Clinical Characteristics, Symptoms, and Long-Term Outcomes in Gitelman Syndrome

Abstract

Genetics; Hypokalemia; Hypomagnesemia

Genética; Hipopotasemia; Hipomagnesemia

Genètica; Hipopotassèmia; Hipomagnesèmia

Introduction Gitelman syndrome (GS) is a rare inherited salt-losing tubulopathy with limited clinical data. Methods Surveys were conducted with GS physicians in Europe and patients with GS in the Netherlands to compare findings with the general population. Results Data from 587 patients (25% pediatric) across 13 countries showed 93% were genotyped, with 94% having variants in SLC12A3. Children with GS were shorter and lighter than the general population, with lower bodyweight persisting into adulthood. The sex distribution was uneven, with more males in childhood and more females in adulthood. Patients with GS had the expected electrolyte disorders as well as significantly lower blood phosphate levels. Positive correlations were found between blood magnesium and potassium, and potassium and aldosterone. Physicians reported muscle cramps, salt craving, and muscle weakness as most common GS symptoms. Patients with GS scored worse than the general population in fatigue, physical, and cognitive function; and ranked salt craving and polydipsia-polyuria as the most severe symptoms. Symptom burden was higher in adult females and patients with lower blood magnesium. Treatment mainly consisted of potassium (94%) and magnesium (50%) supplementation. Potassium-sparing medication (used in 33%) slightly increased blood potassium levels (3.2 vs. 3.1 mmol/l). Adult patients with GS had a high prevalence of chondrocalcinosis (15%) and elevated blood cell counts (26%). Compared with the general population, adult patients with GS had lower rates of chronic kidney disease (CKD) and hypertension, a similar rate of diabetes, but a higher rate of albuminuria or proteinuria (28%). Conclusions These findings provide new insights into GS, highlight disease burden, and suggest areas for future research.