✅ Model Answer:
• Diagnosis: Pseudohypoaldosteronism type I (PHA1) – autosomal recessive (ENaC mutation – SCNN1A, SCNN1B, SCNN1G) or autosomal dominant (NR3C2 – mineralocorticoid receptor mutation).
• Evidence: Hyperkalemia, hyponatremia, metabolic acidosis, salt wasting, normal BP, elevated renin and aldosterone (resistant to mineralocorticoid effect).
• Next step: Genetic testing (SCNN1A, SCNN1B, SCNN1G, NR3C2). Sodium supplementation (1-2 mEq/kg/day, up to 10-20 mEq/kg/day in severe cases), kayexalate (sodium polystyrene sulfonate) for hyperkalemia, sodium bicarbonate for acidosis. Fludrocortisone is ineffective. Monitor electrolytes and growth.

✅ Model Answer:
• Two forms:
- Autosomal dominant (renal PHA1): NR3C2 (mineralocorticoid receptor) mutation – milder, typically affects only the kidney.
- Autosomal recessive (systemic PHA1): SCNN1A, SCNN1B, SCNN1G (ENaC subunits) mutations – severe, affects kidney, lung, and sweat glands.
• Pathophysiology:
- ENaC loss-of-function: Impaired Na reabsorption in the distal nephron → salt wasting, volume contraction, hyperkalemia, metabolic acidosis. Compensatory hyperreninemia and hyperaldosteronism are ineffective.
- NR3C2 mutations: Aldosterone resistance at the receptor level.
• Prevalence: Rare (autosomal recessive <1 in 1,000,000).
• Systemic PHA1: Also causes pseudohypoaldosteronism in other tissues (e.g., lungs – recurrent respiratory infections, sweat glands – salt wasting).

✅ Model Answer:
• Classic features:
- Neonatal/infancy onset: Failure to thrive, poor feeding, vomiting, severe dehydration.
- Hyperkalemia: Often life-threatening (>6.5 mEq/L), arrhythmias.
- Hyponatremia: Salt wasting.
- Metabolic acidosis.
- Normal blood pressure.
- Elevated renin and aldosterone (resistant).
- Frequent hospitalizations.
• Systemic PHA1 (ENaC mutations):
- Respiratory: Recurrent pneumonia, wheezing (due to defective Na transport in airway epithelium).
- Skin: Salt loss in sweat → heat intolerance.
- Growth: Poor growth despite treatment.
• Renal PHA1 (NR3C2): Milder, responds partially to fludrocortisone, improves with age.

✅ Model Answer:
• Biochemical:
- Serum K: Elevated (>5.5 mEq/L).
- Serum Na: Low (<135 mEq/L).
- HCO3: Low (metabolic acidosis).
- Plasma renin: Elevated.
- Plasma aldosterone: Elevated (inappropriately high for hyperkalemia/hyponatremia).
- Urine Na: Elevated (salt wasting).
- Urine K: Low (despite hyperkalemia).
- 17-OHP: Normal (exclude CAH).
• Response to fludrocortisone: No improvement (PHA1) – differentiates from mineralocorticoid deficiency.
• Genetic testing: SCNN1A, SCNN1B, SCNN1G, NR3C2 (confirmatory).
• Renal ultrasound: Normal (no obstruction).
• Electrocardiogram: For hyperkalemia (peaked T waves).

✅ Model Answer:
• Sodium supplementation:
- Oral NaCl: 1-2 mEq/kg/day (up to 10-20 mEq/kg/day in severe systemic PHA1).
- IV NaCl: For acute dehydration or hyperkalemia.
• Hyperkalemia management:
- Kayexalate (sodium polystyrene sulfonate): 0.5-1 g/kg/dose PO/PR (binds K).
- Avoid: Potassium-containing fluids, potassium-sparing diuretics.
• Acidosis: Sodium bicarbonate (1-2 mEq/kg IV or PO).
• Fludrocortisone: Ineffective (PHA1 is resistant).
• Nutritional support: Ensure adequate calories and growth.
• Monitor: Serum electrolytes, BP, weight, growth.
• Systemic PHA1: May require higher sodium doses and respiratory support.

✅ Model Answer:
• Hyperkalemia: Arrhythmias, cardiac arrest (especially in neonates).
• Severe dehydration: Recurrent, life-threatening, failure to thrive.
• Growth failure.
• Metabolic acidosis: Can cause poor feeding, vomiting.
• Renal: Nephrocalcinosis (rare).
• Respiratory: Recurrent infections (systemic PHA1).
• Psychosocial: Impact of frequent hospitalizations and chronic illness.
• Outcome: Autosomal dominant (renal) improves with age; systemic (ENaC) is lifelong.

✅ Model Answer:
• Prognosis:
- Autosomal dominant (renal): Improves with age; may not require lifelong treatment.
- Autosomal recessive (systemic): Lifelong, requires aggressive sodium supplementation and monitoring.
- Quality of life: Good with treatment; can lead normal lives.
- Life expectancy: Normal with appropriate management.
- Growth: Can be normal with adequate sodium and nutrition.
• Long-term follow-up:
- Monitor electrolytes, BP, growth.
- Monitor for hyperkalemia and dehydration.
- Genetic counseling.
- Education: Recognize signs of dehydration/hyperkalemia, avoid potassium-rich foods.

✅ Model Answer:
• PHA1:
- Renin: Elevated.
- Aldosterone: Elevated.
- Salt wasting: Yes.
- Hyperkalemia: Yes.
- Response to fludrocortisone: No (resistant).
- Genetics: ENaC or MR mutation.
- BP: Normal.
• Aldosterone synthase deficiency (CYP11B2):
- Renin: Elevated.
- Aldosterone: Low.
- Salt wasting: Yes.
- Hyperkalemia: Yes.
- Response to fludrocortisone: Yes (corrects).
- Genetics: CYP11B2 mutation.
- BP: Normal.