A Report of Four Cases, Including Three in One Sibship, With Comparative Histologic Evaluation of the Juxtaglomerular Apparatuses and Glomeruli

Abstract

Summary and Conclusions An electrolyte‐losing syndrome is described in three siblings, including one set of twins, and in an unrelated infant who was the product of incest. In most respects the clinical and laboratory findings in these patients were compatible with the condition which has come to be known as Bartter's syndrome. In all four of our patients, however, symptoms were manifested early in life, the disease ran a malignant course and death occurred early. Electron microscopic examination of the kidneys from two of our patients showed characteristic structural changes in the glomeruli including immaturity of the podocytes and extensive loss or fusion of their foot processes. Light microscopy of the kidneys from all four cases showed an unusually large proportion of immature glomeruli that seemed to diminish slowly with age. Some ninety per cent of these small glomeruli were located peripherally. The incidence and size of hypertrophied JGA, also the degree and extent of hyperplastic arterial thickening, appeared to increase with age. These findings are discussed in relation to the hypothesis that the basic abnormality in Bartter's syndrome may involve a defect of sodium reabsorption in the proximal tubule, and that this leads to hypertrophy of the JGAs of functioning nephrons with excessive production and release of renin, which causes vasoconstrictive dormancy of the more peripheral glomeruli.

Bartter’s Syndrome

“…Indeed, it has been shown that abnormal glucose tolerance tests are present in some patients with Bartter's syndrome [78]. increased plasma growth hormone and hypoglycemic unresponsiveness have been demonstrated during standard insulin tolerance tests [74] The possibility also exists between the generally poor nutritional status and the carbohydrate metabolic dis order.…”

“…87] although no inherited case is known. In 2 case reports involving consanguineous relations, autosomal recessive pattern of transmission is suggested [5,78], Symptoms and signs of hypokalemia (muscular weak ness, polyuria) associated with enuresis and vomiting may develop abruptly, last for a few days and be resolved spon taneously with rest. Despite the severe hypokalemia, pa ralysis is extremely rare although recurrent tetany has been described.…”

Altered membrane sodium transport in Bartter's syndrome

“…Bartter's syndrome has been presumed to be a genetic disorder with an autosomal recessive pattern of inheritance (2) and has been reported to occur among siblings (4)(5)(6) and in one patient who was the product of a consanguineous union (6). To explore the possibility that Bartter's syndrome is a manifestation of a generalized, inherited abnormality of sodium transport, we have measured various parameters of sodium transport in erythrocytes from patients with Bartter's syndrome, their siblings and their parents.…”

Growth Failure in Children with Metabolic Alkalosis and with Metabolic Acidosis

“…It is well known that potassium deficiency leads to loss of carbo hydrate tolerance [13]. Indeed, it has been shown that abnormal glucose tolerance tests are present in some patients with the syndrome [14]. Hypoglycemic unrespon siveness and increased plasma growth hormone have been demonstrated during standard insulin tolerance tests [15].…”