1/15. Missense mutations cluster within the carboxyl-terminal region of DAX-1 and impair transcriptional repression.DAX-1 is an orphan nuclear receptor that plays a key role in the development and function of the adrenal gland and hypothalamic-pituitary gonadal axis. Mutations in the gene encoding DAX-1 result in X-linked adrenal hypoplasia congenita (AHC). Affected boys typically present with primary adrenal failure in infancy or childhood and hypogonadotropic hypogonadism at the time of puberty. The majority of DAX1 mutations described to date are nonsense or frameshift mutations that result in premature truncation of the DAX-1 protein and loss of DAX-1 repressor function. Relatively few missense mutations in DAX1 have been reported. Here, we describe missense mutations in three additional families with X-linked AHC. When combined with previous reports, the DAX1 missense mutations appear to cluster within restricted regions of the putative ligand-binding domain of DAX-1 and affect amino acids that are evolutionarily conserved, suggesting that these regions correspond to critical functional domains. Transcription assays, using a variety of artificial and native target genes, were performed to assess the effects of these mutations on the function of DAX-1. All DAX-1 missense mutant constructs showed marked loss of repressor function, with the exception of I439S, a mutation previously shown to be associated with delayed-onset adrenal failure and incomplete hypogonadotropic hypogonadism. These data indicate that most DAX1 missense mutations associated with classic AHC exhibit marked loss of function. The locations of these mutations thereby identify important functional domains in the carboxyl-terminus of the protein.- - - - - - - - - - ranking = 1keywords = congenita (Clic here for more details about this article) |
2/15. Reversible secondary pseudohypoaldosteronism due to pyelonephritis.We report a 5-week-old boy who developed severe hyponatremia and hyperkalemia secondary to acute pyelonephritis. The patient presented with non-specific signs, including poor appetite, failure to thrive, and dehydration. An endocrinological evaluation led to a diagnosis of pseudohypoaldosteronism. The patient had phimosis, but no congenital urinary tract malformations. Outflow obstruction secondary to the phimosis appears to have caused pyelonephritis, and renal inflammation decreased responsiveness to aldosterone transiently.- - - - - - - - - - ranking = 1keywords = congenita (Clic here for more details about this article) |
3/15. Cardiac arrest in an infant with congenital adrenal hyperplasia.We report a 3-month-old boy who suffered an out-of-hospital cardiac arrest. During resuscitation, the medical team was informed that he was receiving hydrocortisone treatment. The possibility of adrenal insufficiency with hyperkalemic cardiac arrest prompted the administration of calcium, which resulted in the return of spontaneous circulation. The infant's diagnosis of congenital adrenal hyperplasia was not spontaneously mentioned by the parents. This case illustrates the importance of obtaining adequate parental information and considering hyperkalemia as a possible cause of cardiac arrest.- - - - - - - - - - ranking = 5keywords = congenita (Clic here for more details about this article) |
4/15. Rare causes of acute hyperkalemia in the 1st week of life. Three case reports.We describe three neonates with hyperkalemia and renal salt wasting during the 1st week of life. Endocrinological evaluation led to the diagnosis of selective hypoaldosteronism (HA) in two neonates and secondary pseudohypoaldosteronism (PHA) in one. The infant with PHA developed a urinary tract infection, and radiological investigation demonstrated a small dysplastic left kidney with vesicoureteral reflux. The electrolyte and hormonal disturbances in this infant persisted throughout the first months of life. The two infants with selective HA improved rapidly after administration of fludrocortisone orally and the electrolytes and renin values returned to normal. Secondary PHA and selective HA should be considered in the differential diagnosis in salt-losing neonates during the first days of life. Renal ultrasonography, urine culture, and assays of aldosterone and plasma renin activity should be performed in any infant presenting with hyperkalemia and salt wasting after the exclusion of congenital adrenal hyperplasia.- - - - - - - - - - ranking = 1keywords = congenita (Clic here for more details about this article) |
5/15. Complex glycerol kinase deficiency: an X-linked disorder associated with adrenal hypoplasia congenita.Complex glycerol kinase deficiency (GKD) results from the contiguous deletion on Xp21 of all or part of the gene for glycerol kinase together with that for adrenal hypoplasia congenita (AHC) and /or Duchenne muscular dystrophy (DMD). The authors present the case of a newborn whose initial issues were refractory hypoglycaemia along with hyponatremia and hyperkalemia. He also had low serum cortisol levels and raised urinary excretion of glycerol and required steroid supplementation. His creatinine phosphokinase (CPK) levels were normal. Molecular studies revealed a contiguous Xp21 deletion. Therapy in such cases must be prompt and includes correction of hypoglycaemia and dyselectrolytemia, a low fat diet and steroid replacement.- - - - - - - - - - ranking = 5keywords = congenita (Clic here for more details about this article) |
6/15. Sudden cardiac arrest in a neonate with congenital adrenal hyperplasia.We describe a 6-day-old male who developed cardiac arrest due to hyperkalemia secondary to congenital adrenal hyperplasia and was successfully resuscitated. This case illustrates the importance of considering congenital adrenal hyperplasia as one of the causes of sudden cardiac arrest in a neonate. A literature review revealed only one similar case in a 3-month-old with a fatal outcome.- - - - - - - - - - ranking = 6keywords = congenita (Clic here for more details about this article) |
7/15. Hyperkalaemic periodic paralysis and anaesthesia.Hyperkalaemic periodic paralysis is the rarer of the two forms of potassium-associated familial paralysis. We report a family with hyperkalaemic periodic paralysis with paramyotonia and the anaesthetic management of four affected members. In three of these, paralytic episodes had been precipitated by previous anaesthesia, but this was avoided in the anaesthetics described. We conclude from our experiences that with depletion of potassium before surgery, prevention of carbohydrate depletion, avoidance of potassium-releasing anaesthetic drugs and maintenance of normothermia, patients with hyperkalaemic periodic paralysis can be anaesthetised without complications. We have no evidence that they exhibit abnormal sensitivity to nondepolarising neuromuscular relaxants.- - - - - - - - - - ranking = 284.75175682566keywords = paramyotonia (Clic here for more details about this article) |
8/15. potassium uptake in muscle during paramyotonic weakness.Previous studies have suggested that an abnormal release of potassium from muscle may accompany attacks of paramyotonic weakness. We investigated 3 patients with paramyotonia congenita before and after the induction of forearm muscle weakness by exercise in cold water. Two of these patients had paralysis periodica paramyotonica and the 3rd had paramyotonia congenita. At the time of paramyotonic weakness there was a marked increase in the arterialized-venous concentration difference of potassium across forearm muscle. This indicated a significant uptake of potassium by forearm muscle in all 3 patients. Normal controls showed a slight release of potassium both at rest and after exercise in cold water. These results suggest that (1) the sodium-potassium pump of the muscle fiber is operating efficiently during paramyotonic weakness; and (2) there is a different mechanism responsible for the generalized weakness that occurs in hyperkalemic periodic paralysis.- - - - - - - - - - ranking = 2161.1252073886keywords = paramyotonia congenita, paramyotonia, congenita (Clic here for more details about this article) |
9/15. Hypokalemic paralysis in two patients with paramyotonia congenita (PC) and known hyperkalemic/exercise-induced weakness.Two male patients from a single family with known PC and "potassium sensitivity" developed hypokalemic paralysis following generalized anesthesia. These patients confirm previous similar observations. It's significance and management are discussed.- - - - - - - - - - ranking = 4322.2504147772keywords = paramyotonia congenita, paramyotonia, congenita (Clic here for more details about this article) |
10/15. Lack of cold sensitivity in hyperkalemic periodic paralysis.The nosologic distinction between paramyotonia congenita and hyperkalemic periodic paralysis is somewhat blurred. Muscle membrane inexcitability induced by cooling seems to be characteristic of paramyotonia congenita. The effect of cooling on the maximal compound muscle action potential (CMAP) in patients with paramyotonia congenita was compared to that in patients with hyperkalemic periodic paralysis. Diminution in CMAP amplitude and area, which was observed in paramyotonia congenita, did not occur in hyperkalemic periodic paralysis. We suggest that this effect of cooling on the CMAP can be utilized in the differentiation of these two syndromes.- - - - - - - - - - ranking = 4322.2504147772keywords = paramyotonia congenita, paramyotonia, congenita (Clic here for more details about this article) |
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