Fanconi Syndrome
Summary
Fanconi syndrome is a generalised dysfunction of the proximal convoluted tubule (PCT) of the kidney, leading to impaired reabsorption of multiple substances normally reclaimed from the filtrate. This results in urinary wasting of glucose, amino acids, phosphate, bicarbonate, potassium, uric acid, and sodium. Clinically, patients develop glucosuria (despite normal blood glucose), phosphaturia causing hypophosphataemic rickets/osteomalacia, aminoaciduria, and Type 2 (proximal) renal tubular acidosis. Causes include inherited disorders (cystinosis, Wilson's disease) and acquired causes (drugs like tenofovir, heavy metals, myeloma). Treatment focuses on replacing lost electrolytes and treating the underlying cause.
Key Facts
- Pathology: Generalised proximal tubule dysfunction
- Losses: Glucose, Amino acids, Phosphate, Bicarbonate, Potassium, Uric acid
- Causes: Cystinosis (children), Myeloma, Tenofovir, Heavy metals
- Consequences: Rickets/Osteomalacia (phosphate loss), Type 2 RTA (bicarb loss)
- Key Feature: Glucosuria with NORMAL blood glucose
- Treatment: Replace losses; Treat underlying cause
Clinical Pearls
"Glucosuria Without Hyperglycaemia": The classic clue - glucose in the urine but normal blood sugar. This is renal glycosuria due to PCT dysfunction.
"Think Cystinosis in Children": In a child with Fanconi syndrome, cystinosis is the most common inherited cause. Look for corneal cystine crystals.
"Type 2 RTA = Proximal": Bicarbonate is lost in the urine. The acidosis is usually mild because the distal tubule can still acidify urine.
"Tenofovir Is a Common Culprit": Drug-induced Fanconi syndrome is increasingly recognised, especially with tenofovir (HIV treatment).
Incidence
- Rare (inherited forms)
- Acquired forms increasingly recognised
Age
- Inherited: Presents in infancy/childhood
- Acquired: Any age
Causes
| Category | Examples |
|---|---|
| Inherited | Cystinosis (most common in children), Wilson's disease, Galactosaemia, Hereditary fructose intolerance, Glycogen storage diseases, Lowe syndrome |
| Drugs | Tenofovir, Ifosfamide, Cisplatin, Aminoglycosides, Valproate, Expired tetracyclines |
| Toxins | Lead, Mercury, Cadmium |
| Acquired diseases | Myeloma, Amyloidosis, Sjögren's syndrome |
| Other | Renal transplant, Vitamin D deficiency |
Proximal Tubule Function
- Reabsorbs ~65% of filtered sodium, water, bicarbonate
- Reabsorbs 100% of filtered glucose and amino acids
- Reabsorbs ~80% of filtered phosphate
Mechanism in Fanconi Syndrome
- Global PCT dysfunction → Failure of multiple reabsorption pathways
- May affect sodium-dependent cotransporters (SGLT2, NaPi-IIa, etc.)
- Mechanism varies by cause (e.g., cystine accumulation in cystinosis)
Consequences
| Lost Substance | Clinical Effect |
|---|---|
| Glucose | Glucosuria (but normoglycaemia) |
| Amino acids | Aminoaciduria |
| Phosphate | Hypophosphataemia → Rickets/Osteomalacia |
| Bicarbonate | Type 2 RTA (metabolic acidosis) |
| Potassium | Hypokalaemia |
| Uric acid | Hypouricaemia |
| Sodium/Water | Polyuria, dehydration |
Children (Inherited Causes)
| Feature | Notes |
|---|---|
| Failure to thrive | Poor growth |
| Rickets | Bow legs, widened wrists, delayed walking |
| Polyuria/polydipsia | Sodium/water wasting |
| Weakness | Hypokalaemia |
| Metabolic acidosis | Type 2 RTA |
Adults (Acquired Causes)
| Feature | Notes |
|---|---|
| Bone pain | Osteomalacia, fractures |
| Muscle weakness | Hypokalaemia, hypophosphataemia |
| Polyuria | |
| Fatigue |
Specific Causes
General
- Growth failure (children)
- Signs of rickets (children)
Musculoskeletal
- Rickets: Widened wrists, rachitic rosary, bow legs
- Osteomalacia: Proximal myopathy
Eyes (Cystinosis)
- Slit-lamp: Corneal cystine crystals
Urine Tests
| Test | Finding |
|---|---|
| Urine glucose | Positive (with normal blood glucose) |
| Urine amino acids | Generalised aminoaciduria |
| Urine phosphate (TmP/GFR) | Low (phosphate wasting) |
| Urine pH | May be <5.5 (despite systemic acidosis) |
| Urine beta-2 microglobulin | Elevated (tubular proteinuria) |
Blood Tests
| Test | Finding |
|---|---|
| Glucose | Normal |
| Phosphate | Low |
| Bicarbonate | Low (metabolic acidosis) |
| Potassium | Low |
| Uric acid | Low |
| Calcium | Usually normal |
| ALP | Elevated (rickets/osteomalacia) |
Additional
- Cystine levels (if cystinosis suspected)
- Ceruloplasmin, copper (Wilson's)
- Serum protein electrophoresis (myeloma)
- Drug history (tenofovir, ifosfamide)
Treatment Approach
┌──────────────────────────────────────────────────────────┐
│ FANCONI SYNDROME MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ TREAT UNDERLYING CAUSE: │
│ • Stop causative drug (tenofovir, ifosfamide) │
│ • Treat myeloma, Wilson's, cystinosis │
│ • Cysteamine for cystinosis │
│ │
│ REPLACEMENT THERAPY: │
│ • Phosphate supplements (Phosphate Sandoz) │
│ • Bicarbonate (Sodium bicarbonate tablets) │
│ • Potassium (if hypokalaemic) │
│ • Vitamin D (Alfacalcidol/Cholecalciferol) │
│ • Fluid replacement (if polyuric) │
│ │
│ MONITORING: │
│ • Regular electrolytes (PO4, K, HCO3) │
│ • Bone health (ALP, DEXA, X-rays) │
│ • Growth (children) │
│ • Renal function │
│ │
│ MDT INVOLVEMENT: │
│ • Nephrology │
│ • Metabolic medicine │
│ • Paediatrics/Endocrinology │
│ │
└──────────────────────────────────────────────────────────┘
Of Disease
- Rickets/Osteomalacia (bone deformity, fractures)
- Growth failure
- Hypokalaemia (arrhythmias, weakness)
- Chronic kidney disease (progressive)
Of Underlying Cause
- Cystinosis: Renal failure, hypothyroidism, diabetes
- Wilson's: Liver failure, neurological disease
With Treatment
- Variable; depends on underlying cause
- Drug-induced: Often reversible if drug stopped
- Cystinosis: Progressive without cysteamine; improves with treatment
Without Treatment
- Progressive bone disease
- Growth failure
- CKD progression
Key Guidelines
- Rare Renal Disease Guidelines
- Cystinosis Network Guidelines
Key Evidence
Cysteamine
- Delays progression to ESRD in cystinosis
Tenofovir
- Well-documented cause; reversible on cessation
What is Fanconi Syndrome?
Fanconi syndrome is a kidney problem where part of the kidney (called the proximal tubule) doesn't work properly. Normally, this part of the kidney saves useful things like glucose, amino acids, and minerals from being lost in the urine. In Fanconi syndrome, these are lost, causing problems.
What Causes It?
- Inherited conditions (like cystinosis)
- Certain medications (like tenofovir)
- Other diseases (like myeloma)
What Are the Symptoms?
- Weak bones (rickets in children, soft bones in adults)
- Tiredness and muscle weakness
- Needing to urinate a lot
- Poor growth in children
How is it Treated?
- Treating the underlying cause (stopping a drug, treating the disease)
- Replacing what's being lost (phosphate, bicarbonate, potassium, vitamin D)
- Regular monitoring
Primary Guidelines
- Renal Association. Clinical Practice Guidelines.
Key Studies
- Kleta R, Bhargava P. Nephropathic cystinosis. Nat Rev Nephrol. 2010;6(1):21-30. PMID: 19935735