Congenital Adrenal Hypoplasia in Siblings

Mitchell, Robert J.; Rhaney, K.

doi:10.1016/s0140-6736(59)91020-7

Cited by 49 publications

(16 citation statements)

References 19 publications

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“…In other reports concerning adrenal hypoplasia in siblings (6,(9)(10)(11), it is difficult to establish a common lesion in each family, since in no studies are pathological observations correlated with precise biochemical data. Steroids are still measured by methods developed for the analysis of body fluids from adults despite reports of the vast differences in the nature of the hormones secreted by the adrenals of the neonates (12).…”

Section: Discussionmentioning

confidence: 96%

Deficient 3β-Hydroxy-5-Ene Steroid Secretion by Newborn Infants

Shackleton

Swift

Savage

et al. 1979

The Journal of Clinical Endocrinology & Metabolism

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Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone.

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Section: Discussionmentioning

confidence: 96%

Deficient 3β-Hydroxy-5-Ene Steroid Secretion by Newborn Infants

Shackleton

Swift

Savage

et al. 1979

The Journal of Clinical Endocrinology & Metabolism

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“…Mutations in DAX-1 have been shown to be responsible for X-linked congenital adrenal hypoplasia (AHC), a rare disorder characterized by impaired development of the adrenal cortex and hypogonadotropic hypogonadism (1,2). AHC was first described by Sikl et al (3) and was suggested to be familial after its description in a male sibship (4). Males with DAX-1 mutations generally present with adrenal failure early in life and hypogonadotropic hypogonadism in adolescence, although milder forms of the syndrome have been described (5).…”

mentioning

confidence: 99%

Identification of a Novel Missense Mutation That Is as Damaging to DAX-1 Repressor Function as a Nonsense Mutation

Brown

Scobie

Townsend

et al. 2003

The Journal of Clinical Endocrinology & Metabolism

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Mutations in the DAX-1 (NROB1) gene result in X-linked congenital adrenal hypoplasia (AHC) and hypogonadotropic hypogonadism. The clinical presentation is usually as adrenal insufficiency in early life, with hypogonadotropic hypogonadism detected at the time of expected puberty. In this study we identified mutations in the DAX-1 gene of two patients with AHC. One mutation, Y399X, resulted in a premature stop codon and was associated with loss of Leydig cell responsiveness to human chorionic gonadotropin. The second, L297P, was a missense mutation, and human chorionic gonadotropin responsiveness was maintained. Kindred analysis established that the mutations had been inherited from the proband's mothers. The L297P has not been described previously and occurs within a highly conserved binding motif (LLXLXL). Transient transfection assays demonstrated that both mutations resulted in a severe loss of DAX-1 repressor activity. Immunohistochemical analysis of testicular tissue obtained from an affected sibling of the subject with the Y399X mutation, who had died with adrenal failure as a neonate, showed normal testicular morphology and expression of DAX-1, steroidogenic factor-1, and anti-Mullerian hormone protein. These data extend the clinical and molecular information on DAX-1 mutations, confirm normal testicular development at the neonatal stage, and illustrate variability in Leydig cell function.

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“…Mitchell and Rhaney (1959) reported it in two brothers, the first dying at 53 days and showing hypoplasia of the adrenal glands as the only apparent cause of death. The brother was born three years later, and exhibited a similar clinical picture of vomiting, wasting and dehydration shortly after birth.…”

mentioning

confidence: 99%