✅ Model Answer:
• Diagnosis: Fanconi syndrome (generalized proximal tubule dysfunction).
• Evidence: Low molecular weight proteinuria, glycosuria (normal serum glucose), phosphaturia (hypophosphatemia), aminoaciduria, proximal renal tubular acidosis (low bicarbonate), genu varum (rickets), failure to thrive.
• Next step: Evaluate for underlying cause – most common is cystinosis (check WBC cystine level). Treat underlying cause (cysteamine for cystinosis). Replace electrolytes: phosphate, bicarbonate, potassium, vitamin D/calcitriol for rickets.

✅ Model Answer:
• Definition: A generalized dysfunction of the proximal renal tubule leading to impaired reabsorption of glucose, phosphate, amino acids, bicarbonate, uric acid, and low molecular weight proteins.
• Causes:
- Primary (inherited):
• Cystinosis (most common in children).
• Galactosemia, hereditary fructose intolerance, tyrosinemia, Wilson disease, Lowe syndrome.
- Secondary (acquired):
• Drugs (tenofovir, ifosfamide, valproic acid, aminoglycosides).
• Heavy metal toxicity (lead, mercury).
• Vitamin D deficiency.
• Multiple myeloma (in adults).
- Idiopathic.
• Consequences: Failure to thrive, rickets (hypophosphatemia), metabolic acidosis, dehydration.

✅ Model Answer:
• Classic features:
- Failure to thrive (poor weight gain, growth failure).
- Rickets/osteomalacia: Genu varum, bone pain, waddling gait (due to phosphate wasting and vitamin D deficiency).
- Polyuria, polydipsia (glycosuria, salt wasting).
- Dehydration (salt and water loss).
- Proximal RTA: Metabolic acidosis (low bicarbonate, non-anion gap acidosis).
- Proteinuria: Low molecular weight proteins (β2-microglobulin, retinol-binding protein).
- Glycosuria (normal serum glucose).
- Phosphaturia (hypophosphatemia).
- Aminoaciduria.
- Hypokalemia (potassium wasting).
• Age: Depends on underlying cause; cystinosis presents in infancy/early childhood.

✅ Model Answer:
• Urine studies:
- Low molecular weight proteinuria: β2-microglobulin, retinol-binding protein, α1-microglobulin.
- Glycosuria (normal serum glucose).
- Phosphaturia (low serum phosphate).
- Aminoaciduria (generalized).
- Urine pH: Usually >5.5 (if proximal RTA).
- Urine calcium: Often low.
• Serum studies:
- Hypophosphatemia.
- Hypokalemia.
- Metabolic acidosis (low bicarbonate).
- Normal serum glucose (excludes diabetes).
- Alkaline phosphatase: Elevated (if rickets).
• Imaging: X-rays – rickets (cupping, fraying, bowing).
• Genetic testing: For inherited causes (e.g., CTNS for cystinosis).
• WBC cystine level: For cystinosis (most common cause in children).

✅ Model Answer:
• Treat the underlying cause:
- Cystinosis: Cysteamine (depletes cystine).
- Galactosemia: Lactose-free diet.
- Hereditary fructose intolerance: Fructose-free diet.
- Drug-induced: Withdraw the offending drug.
• Electrolyte replacement:
- Phosphate supplementation: 20-40 mg/kg/day of elemental phosphorus.
- Vitamin D/calcitriol: For rickets (0.01-0.1 mcg/kg/day).
- Bicarbonate: For proximal RTA (1-3 mEq/kg/day).
- Potassium supplementation: For hypokalemia.
- Salt supplementation: If salt wasting.
• Nutritional support: Ensure adequate calories, calcium, and vitamin D.
• Monitor: Growth, electrolytes, bone health, and renal function.

✅ Model Answer:
• Growth failure: Malnutrition, electrolyte imbalance, rickets.
• Rickets/osteomalacia: Bone pain, deformities, fractures.
• Chronic kidney disease (CKD): If the underlying condition progresses (e.g., cystinosis).
• Dehydration: Salt wasting and polyuria.
• Electrolyte imbalances: Hypokalemia, hypophosphatemia, metabolic acidosis.
• Nephrolithiasis: Due to hypercalciuria (rare).
• Psychosocial: Impact of chronic illness and dietary restrictions.

✅ Model Answer:
• Prognosis:
- Depends on the underlying cause:
- Cystinosis: Progressive CKD; ESKD by adolescence without treatment; cysteamine slows progression.
- Galactosemia: Good prognosis with dietary restriction.
- Drug-induced: Reversible if drug is withdrawn early.
- Idiopathic: Variable; may improve with age.
- Growth: Can improve with electrolyte replacement.
- Life expectancy: Normal for non-cystinosis causes; reduced for cystinosis if untreated.
• Long-term follow-up:
- Monitor growth, electrolytes, bone health.
- Monitor renal function.
- Genetic counseling.
- Multidisciplinary care.

✅ Model Answer:
• Cystinosis: An autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene (cystinosin).
• Pathophysiology: Defective transport of cystine out of lysosomes → accumulation of cystine crystals in tissues (kidneys, eyes, thyroid, brain).
• Renal involvement: Cystine accumulation in proximal tubular cells → Fanconi syndrome (most common cause in children).
• Diagnosis: Elevated WBC cystine level (confirmatory).
• Treatment: Cysteamine (depletes cystine) – slows progression of CKD and improves growth.
• Complications: Progressive CKD, ESKD by adolescence, corneal crystals, hypothyroidism, diabetes mellitus.
• Prognosis: Improved with early cysteamine treatment; renal transplantation is an option.