Hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness.
OBJECTIVE
To characterize a rare inherited hypokalemic salt-losing tubulopathy with linkage to chromosome 1p31.


METHODS
We conducted a retrospective analysis of the clinical data for 7 patients in whom cosegregation of the disease with chromosome 1p31 had been demonstrated. In addition, in 1 kindred, prenatal diagnosis in the second child was established, allowing a prospective clinical evaluation.


RESULTS
Clinical presentation of the patients was homogeneous and included premature birth attributable to polyhydramnios, severe renal salt loss, normotensive hyperreninemia, hypokalemic alkalosis, and excessive hyperprostaglandin E-uria, which suggested the diagnosis of hyperprostaglandin E syndrome/antenatal Bartter syndrome. However, the response to indomethacin was only poor, accounting for a more severe variant of the disease. The patients invariably developed chronic renal failure. The majority had extreme growth retardation, and motor development was markedly delayed. In addition, all patients turned out to be deaf.


CONCLUSIONS
The hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness represents not only genetically but also clinically a disease entity distinct from hyperprostaglandin E syndrome/antenatal Bartter syndrome. A pleiotropic effect of a single gene defect is most likely causative for syndromic hearing loss.
Jeck
N
N
Departments of Pediatrics, Marburg, Germany.
Reinalter
S C
SC
Henne
T
T
Marg
W
W
Mallmann
R
R
Pasel
K
K
Vollmer
M
M
Klaus
G
G
Leonhardt
A
A
Seyberth
H W
HW
Konrad
M
M
D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001477:Bartter Syndrome / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003241:Consanguinity; D003404:Creatinine / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D003638:Deafness / Q000235:genetics*; D015232:Dinoprostone / Q000378:metabolism* / Q000652:urine; D004231:Diuresis; D005260:Female; D008040:Genetic Linkage; D006130:Growth Disorders / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007008:Hypokalemia / Q000188:drug therapy / Q000235:genetics*; D007213:Indomethacin / Q000627:therapeutic use; D007223:Infant; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology / Q000648:ultrastructure; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D007861:Lebanon; D008297:Male; D010375:Pedigree; D010641:Phenotype; D015499:Renal Tubular Transport, Inborn Errors / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D013577:Syndrome; D016896:Treatment Outcome; D014421:Turkey; D014463:Ultrasonography
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D003404:Creatinine; D015232:Dinoprostone; D007213:Indomethacin