a chromosomal segment flanked by the markers D12S1629 and D12S312 which are 6 cM apart. This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes.
This series describes the clinical features, aetiologies and management of juvenile Cushing's syndrome. Investigation with low and high-dose dexamethasone suppression tests and hCRH test identified the aetiology in each case. Collaboration between paediatric and adult endocrine units together with an experienced neurosurgeon and a radiotherapist contributed to the successful therapeutic outcome of these patients.
Familial glucocorticoid deficiency (FGD) is an autosomal recessive syndrome of failure of adrenal cortisol responsiveness to adrenocorticotropin (ACTH). Defects in the ACTH receptor have been suggested as a possible cause, and we have previously reported a point mutation in this gene in a family with FGD. Investigation of seven additional families has revealed a number of novel mutations in the ACTH receptor in some, but a normal gene in others suggesting that the aetiology of FGD may be heterogeneous. Using a highly polymorphic CA repeat marker (D18S40) closely linked to the ACTH receptor locus, we are now able to confirm that some cases of FGD result from defects at another locus. FGD provides an example of a single relatively homogeneous clinical syndrome resulting from two different molecular aetiologies.
Although reduced adrenocortical inner zone cell number may contribute to the lack of adrenarche, in some patients there appears to be a discrepancy between partial glucocorticoid deficiency and significantly diminished adrenal androgen secretion. These data imply a significant contribution of ACTH to the regulation of adrenarche in normal children either by having a priming effect on the adrenal gland or by acting in concert with other adrenal androgen stimulating factors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.