What are the differences between Bartter syndrome, Gitelman syndrome, and Liddle syndrome?

From the Guidelines

Bartter, Gitelman, and Liddle syndromes are distinct genetic disorders affecting kidney function, primarily differentiated by their electrolyte abnormalities, genetic causes, and clinical presentations, with Bartter syndrome presenting with hypokalemia, metabolic alkalosis, and elevated urinary chloride and calcium, Gitelman syndrome presenting with hypomagnesemia and hypocalciuria, and Liddle syndrome presenting with hypertension and suppressed renin and aldosterone levels. The primary characteristics of these syndromes include:

• Bartter syndrome: hypokalemia, metabolic alkalosis, normal to low blood pressure, and elevated urinary chloride, calcium, and prostaglandins, typically manifesting in childhood with growth retardation, polyuria, and sometimes nephrocalcinosis 1.
• Gitelman syndrome: shares features with Bartter but typically presents later in life with milder symptoms, distinctive hypomagnesemia, hypocalciuria, and mutations in the thiazide-sensitive sodium-chloride cotransporter 1.
• Liddle syndrome: causes hypertension, hypokalemia, metabolic alkalosis, and suppressed renin and aldosterone levels due to mutations causing constitutive activation of epithelial sodium channels 1. The treatment for these syndromes differs significantly based on the underlying pathophysiology:
• Bartter syndrome: treatment includes potassium supplementation, NSAIDs, and potassium-sparing diuretics 1.
• Gitelman syndrome: treatment focuses on magnesium and potassium supplementation 1.
• Liddle syndrome: treatment involves amiloride or triamterene, which directly block the epithelial sodium channels, rather than spironolactone which would be ineffective due to the already low aldosterone levels 1. Understanding these distinctions is crucial for proper diagnosis and management, as the treatments differ significantly based on the underlying pathophysiology of each syndrome.

From the Research

Differentiation of Bartter, Gitelman, and Liddle Syndrome

• Bartter syndrome and Gitelman syndrome are two renal tubular disorders characterized by sodium and potassium wasting, as discussed in 2 and 3.
• The clinical features of Bartter syndrome and Gitelman syndrome can be distinguished based on their pathophysiology, with Bartter syndrome affecting the thick ascending limb of Henle's loop and Gitelman syndrome affecting the distal convoluted tubule, as explained in 3.
• Liddle syndrome, on the other hand, is characterized by excess aldosterone, which stimulates the collecting duct mineralocorticoid receptor (MR) to upregulate the epithelial sodium channel (ENaC) and stimulate electrogenic sodium reabsorption, with secretion of potassium and protons, as described in 4.
• The differentiation between Bartter, Gitelman, and Liddle syndrome can be based on clinical characteristics, such as age at diagnosis, sex, body mass index, estimated glomerular filtration rate, and serum and urine electrolyte concentrations, as discussed in 5.
• Additionally, the presence of hypomagnesemia and hypocalciuria can be used to differentiate between Gitelman syndrome and other conditions, as noted in 5.
• A dietary approach to the treatment of Gitelman's and Bartter's syndromes, including potassium, sodium, chloride, and magnesium supplementation, can also be considered, as discussed in 6.
• The correct physiologic and pharmacologic characterization of these syndromes is essential for a sound diagnostic and therapeutic patient management, as emphasized in 3.