The genetic spectrum of Gitelman(-like) syndromes.
Curr Opin Nephrol Hypertens
; 31(5): 508-515, 2022 09 01.
Article
en En
| MEDLINE
| ID: mdl-35894287
ABSTRACT
PURPOSE OF REVIEW Gitelman syndrome is a recessive salt-wasting disorder characterized by hypomagnesemia, hypokalemia, metabolic alkalosis and hypocalciuria. The majority of patients are explained by mutations and deletions in the SLC12A3 gene, encoding the Na+-Cl--co-transporter (NCC). Recently, additional genetic causes of Gitelman-like syndromes have been identified that should be considered in genetic screening. This review aims to provide a comprehensive overview of the clinical, genetic and mechanistic aspects of Gitelman(-like) syndromes. RECENT FINDINGS:
Disturbed Na+ reabsorption in the distal convoluted tubule (DCT) is associated with hypomagnesemia and hypokalemic alkalosis. In Gitelman syndrome, loss-of-function mutations in SLC12A3 cause impaired NCC-mediated Na+ reabsorption. In addition, patients with mutations in CLCKNB, KCNJ10, FXYD2 or HNF1B may present with a similar phenotype, as these mutations indirectly reduce NCC activity. Furthermore, genetic investigations of patients with Na+-wasting tubulopathy have resulted in the identification of pathogenic variants in MT-TI, MT-TF, KCNJ16 and ATP1A1. These novel findings highlight the importance of cell metabolism and basolateral membrane potential for Na+ reabsorption in the DCT.SUMMARY:
Altogether, these findings extend the genetic spectrum of Gitelman-like electrolyte alterations. Genetic testing of patients with hypomagnesemia and hypokalemia should cover a panel of genes involved in Gitelman-like syndromes, including the mitochondrial genome.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Bartter
/
Alcalosis
/
Síndrome de Gitelman
/
Hipopotasemia
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Curr Opin Nephrol Hypertens
Asunto de la revista:
ANGIOLOGIA
/
NEFROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania