Flashcards in Inherited HTN Deck (27):
How does Syndrome of Apparent Mineralocorticoid Excess (AME) present?
Low birth weight
• Failure to thrive
• Severe hypertension in early childhood
• Extensive organ damage
• Renal failure
How does Syndrome of Apparent Mineralocorticoid Excess (AME) look clinically?
• Metabolic alkalosis
• Low plasma renin activity
• Low plasma aldosterone levels
What disease can AME look like?
Findings similar to primary aldosteronism
How do we diagnose AME?
In most patients with a defective enzyme, the urinary free cortisone levels are very low or undetectable.
Gene sequencing of the 11β-HSD2 gene is available to confirm the diagnosis.
How is AME inherited?
Autosomal recessive inheritance of rare mutation, often from consanguineous relationship
What is the pathogenesis of AME?
enzymatic defect in 11β-HSD2 which converts cortisol to cortisone
What is liddle syndrome also known as?
How does liddle syndrome look clinically?
•Hypertension-young onset, severe
•Low plasma renin activity
•Low plasma aldosterone AND urinary aldosterone
How is liddle syndrome inherited?
What is the mutation in liddle syndrome?
Gain-of-function mutation in the renal epithelial sodium channel (either beta or gamma subunit) leading to constitutive expression
What is the parthogenesis of liddle syndrome?
Increased absorption of sodium leads to hypertension
How do you diagnose liddle syndrome?
Gene sequencing of the SCNN1G and SCNN1B gene is available to confirm the diagnosis.
How do you treat AME?
• Therapy to reduce endogenous cortisol production (decrease sodium channel activity)--Amiloride & Triamterene
• Block mineral corticoid
receptor --Spironolactone & Eplerenone
• Potassium repletion
• Dexamethasone for ACTH suppression
What is the prognosis for AME?
usually poor because of advanced progression of disease at time of diagnosis
What is the treatment for liddle syndrome?
Agents that decrease sodium channel activity
What is the prognosis for liddle syndrome?
With treatment prognosis is good
• Without treatment cardiovascular and renal complications from uncontrolled hypertension often occur
How does Bartter syndrome present?
•Growth and mental retardation
•Polyuria & polydipsia
What would you find clinically in Bartter syndrome?
How does Gitelman syndrome present?
•Cramping of arms and legs
•Polyuria & nocturia
How are Gitelman and Bartter syndromes similar?
Autosomal recessive inheritance.
Pedigree may reveal affected sibs but not likely to be in previous generations
What transporter does Gitelman syndrome affect?
Na/Cl in early distal tubule
What area of the nephron does Bartter syndrome effect?
Thick ascending limb of the loop of Henle
What happens due to salt wasting?
hypotension which activates the RAAS activating ENaC which causes K secretion (hypokalemia) and H+ secretion (metabolic alkalosis)
Tubular defects in Bartter syndrome mimic what?
mimics chronic loop diuretic ingestion
What is the prognosis of Bartter syndrome?
Life expectancy reduced in severe cases, prognosis is poor
Tubular defects in Gitelman syndrome mimic what?
mimics chronic thiazide diuretic ingestion