Gitelman Syndrome

Snapshot

• An 8-year-old girl is brought to the pediatrician for evaluation of increased urinary frequency. She has muscle cramps and fatigue. She is found to be normotensive. Laboratory exam reveals hypomagnesemia, hypokalemia, and a mild metabolic alkalosis.

Introduction

• Clinical definition
  • a renal tubular defect affecting the distal convoluted tubules characterized by
    • mild hypokalemia
    • mild metabolic alkalosis
    • significant hypomagnesemia
    • normal blood pressure
• Epidemiology
  • incidence
    • rare
    • 1:40,000
  • demographics
    • detected in young children but can be detected in adulthood
  • risk factors
    • consanguinity
• Pathogenesis 
  • mutation involving NaCl cotransporter (NCTT) which results in
    • impaired Na⁺ reabsorption in distal convoluted tubule
• Genetics
  • inheritance pattern
    • autosomal recessive
  • mutations
    • chromosome
• SLC12A3 gene

Presentation

• Symptoms
  • polyuria
  • polydipsia
  • muscle weakness or cramp
  • fatigue
  • paresthesias
  • abdominal pain
  • vomiting
• Physical exam
• growth is often normal but can be delayed

Studies

• Labs
  • hypokalemia (lower than in Bartter’s)
  • hypomagnesemia
  • metabolic alkalosis
  • genetic testing
    • most definitive diagnosis
• Urine studies
• ↓ Ca2+

Differential

• Bartter’s syndrome
  • normal serum magnesium

Renal Tubular Defects
Category	Fanconi Syndrome	Bartter Syndrome	Gitelman Syndrome	Liddle Syndrome
Defect localization	Proximal tubule	Thick ascending loop of Henle	Distal convoluted tubule	Collecting tubule
Etiology	Wilson diseaseTyrosinemiaCystinosisMultiple myelomaGalactosemiaMitochondrial myopathiesMedicationsaminoglycosidescisplatinifosfamidevalproic acidHeavy metalsmercury lead	Autosomal recessive mutation involving the NKCC2 cotransporter	Autosomal recessive mutation involving the NaCl cotransporter	Autosomal dominant mutation leading to increased activity of epithelial Na+ channel (ENaC)
Findings	HypophosphatemiaAminoaciduriaRenal glucosuriaTubular proteinuriaProximal renal tubular acidosis	HypokalemiaHypochloremiaMetabolic alkalosisNormotensionElevated plasma renin level	HypokalemiaHypochloremiaMetabolic alkalosisHypomagnesemiaHypocalciuriaNormotension	HypertensionHypokalemiaMetabolic alkalosis

Treatment

• Conservative
  • optimize electrolytes with diet or supplements
    • indications
      • those with hypokalemia or hypomagnesemia
• Medical
  • nonsteroidal anti-inflammatory drugs (NSAIDs)
    • indications
      • for patients who require medical therapy beyond dietary supplements
    • drugs
      • indomethacin
      • celecoxib
  • potassium-sparing diuretics
    • indications
      • to treat hypokalemia and metabolic alkalosis
    • drugs
      • amiloride
• eplerenone

Complications

• Cardiac arrhythmia due to hypomagnesemia and hypokalemia
• Chondrocalcinosis