Bartter and related syndromes: the puzzle is almost solved

Abstract

It is now evident that the term Bartter syndrome does not represent a unique entity but encompasses a variety of disorders of renal electrolyte transport. Application of molecular biology techniques has permitted a better understanding of these "Bartter-like syndromes," which at present can be divided into three different genetic and clinical entities. Neonatal Bartter syndrome is observed in newborn infants and characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Two molecular defects have been identified: either at the gene encoding the renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the gene encoding an ATP-sensitive inwardly rectifying K channel (ROMK). "Classic" Bartter syndrome is mostly observed during infancy and childhood and is characterized clinically by polyuria and growth retardation. Nephrocalcinosis is not present. Very recently, either deletions or mutations at the gene encoding a renal chloride channel (ClC-Kb) have been identified. Gitelman syndrome is observed in older children and adults presenting with intermittent episodes of muscle weakness and tetany, hypokalemia, and hypomagnesemia. Mutations at the gene encoding the thiazide-sensitive Na-Cl cotransporter have been identified in the majority of patients studied. Obviously the validity of this classification must be confirmed in the near future when all mutations have been described and genotypic-phenotypic correlations are better defined.

Clinical and Genetic Spectrum of Bartter Syndrome Type 3

“…As 20 expected, gestational age (GA) at birth was significantly lower in the A/NBS group than in 21 the CBS and GLS groups, but similar between the CBS and GLS groups. Age at diagnosis 22 was significantly lower in the A/NBS group than in the other two groups and in the CBS 23 group than in the GLS group. Polyhydramnios was found in 29 patients with A/NBS (85%), 24 at mean GA of 28 weeks, and amniotic fluid had to be drained in four cases.…”

“…31 Centre Hospitalier Pierre Oudot de Bourgoin-Jallieu, Service 23 de Pédiatrie, Bourgoin-Jallieu, France. 32 Methods: Genetic analyses were performed by direct sequencing and multiplex ligation-7 dependent probe amplification; medical charts were analyzed retrospectively for 115 patients 8 with CLCNKB mutations.…”

“…GS is related to 21 loss-of-function mutations of the SLC12A3 gene encoding the apically expressed thiazide-22 sensitive NaCl cotransporter (NCC) of the distal convoluted tubule (DCT) 12 . 23 The first BS3 patients described had a clinical phenotype corresponding to CBS 7 . 24 Considerable phenotypic variability has since been described: CLCNKB mutations can also 25 6 underlie the ABS, neonatal BS (NBS), and Gitelman-like (GLS) phenotypes [13][14][15] families.…”

“…One of 18 the main criteria of a successful treatment is a normal growth; in this cohort, 63 out 77 19 patients (82%) had a height between -2 SD and +1 SD or a normal height as adults. Fourteen 20 patients had height below -2SD: five A/NBS patients including one with GH deficiency (IGF1 21 = 38 ng/ml before GH initiation at 15 years of age), eight CBS patients including two with 22 GH deficiency and two with chronic kidney disease (CKD), and one GLS patient with no 23 identified cause of failure-to-thrive. 24 Abnormalities in psychomotor and neurological development included psychomotor 1 retardation in four A/NBS and four CBS patients (Table 3).…”

Endocrinology: Hyperaldosteronism in a cat with metastasised adrenocortical tumour

“…In the former group volume expansion leads to suppressed renal renin secretion and hypertension, whereas in the latter group volume depletion stimulates renin secretion. In humans, the second group comprises a number of genetic disorders in children and young adults, known as syndromes of Bartter and Gitelman, which are the result of inborn defects in renal electrolyte transport (26). The hypokalaemia and episodic weakness with neck ventroflexion known to occur in young Burmese cats (16) .…”