Gitelman Syndrome

Gitelman Syndrome

Giovanni Briganti

• Male, 42 years old Swiss• High Level of Stress• Sweat• Potassium Check• Cramps, Tetany

At the ER…

• Familial Hypokalemia – Hypomagnesemia

• Autosomal Recessive• Salt Losing Renal Tubulopathy• Aldosteronism • 1/40.000

Definitions

• Mutation SLC12A3 gene• Sodium Chloride transporter NCC

Etiopathogenesis 1

• 1021 aa • 12 transmembrane domains• 140 putative mutations• Loss of function

Thiazide-sensitive NCC

• Xenopus leavis oocytes• Type 2 mutation (partial) :

Misfolding – ER Retention – Rapid Degradation

• Chaperones?• Regulator – 4-phenylbutyrate

Etiopathogenesis 2

Xenopus leavis

• Basolateral membrane• Transmbembrane potential • Loss of function CLCNKB gene• Bartter Syndrome• Screening

ClC-Kb Channel

Etiopathogenesis 3

Loss of Na, Cl-

Aldosterone Production SRAA

ENaC activation

K+ and H+ Loss

Hypokalemia and Alkalosis

Nephron

Renal Corpuscle

Aldosteronism

What about Mg2+?

• Adult• Fatigue• Weakness• Cramps• Paresthesia (Facial)• Tetany• Ventricular Arrythmia Cardiac Arrest• Prolonged QT interval (50%)

Clinical Description

Tetany

Blood test - Arterial Gazometry- ECG • Hypokalemia (2.7 +- 0,4 mmol/L)• Hypomagnesemia (< 0,65 mmol)• Metabolic AlkalosisDD also include Bartter type 3

Diagnosis

• K+, Mg2+, symptoms evaluation • MgCl2 4mg/kg/24hrs orally• 3-4 administration (diarrhea)• Acute tetany 20% MgCl2 every 6 hrs• Amiloride ENaC (avoid K+ ejection)

Management / Treatment

• 25% of chance• Autosomal recessive

Genetic Counseling

• Excellent• Daily Activities vs Fatigue

Prognosis

Thank you for coming !

Human Physiology, An Integrated Approach Guyton Medical Physiology Orphanet Journal of Rare Diseases 2008, 3:22

doi:10.1186/1750-1172-3-22

Sources