Updated: 11/6/2018

Fanconi Syndrome

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  • A 10-year-old girl with a past medical history of epilepsy presents to the emergency room after sustaining a fall on the playground. She was fatigued and confused after the event and complained of pain in her wrist. On review of systems, she endorsed polyuria and polydipsia. Relevant medications included valproic acid, started 6 months ago, for her epilepsy. On physical exam, her right wrist was erythematous, swollen, and tender.  Laboratory evaluation revealed hypokalemia, hypocalcemia, hypophosphatemia, and a mild metabolic acidosis.
Introduction
  • Clinical definition
    • a type of renal tubular acidosis (type 2) in the proximal convoluted tubules (PCT)
  • Epidemiology
    • incidence
      • hereditary forms occur in 1:40,000
    • demographics
      • hereditary forms affect Caucasian children
  • Etiology
    • hereditary conditions
      • cystinosis
        • most common genetic cause
      • Wilson disease
      • tyrosinemia
      • galactosemia
    • multiple myeloma
    • drugs
      • cisplatin
      • tenofovir
      • valproic acid
      • expired tetracyclines
      • ifosfamide
    • heavy metal poisonings
  • Pathogenesis
    • defect in PCT causes problems in reabsorption of almost all amino acids, glucose, bicarbonate, phosphate, and potassium
      • this causes all of the above to be excreted in the urine
      • excretion of bicarbonate causes a metabolic acidosis
    • defect is due to
      • direct injury to PCT
      • in genetic cases there is often a defective enzyme in nutrient metabolism that causes damage to the PCT
      • light chains form crystals in PCT, causing damage
  • Associated conditions
    • osteomalacia/rickets
      • chronic phosphate and insufficient synthesis of vitamin D
    • hypokalemia
      • due to ↓ early Na+ reabsorption leading to ↑ K+ exchange
  • Prognosis
    • depends on etiology of Fanconi syndrome
    • prognostic variable
      • negative
        • hereditary diseases
Presentation
  • Symptoms
    • primary symptoms
      • renal disease
        • polyuria
        • polydipsia
      • bone disease
        • bone pain in the backs and hips
        • pathologic fractures
      • constitutional
        • myalgias
        • weight loss
        • fatigue
      • hereditary abnormalities
        • failure to thrive
        • developmental delay
  • Physical exam
    • signs of rickets
      • bowed legs
      • scoliosis
      • teeth abnormalities
Studies
  • Labs
    • electrolyte panel
      • hyponatremia
      • hypokalemia
      • hypocalcemia
      • hypophosphatemia
    • ↑ serum creatinine
    • metabolic acidosis
  • Urine studies 
    • aminoaciduria
    • glycosuria
    • phosphaturia
    • urine pH < 5.5
      • defect in bicarbonate reabsorption leads to increased excretion of bicarbonate in urine
      • urine is then acidified by the intercalated cells in collecting tubule
  • Diagnostic criteria
    • no specific criteria, but these findings could suggest Fanconi syndrome
      • increased excretion of amino acids, phosphates, and bicarbonate in the urine
      • metabolic acidosis
Differential
  • Distal renal tubular acidosis (type 1)
    • urine pH > 5.5
  • Hyperkalemic renal tubular acidosis (type 4)
    • hyperkalemia and urine pH < 5.5
Treatment
  • Conservative
    • supportive care with fluid and electrolyte repletion
      • indications
        • if any metabolic derangements are found
        • especially if hypokalemia or hypophosphatemia are found
  • Medical
    • vitamin D (active form, cholecalciferol. or ergocalciferol)
      • indications
        • if osteomalacia is present
    • bicarbonate
      • indications
        • metabolic acidosis
Complications
  • Bone disease (osteomalacia, osteopenia, and osteoporosis)
  • Renal insufficiency

References

 

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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