We report here the first case of Gitelman syndrome presenting with the biological features of Fanconi syndrome and an early severe polyuria since the neonatal period. In 1966 Gitelman et al. described a familial disorder in three adult female patients who presented with occasional episodes of muscle weakness and tetany . Neither polyuria nor growth retardation were observed. Hypokalemia, hypomagnesemia and hypocalciuria were the biochemical hallmarks of the disease. Since the initial report many cases have been described and the prevalence is estimated to be approximately 1 in 40.000 . Here, we describe a very atypical clinical and biological presentation of Gitelman syndrome in a 6 year old girl.
Most review articles and editorials present Gitelman syndrome as a disease with a relatively mild course, mostly discovered during routine investigations in adolescents or adult patients . Cruz et al. reported a cohort of 50 adults with Gitelman syndrome . Most patients being symptomatic, and the most common symptoms were musculoskeletal symptoms (such as cramps, muscle weakness and pain), generalized weakness and salt craving. Polyuria was observed in half of the patients. The authors defined polyuria as voiding at least five times during the daytime. Without quantitative measures, it seems difficult to evaluate the importance of polyuria, and therefore authors may have overestimated its prevalence. Regarding polydipsia, the daily intake in their adult patient cohort was (2.43 ± 1.28 L). Although these values are higher than fluid intake in controls (1.89 ± 0.42 L), it does not seem to be a very pronounced polydipsia for adult patients in whom the acceptable threshold limit for polydipsia is 3 L. Pathophysiologically, polyuria and polydipsia are less pronounced in GS than in classic Bartter syndrome, because only 7% of total salt reabsorption occurs in the distal tubule where the NCCT cotransporter involved in Gitelman syndrome is located. By contrast, in Bartter syndrome, the impaired reabsorption of sodium chloride involves the thick ascending limb of Henle which reabsorbs 30% of filtered NaCl and participates to the generation of the osmotic cortico-papillary gradient . This trend was described in the literature, and in the largest series of Gitelman syndrome [8–10] polyuria was either absent at diagnosis or was not a major symptom. In our case, marked polyuria and polydipsia starting from the neonatal period, with a daily intake of 3 L at the age of 6 years were the main clinical symptoms. As polyuria significantly decreased after the correction of kaliemia in our child, we hypothesized that a concentrating defect concomitant to the severe initial hypokalemia was an aggravating factor to the potentially mild polyuria due to sodium loss observed in Gitelman syndrome. Indeed hypokalemia is known to induce polydipsia and urinary concentration defect by downregulation of aquaporin-2 [11, 12].
The initial laboratory findings were more in favor of a proximal tubular defect (sodium and potassium losses, hypophosphatemia, renal tubular acidosis and hypouricemia with high fractional uric acid excretion). Although hypophosphatemia is not common in Gitelman syndrome, Vigano et al. showed that even if the bulk of phosphate is reabsorbed in the proximal tubule, there was a tendency towards renal phosphate wasting with mild to moderate hypophosphatemia in their cohort of 12 patients with Gitelman syndrome . In our patient hypophosphatemia was transient suggesting the importance of a long term follow-up of phosphate levels. The plasma acidosis and uric acid loss found initially in our patient could also be part of a tubular proximal defect secondary to the hypokalemia. Indeed, tubular proteinuria has been detected in patients with severe hypokalemia of different etiologies  and a transitory proximal dysfunction (tubular proteinuria, phosphaturia uricosuria and aminoaciduria) in patients with hypokalemia associated with renal tubular acidosis [15, 16] Nevertheless, as proximal dysfunction in distal renal tubular acidosis is corrected by alkali and potassium supplementation, a participation of acidosis in this dysfunction can not be excluded. Although tubular proteinuria and aminoaciduria were not assessed in our patient, we hypothesize that the transitory proximal dysfunction (acidosis, hypophosphatemia and hypouricemia) is secondary to the severe hypokalemia (1.6 mmol/l).
A few cases of Gitelman syndrome associated with glomerular or tubulointerstitial disease have been reported , but to date, no case associated to or with an initial profile of Fanconi syndrome have been described.