✅ Model Answer:
• Diagnosis: Cystinuria (SLC3A1 or SLC7A9 mutation).
• Evidence: Recurrent renal stones, hexagonal crystals on urinalysis, normal serum electrolytes, history of renal colic.
• Next step: Genetic testing (SLC3A1, SLC7A9). Confirm with 24-hour urine cystine excretion (elevated). Start high fluid intake (>3 L/day), alkalinization (potassium citrate to maintain urine pH >7.0), and tiopronin or D-penicillamine if refractory. Monitor for stone recurrence and renal function.

✅ Model Answer:
• Genes:
- Type A (most common): SLC3A1 (rBAT) – encodes the heavy subunit of the amino acid transporter – located on chromosome 2p21.
- Type B: SLC7A9 (b0,+AT) – encodes the light subunit – located on chromosome 19q13.
- Type AB: Compound heterozygotes (one mutation in each gene).
• Inheritance: Autosomal recessive (SLC3A1, SLC7A9).
• Prevalence: 1 in 7,000 (most common inherited cause of renal stones).
• Pathophysiology: Defective transport of cystine, lysine, arginine, and ornithine in the proximal tubule → impaired reabsorption → increased urinary excretion of these amino acids. Cystine is poorly soluble in urine → precipitates to form hexagonal crystals and stones.
• Types: Type I (SLC3A1 – true autosomal recessive), Type II (SLC7A9 – more severe), Type III (SLC7A9 – less severe).

✅ Model Answer:
• Classic features:
- Recurrent renal stones: Often radiopaque (calcium-containing) or radiolucent (pure cystine stones).
- Renal colic: Flank pain, hematuria, dysuria.
- Hexagonal crystals on urinalysis (pathognomonic).
- Recurrent urinary tract infections.
- Obstruction: Hydronephrosis, acute kidney injury.
- Age: Usually presents in childhood or adolescence (peak 10-20 years).
- Family history.
• Other: May be asymptomatic (incidental finding on imaging).

✅ Model Answer:
• Urinalysis: Hexagonal crystals (pathognomonic).
• 24-hour urine cystine excretion: >250 mg/day (or >100 mg/L) confirms diagnosis.
• Stone analysis: Cystine composition (if stones are passed or removed).
• Urine amino acid chromatography: Elevated cystine, lysine, arginine, ornithine.
• Serum: Normal electrolytes, creatinine, calcium, PTH, uric acid (to rule out other causes).
• Renal imaging: Ultrasound/CT – stones, hydronephrosis.
• Genetic testing: SLC3A1 and SLC7A9 (confirmatory).
• Family screening: First-degree relatives (autosomal recessive).

✅ Model Answer:
• High fluid intake: >3 L/day (urine output >2-3 L/day) to keep cystine concentration <200 mg/L.
• Alkalinization: Potassium citrate (or sodium bicarbonate) to maintain urine pH >7.0 (cystine solubility increases at pH >7.0).
• Dietary modification: Low sodium diet (<2 g/day), moderate protein intake (avoid methionine-rich foods – meat, fish, dairy).
• Cystine-binding agents (if refractory):
- Tiopronin (Thiola): 15-20 mg/kg/day (divided q8h) – converts cystine to a soluble mixed disulfide.
- D-penicillamine: 10-20 mg/kg/day (divided q6h) – but more side effects (nephrotic syndrome, rash, cytopenias).
• Alpha-lipoic acid: Limited evidence.
• Stone removal: Extracorporeal shock wave lithotripsy (ESWL), ureteroscopy, or percutaneous nephrolithotomy (PCNL) for large stones.
• Monitor: Urine pH, cystine excretion, stone recurrence, renal function.
• Genetic counseling.

✅ Model Answer:
• Recurrent nephrolithiasis: Frequent stone formation → obstruction, infection, pain.
• Hydronephrosis: Obstruction of the ureter → acute kidney injury (AKI) or chronic kidney disease (CKD).
• Urinary tract infections: Due to obstruction and stasis.
• Chronic kidney disease: Progressive renal impairment (if recurrent obstruction).
• End-stage kidney disease (ESKD): In severe, untreated cases.
• Psychosocial impact: Recurrent hospitalizations, pain, dietary restrictions.
• Drug side effects: D-penicillamine (nephrotic syndrome, rash, cytopenias, lupus-like reaction).

✅ Model Answer:
• Prognosis:
- Variable: Depends on adherence to therapy.
- With treatment: Good control of stone recurrence.
- Without treatment: Frequent stones, CKD, and ESKD.
- Quality of life: Good with compliance; may be affected by recurrent symptoms.
- Life expectancy: Normal with treatment.
• Long-term follow-up:
- Monitor urine pH and cystine excretion.
- Monitor renal function (eGFR, creatinine).
- Monitor for stone recurrence (imaging).
- Dietary counseling.
- Genetic counseling.
- Screen for complications.

✅ Model Answer:
• Mechanism: Cystine solubility is pH-dependent. At urine pH <6.0, cystine is poorly soluble and precipitates. At pH >7.0, cystine solubility increases significantly (up to 250-500 mg/L).
• Goal: Maintain urine pH >7.0 (ideally 7.0-7.5) to keep cystine dissolved.
• Agents:
- Potassium citrate: Preferred (also provides potassium, reduces calcium excretion).
- Sodium bicarbonate: Alternative, but may increase sodium load.
• Monitoring: Regular urine pH measurement (at home with pH strips).
• Dose: Titrate to achieve pH >7.0 (usually 1-3 mEq/kg/day).
• Side effects: Hyperkalemia (with potassium citrate), metabolic alkalosis (if overdosed).