ABSTRACT
El síndrome de Gitelman es una tubulopatía de herencia autosómica recesiva debida a mutaciones inactivantes en el gen SLC12A3 que codifica para el cotransportador sodio-cloro (NCC). El NCC es una proteína de membrana que pertenece a la familia de transportadores SLC12 cloro-catiónicos que constituye la principal vía de reabsorción de sodio y cloro (NaCl), determina la presión arterial y es el lugar de acción de los diuréticos tipo tiazida. El síndrome de Gitelman se caracteriza por hipopotasemia, hipomagnesemia, alcalosis metabólica, normocalcemia e hipocalciuria. El diagnóstico diferencial se realiza con el síndrome de Bartter tipoiii y la hipomagnesemia renal con hipocalciuria. Puede ser asintomático o expresarse con síntomas leves (calambres, fatiga o dolor articular) o con síntomas más graves (tetania, convulsiones). A pesar de considerarse benigno, la combinación de hipopotasemia con hipomagnesemia puede prolongar el intervalo QT y desencadenar arritmias que pueden amenazar la vida del paciente. Por todo ello resulta importante el diagnóstico diferencial y la confirmación mediante el estudio genético de cara al seguimiento de los pacientes y al asesoramiento genético (AU)
Gitelman syndrome, an autosomal recessive tubulopathy, is caused by inactivating mutations in SLC12A3 gene. This gene codes for the sodium chloride co-transporter (NCC), a membrane protein that belongs to the family of SLC12 chloride-cationic transporters. NCC constitutes the main route of sodium chloride (NaCl) reabsorption, determines blood pressure, and is the site of action of thiazide-type diuretics. Gitelman syndrome usually involves hypokalaemia, hypomagnesaemia, metabolic alkalosis, and hypocalciuria. The differential diagnosis for Gitelman syndrome includes Bartter syndrome typeiii and renal hypomagnesaemia. Symptoms reported in the literature range from asymptomatic, to mild symptoms of cramps and fatigue, to severe manifestations such as tetany and seizures. The prognosis is generally good, but a few patients with hypokalaemia and hypomagnesaemia may have a prolonged QT interval and trigger potentially life-threatening arrhythmias. Thus, genetic testing is important to confirm the diagnosis, as well as in the follow-up of patients (AU)
Subject(s)
Humans , Female , Child, Preschool , Gitelman Syndrome/diagnosis , Gitelman Syndrome/pathology , Hypokalemia/diagnosis , Perfusion , Electrolytes/therapeutic use , Serum/chemistry , Solute Carrier Family 12, Member 3/analysis , Diagnosis, Differential , Renal Tubular Transport, Inborn Errors/diagnosisABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Patients with non-alcoholic steatohepatitis (NASH) have increased plasmatic and hepatic concentrations of bile acids (BA), suggesting that they can be associated with the progression of the disease. Hepatic nuclear receptors are known to modulate genes controlling BA metabolism; thus, in this work we aimed to compare the expression of liver nuclear receptors -farnesoid X (FXR), small heterodimer partner (SHP) and liver X alpha (LXRα) receptors- and BA transporters -sodium+/taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP)- in liver biopsy samples of patients with simple steatosis (SS) and NASH. MATERIAL AND METHODS: Forty patients with biopsy-proven NALFD were enrolled between 2009 and 2012; liver biopsies were classified as SS (N = 20) or NASH (N = 20) according to the NAFLD activity score. Gene expression of nuclear FXR, LXRα, SHP, NTCP and BSEP was analyzed by real-time reverse transcription polymerase chain reaction and protein level was quantified by western blot. RESULTS: Gene expression of FXR, SHP, NTCP and BSEP was significantly up-regulated in the NASH group in comparison with SS patients (P < 0.05). In contrast, protein level for FXR, SHP and NTCP was decreased in the NASH patients vs. the SS group (P < 0.05). Gene and protein profile of LXRα did not show differences between groups. CONCLUSIONS: The results suggest that liver nuclear receptors (FXR and SHP) and BA transporters (NTCP and BSEP) are associated with the progression of NAFLD.