From the Research
Gitelman syndrome primarily affects the thiazide-sensitive sodium-chloride cotransporter (NCC or NCCT) located in the distal convoluted tubule of the kidney, as evidenced by the most recent study 1. This transporter, encoded by the SLC12A3 gene, is responsible for reabsorbing sodium and chloride from the tubular fluid back into the bloodstream. When mutations occur in the SLC12A3 gene, the function of the NCC transporter is impaired, leading to the characteristic features of Gitelman syndrome. The reduced activity of this transporter results in increased sodium and chloride excretion in the urine, which subsequently causes hypokalemia (low potassium), metabolic alkalosis, hypomagnesemia (low magnesium), and hypocalciuria (decreased calcium excretion). This is similar to the effect seen with thiazide diuretics, which pharmacologically inhibit the same transporter, as noted in a study from 2. Understanding this specific transporter defect explains why patients with Gitelman syndrome require lifelong supplementation with potassium and magnesium, and why they typically have normal or low blood pressure despite salt wasting, as discussed in 3 and 4. Key aspects of Gitelman syndrome include:
- Hypokalemic metabolic alkalosis
- Hypomagnesemia
- Hypocalciuria
- Normal or low blood pressure
- Requirement for lifelong potassium and magnesium supplementation
- Similarity to the effect of thiazide diuretics on the NCC transporter, as seen in 5. Overall, the thiazide-sensitive sodium-chloride cotransporter (NCC) plays a crucial role in the pathophysiology of Gitelman syndrome, and its impairment leads to the characteristic electrolyte and acid-base abnormalities associated with the disease, as supported by the latest research 1.