Inherited HTN

Question 1

How does Syndrome of Apparent Mineralocorticoid Excess (AME) present?

Answer 1

Low birth weight
• Failure to thrive
• Severe hypertension in early childhood
• Extensive organ damage 
• Renal failure

Question 2

How does Syndrome of Apparent Mineralocorticoid Excess (AME) look clinically?

Answer 2

• Hypertension
• Hypokalemia
• Metabolic alkalosis
• Low plasma renin activity
• Low plasma aldosterone levels

Question 3

What disease can AME look like?

Answer 3

Findings similar to primary aldosteronism

Question 4

How do we diagnose AME?

Answer 4

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.

Question 5

How is AME inherited?

Answer 5

Autosomal recessive inheritance of rare mutation, often from consanguineous relationship

Question 6

What is the pathogenesis of AME?

Answer 6

enzymatic defect in 11β-HSD2 which converts cortisol to cortisone

Question 7

What is liddle syndrome also known as?

Answer 7

Pseudoaldosteronism

Question 8

How does liddle syndrome look clinically?

Answer 8

• Hypertension-young onset, severe
• Hypokalemia
• Metabolic Alkalosis
• Low plasma renin activity
• Low plasma aldosterone AND urinary aldosterone

Question 9

How is liddle syndrome inherited?

Answer 9

autosomal dominant

Question 10

What is the mutation in liddle syndrome?

Answer 10

Gain-of-function mutation in the renal epithelial sodium channel (either beta or gamma subunit) leading to constitutive expression

Question 11

What is the parthogenesis of liddle syndrome?

Answer 11

Increased absorption of sodium leads to hypertension

Question 12

How do you diagnose liddle syndrome?

Answer 12

Gene sequencing of the SCNN1G and SCNN1B gene is available to confirm the diagnosis.

Question 13

How do you treat AME?

Answer 13

• Therapy to reduce endogenous cortisol production (decrease sodium channel activity)--Amiloride & Triamterene
• Block mineral corticoid 
receptor --Spironolactone & Eplerenone
• Potassium repletion
• Dexamethasone for ACTH suppression

Question 14

What is the prognosis for AME?

Answer 14

usually poor because of advanced progression of disease at time of diagnosis

Question 15

What is the treatment for liddle syndrome?

Answer 15

Agents that decrease sodium channel activity
• Amiloride
• Triamterene

Question 16

What is the prognosis for liddle syndrome?

Answer 16

With treatment prognosis is good

• Without treatment cardiovascular and renal complications from uncontrolled hypertension often occur

Question 17

How does Bartter syndrome present?

Answer 17

Presentation:
•Early childhood
•Growth and mental retardation
•Polyuria & polydipsia
•Hypercalciuria

Question 18

What would you find clinically in Bartter syndrome?

Answer 18

Clinical Picture:
•Hypokalemia 
•Hyperreninemia
•Hyperaldosteronism
•Metabolic alkalosis

Question 19

How does Gitelman syndrome present?

Answer 19

Presentation:
•Adolescence/Adulthood
•Cramping of arms and legs
•Fatigue
•Hypomagnesemia
•Polyuria & nocturia

Question 20

How are Gitelman and Bartter syndromes similar?

Answer 20

Autosomal recessive inheritance.

Pedigree may reveal affected sibs but not likely to be in previous generations

Question 21

What transporter does Gitelman syndrome affect?

Answer 21

Na/Cl in early distal tubule

Question 22

What area of the nephron does Bartter syndrome effect?

Answer 22

Thick ascending limb of the loop of Henle

Question 23

What happens due to salt wasting?

Answer 23

hypotension which activates the RAAS activating ENaC which causes K secretion (hypokalemia) and H+ secretion (metabolic alkalosis)

Question 24

Tubular defects in Bartter syndrome mimic what?

Answer 24

mimics chronic loop diuretic ingestion

Question 25

What is the prognosis of Bartter syndrome?

Answer 25

Life expectancy reduced in severe cases, prognosis is poor

Question 26

Tubular defects in Gitelman syndrome mimic what?

Answer 26

mimics chronic thiazide diuretic ingestion

Question 27

What is the prognosis for Gitelman syndrome?

Answer 27

Prognosis is good with proper treatment