Gitelman syndrome was described originally in 1966 by dr. Hillel Gitelman as a syndrome of hypokalemia and hypomagnesemia, it was associated with metabolic alkalosis and RAAS activation:
https://t.co/No8k7WkRxS
The symptoms of Gitelman can be quite diverse, as summarized by Devuyst and colleagues: https://link.springer.com/referenceworkentry/10.1007/978-3-662-43596-0_34
In 1996 the group of dr. Rick Lifton identified mutations SLC12A3 encoding the Na-Cl-co-transporter (NCC) as cause for Gitelman syndrome. Nice detail: the paper still refers to NCC as TSC (thiaizide-sensitive co-transporter): https://www.nature.com/articles/ng0196-24
NCC Function
Since its identification, the function of NCC is widely studied. This animation demonstrates its activation by phosphorylation and its inhibition by thiazides.
Regulation of NCC by potassium has been widely studied to understand its role in blood pressure, potassium handling and salt sensitivity. Nicely reviewed by David Ellison and Paul Welling: https://www.nejm.org/doi/full/10.1056/NEJMra2030212 and by Ewout Hoorn: https://journals.physiology.org/doi/full/10.1152/physrev.00044.2018?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
Genetics
Key molecules in this potassium switch mechanisms have also been implicated in Mendelian disorders. Mutations in KCNJ10, KCNJ16, CLCNKB, ATP1A1 and FXYD2 result in a Gitelman-like electrolyte phenotype. Last year, we demonstrated that also mitochondrial DNA variants cause a Gitelman-like phenotype.
Also the phenotype of Gitelman syndrome has been more carefully analyzed recently, demonstrating: Insulin resistance: https://journals.lww.com/JASN/Abstract/2019/08000/Resistance_to_Insulin_in_Patients_with_Gitelman.21.aspx…
Low phosphate: https://academic.oup.com/ndt/article/37/12/2474/6523371?login=true… Immunodeficiency: https://nature.com/articles/s41467-020-18184-3…
Treatment
The treatment of Gitelman syndrome is still largely dependent on oral Mg and K supplements. KDIGO published an expert opinion in the diagnosis and management of Gitelman patients:
https://www.sciencedirect.com/science/article/pii/S0085253816306020?via%3Dihub
For more information on the genetics of Gitelman, check the rare disease databases.
OMIM: https://omim.org/entry/263800
Orphanet: https://orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=358…
This text was adapted from Twitter:
Kidney Physiology 