Problems in diagnosing atypical Gitelman's syndrome presenting with normomagnesaemia.
OBJECTIVE
Gitelman's syndrome, recognized as a variant of Bartter's syndrome, is characterized by hypokalaemic metabolic alkalosis in combination with hypomagnesaemia and hypocalciuria. Overlapping biochemical features in Gitelman's syndrome and Bartter's syndrome has been observed. Here, we investigated the clinical, biochemical, and genetic characteristics of five, chronic, nonhypertensive and hypokalaemic Japanese patients.


METHODS
Serum and urinary electrolytes, plasma renin activity and plasma aldosterone concentration were measured in five patients (four males and one female) with hypokalaemia. Renal clearance tests were performed and distal fractional chloride reabsorption calculated. Finally, mutational analysis of the thiazide-sensitive Na-Cl co-transporter gene was performed.


RESULTS
Symptoms in patients varied from mild (muscle weakness and numbness) to severe (tetany and foot paralysis). All patients were normotensive or hypotensive, and all had hypokalaemia, hypocalciuria, and hyperreninaemic hyperaldosteronism. However, two male patients had normomagnesaemia, while the remainder was hypomagnesaemic. Renal clearance tests showed that the administration of furosemide decreased distal fractional chloride reabsorption, while thiazide ingestion failed to decrease it. Genetic analysis identified six thiazide-sensitive Na-Cl co-transporter gene mutations, including two novel ones. Therefore, on the basis of the confirmatory renal clearance tests and mutational analysis, a diagnosis of Gitelman's syndrome was made in these patients.


CONCLUSIONS
Two of the five patients diagnosed with Gitelman's syndrome were normomagnesaemic, which is uncommon in this syndrome. Our study indicates that renal clearance tests and mutation analysis can play an important role in diagnosing Gitelman's syndrome more precisely.
Nakamura
Akinobu
A
Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Shimizu
Chikara
C
Nagai
So
S
Yoshida
Masahiro
M
Aoki
Kazutaka
K
Kondo
Takuma
T
Miyoshi
Hideaki
H
Wada
Norio
N
Tajima
Toshihiro
T
Terauchi
Yasuo
Y
Yoshioka
Narihito
N
Koike
Takao
T
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D053579:Gitelman Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D006801:Humans; D007677:Kidney Function Tests; D008274:Magnesium / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011955:Receptors, Drug / Q000235:genetics; D012083:Renin / Q000097:blood; D049992:Sodium Chloride Symporters / Q000235:genetics; D055815:Young Adult
D011955:Receptors, Drug; D049992:Sodium Chloride Symporters; C064415:thiazide receptor; D000450:Aldosterone; D012083:Renin; D008274:Magnesium