Diferencia entre revisiones de «Fanconi syndrome»

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Fanconi syndrome is a generalized dysfunction of the '''proximal renal tubule''' resulting in impaired reabsorption of glucose, amino acids, phosphate, bicarbonate, uric acid, potassium, sodium, and low-molecular-weight proteins. It produces a '''type 2 (proximal) [[Renal tubular acidosis|renal tubular acidosis]]''' and may cause life-threatening [[Hypokalemia|hypokalemia]], [[Metabolic acidosis|metabolic acidosis]], dehydration, and bone disease.<ref name="StatPearls">Fanconi Syndrome. ''StatPearls''. 2025. PMID: 30521243</ref> It is '''not''' the same as [[Fanconi anemia]], which is a separate inherited bone marrow failure syndrome.
==Background==
==Background==
*Fanconi syndrome is a generalized dysfunction of the proximal renal tubule resulting in impaired reabsorption of glucose, amino acids, phosphate, bicarbonate, uric acid, potassium, sodium, and low-molecular-weight proteins.
*It produces a type 2 (proximal) [[Renal tubular acidosis|renal tubular acidosis]] and may cause life-threatening [[Hypokalemia|hypokalemia]], [[Metabolic acidosis|metabolic acidosis]], dehydration, and bone disease.<ref name="StatPearls">Fanconi Syndrome. ''StatPearls''. 2025. PMID: 30521243</ref> It is not the same as [[Fanconi anemia]], which is a separate inherited bone marrow failure syndrome.
*The proximal convoluted tubule (PCT) normally reabsorbs ~65% of filtered sodium, water, bicarbonate, glucose, amino acids, phosphate, and uric acid
*The proximal convoluted tubule (PCT) normally reabsorbs ~65% of filtered sodium, water, bicarbonate, glucose, amino acids, phosphate, and uric acid
*In Fanconi syndrome, '''global PCT dysfunction''' causes urinary wasting of all these solutes simultaneously<ref name="StatPearls"/>
*In Fanconi syndrome, '''global PCT dysfunction''' causes urinary wasting of all these solutes simultaneously<ref name="StatPearls"/>
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===Inherited causes===
===Inherited causes===
*'''[[Cystinosis]]''' — most common inherited cause (presents in infancy, 6-18 months)
* [[Cystinosis]] — most common inherited cause (presents in infancy, 6-18 months)
*[[Wilson disease]]
*[[Wilson disease]]
*Hereditary fructose intolerance
*Hereditary fructose intolerance
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===Acquired causes (most EM-relevant)===
===Acquired causes (most EM-relevant)===
*'''Medications''' (most common acquired cause):<ref name="StatPearls"/><ref name="Medscape">Fanconi Syndrome. ''Medscape''. 2024.</ref>
* Medications (most common acquired cause):<ref name="StatPearls"/><ref name="Medscape">Fanconi Syndrome. ''Medscape''. 2024.</ref>
**'''Tenofovir''' (TDF; especially in HIV patients with pre-existing renal impairment) — most commonly encountered drug cause today
** Tenofovir (TDF; especially in HIV patients with pre-existing renal impairment) — most commonly encountered drug cause today
**'''Ifosfamide''' — particularly in children after cumulative doses
** Ifosfamide — particularly in children after cumulative doses
**'''Cisplatin, carboplatin'''
** Cisplatin, carboplatin
**'''Valproic acid''' — especially with polytherapy and prolonged use
** Valproic acid — especially with polytherapy and prolonged use
**'''Expired tetracyclines''' (degradation products are directly nephrotoxic)
** Expired tetracyclines (degradation products are directly nephrotoxic)
**Adefovir, cidofovir, didanosine
**Adefovir, cidofovir, didanosine
**Aminoglycosides (gentamicin)
**Aminoglycosides (gentamicin)
**Lenalidomide, streptozocin
**Lenalidomide, streptozocin
*'''Heavy metals:'''
* Heavy metals:
**[[Lead poisoning]] (most common heavy metal cause in children)
**[[Lead poisoning]] (most common heavy metal cause in children)
**Cadmium, mercury, platinum, uranium
**Cadmium, mercury, platinum, uranium
*'''Paraproteinemia:'''
* Paraproteinemia:
**[[Multiple myeloma]] (light chain proximal tubulopathy)
**[[Multiple myeloma]] (light chain proximal tubulopathy)
**AL amyloidosis
**AL amyloidosis
*'''Other:'''
* Other:
**Renal transplant
**Renal transplant
**Toluene exposure (glue sniffing)
**Toluene exposure (glue sniffing)
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===Acute/ED presentation===
===Acute/ED presentation===
*'''[[Hypokalemia]]''' — may be '''severe and life-threatening'''; case reports of [[Cardiac arrest|cardiac arrest]] from Fanconi-related hypokalemia<ref name="Cardiac">A 57-Year-Old Female Presenting With Cardiopulmonary Arrest Secondary to Severe Hypokalemia From a Fanconi-Like Syndrome. ''Cureus''. 2024;16(3):e55705. doi:10.7759/cureus.55705</ref>
* [[Hypokalemia]] — may be '''severe and life-threatening'''; case reports of [[Cardiac arrest|cardiac arrest]] from Fanconi-related hypokalemia<ref name="Cardiac">A 57-Year-Old Female Presenting With Cardiopulmonary Arrest Secondary to Severe Hypokalemia From a Fanconi-Like Syndrome. ''Cureus''. 2024;16(3):e55705. doi:10.7759/cureus.55705</ref>
*'''[[Metabolic acidosis]]''' — non-anion gap (hyperchloremic) from '''proximal (type 2) [[Renal tubular acidosis|RTA]]''' (bicarbonate wasting)
* [[Metabolic acidosis]] — non-anion gap (hyperchloremic) from proximal (type 2) [[Renal tubular acidosis|RTA]] (bicarbonate wasting)
*'''Polyuria, polydipsia''' (from impaired water/sodium reabsorption)
* Polyuria, polydipsia (from impaired water/sodium reabsorption)
*'''Dehydration''', volume depletion
* Dehydration, volume depletion
*'''Muscle weakness''' (from hypokalemia and hypophosphatemia)
* Muscle weakness (from hypokalemia and hypophosphatemia)
*Nausea, vomiting
*Nausea, vomiting
*Fatigue, malaise
*Fatigue, malaise


===Chronic/subacute presentation===
===Chronic/subacute presentation===
*'''Children:'''
* Children:
**Failure to thrive, growth retardation
**Failure to thrive, growth retardation
**'''Rickets''' (hypophosphatemic; from phosphate wasting + impaired 1,25-dihydroxyvitamin D synthesis in PCT)
** Rickets (hypophosphatemic; from phosphate wasting + impaired 1,25-dihydroxyvitamin D synthesis in PCT)
**Bone pain, pathologic fractures
**Bone pain, pathologic fractures
**Polyuria, polydipsia
**Polyuria, polydipsia
*'''Adults:'''
* Adults:
**'''Osteomalacia''' (bone pain, pathologic fractures, proximal muscle weakness)
** Osteomalacia (bone pain, pathologic fractures, proximal muscle weakness)
**Chronic fatigue, muscle weakness
**Chronic fatigue, muscle weakness
**Kidney stones (hypercalciuria in some forms)
**Kidney stones (hypercalciuria in some forms)
**Progressive chronic kidney disease
**Progressive chronic kidney disease
*'''Cystinosis-specific:''' corneal cystine crystals, hepatomegaly, hypothyroidism, retinal depigmentation, growth failure
* Cystinosis-specific: corneal cystine crystals, hepatomegaly, hypothyroidism, retinal depigmentation, growth failure


===Key laboratory pattern ("the Fanconi fingerprint")===
===Key laboratory pattern ("the Fanconi fingerprint")===
*'''Glycosuria with NORMAL serum glucose''' (not diabetes — inappropriately low renal glucose threshold)
* Glycosuria with NORMAL serum glucose (not diabetes — inappropriately low renal glucose threshold)
*'''Generalized aminoaciduria'''
* Generalized aminoaciduria
*'''Phosphaturia''' with hypophosphatemia
* Phosphaturia with hypophosphatemia
*'''Bicarbonaturia''' with non-anion gap metabolic acidosis (proximal RTA)
* Bicarbonaturia with non-anion gap metabolic acidosis (proximal RTA)
*'''Hypokalemia''' (renal potassium wasting)
* Hypokalemia (renal potassium wasting)
*'''Hypouricemia''' (uric acid wasting)
* Hypouricemia (uric acid wasting)
*'''Low-molecular-weight proteinuria''' (β₂-microglobulin, retinol-binding protein)
* Low-molecular-weight proteinuria (β₂-microglobulin, retinol-binding protein)


==Differential diagnosis==
==Differential diagnosis==
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*Renal glycosuria (isolated SGLT2 mutation)
*Renal glycosuria (isolated SGLT2 mutation)
*Pregnancy
*Pregnancy
{{Renal tubular disorders DDX}}
{{Hypokalemia DDX}}
{{Acid-base disorders DDX}}


==Evaluation==
==Evaluation==
===Workup===
===Workup===
*'''BMP:''' hypokalemia, hypophosphatemia, low bicarbonate (non-anion gap metabolic acidosis), low uric acid; BUN/creatinine for renal function
* BMP: hypokalemia, hypophosphatemia, low bicarbonate (non-anion gap metabolic acidosis), low uric acid; BUN/creatinine for renal function
*'''ABG/VBG:''' non-anion gap metabolic acidosis (hyperchloremic); urine pH may be <5.5 (unlike distal RTA) if serum bicarbonate is below the reabsorptive threshold
* ABG/VBG: non-anion gap metabolic acidosis (hyperchloremic); urine pH may be <5.5 (unlike distal RTA) if serum bicarbonate is below the reabsorptive threshold
*'''Urinalysis:'''
* Urinalysis:
**'''Glucosuria''' (with normal serum glucose — the hallmark clue)
** Glucosuria (with normal serum glucose — the hallmark clue)
**Proteinuria (low-molecular-weight)
**Proteinuria (low-molecular-weight)
*'''Urine electrolytes:''' elevated urine potassium (transtubular potassium gradient >7 suggests renal K⁺ wasting)
* Urine electrolytes: elevated urine potassium (transtubular potassium gradient >7 suggests renal K⁺ wasting)
*'''Urine amino acids:''' generalized aminoaciduria (elevated excretion of virtually all amino acids)
* Urine amino acids: generalized aminoaciduria (elevated excretion of virtually all amino acids)
*'''Fractional excretion of phosphate (FePO₄):''' elevated (>5%)
* Fractional excretion of phosphate (FePO₄): elevated (>5%)
*'''Fractional excretion of uric acid:''' elevated (>10%)
* Fractional excretion of uric acid: elevated (>10%)
*'''Serum phosphate, uric acid, calcium, magnesium, vitamin D (25-OH and 1,25-OH), PTH'''
* Serum phosphate, uric acid, calcium, magnesium, vitamin D (25-OH and 1,25-OH), PTH
*'''Urine β₂-microglobulin''' — marker of proximal tubular injury<ref name="StatPearls"/>
* Urine β₂-microglobulin — marker of proximal tubular injury<ref name="StatPearls"/>
*'''ECG:''' assess for hypokalemia-related changes (U waves, flattened T waves, ST depression, prolonged QT, arrhythmias)
* ECG: assess for hypokalemia-related changes (U waves, flattened T waves, ST depression, prolonged QT, arrhythmias)
*'''Additional workup directed at underlying cause:'''
* Additional workup directed at underlying cause:
**Medication review (tenofovir, valproic acid, ifosfamide, expired tetracyclines)
**Medication review (tenofovir, valproic acid, ifosfamide, expired tetracyclines)
**Serum and urine protein electrophoresis, free light chains (multiple myeloma)
**Serum and urine protein electrophoresis, free light chains (multiple myeloma)
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===Diagnosis===
===Diagnosis===
*Clinical diagnosis based on the '''constellation''' of: glycosuria with normoglycemia + generalized aminoaciduria + phosphaturia + bicarbonaturia + hypokalemia<ref name="MerckManual">Fanconi Syndrome. ''Merck Manual Professional Edition''. 2024.</ref>
*Clinical diagnosis based on the constellation of: glycosuria with normoglycemia + generalized aminoaciduria + phosphaturia + bicarbonaturia + hypokalemia<ref name="MerckManual">Fanconi Syndrome. ''Merck Manual Professional Edition''. 2024.</ref>
*No single test is diagnostic; the '''pattern''' of proximal tubular losses is key
*No single test is diagnostic; the pattern of proximal tubular losses is key
*Once Fanconi syndrome is identified, the underlying cause must be sought
*Once Fanconi syndrome is identified, the underlying cause must be sought


==Management==
==Management==
===Emergency management (acute presentations)===
===Emergency management (acute presentations)===
*'''Hypokalemia:'''
* Hypokalemia:
**Aggressive IV and PO potassium repletion; may be '''profoundly refractory''' due to ongoing renal losses<ref name="Cardiac"/>
**Aggressive IV and PO potassium repletion; may be profoundly refractory due to ongoing renal losses<ref name="Cardiac"/>
**Continuous cardiac monitoring if K⁺ <3.0 mEq/L or symptomatic
**Continuous cardiac monitoring if K⁺ <3.0 mEq/L or symptomatic
**Target serum K⁺ >4.0 mEq/L
**Target serum K⁺ >4.0 mEq/L
**Consider '''amiloride''' or '''spironolactone''' to reduce renal potassium wasting
**Consider amiloride or spironolactone to reduce renal potassium wasting
*'''Metabolic acidosis:'''
* Metabolic acidosis:
**Oral or IV '''sodium bicarbonate''' or '''sodium citrate/potassium citrate''' (Bicitra, Polycitra)
**Oral or IV sodium bicarbonate or sodium citrate/potassium citrate (Bicitra, Polycitra)
**Large doses may be required (10-15 mEq/kg/day in children) because bicarbonate is lost in the urine
**Large doses may be required (10-15 mEq/kg/day in children) because bicarbonate is lost in the urine
**Caution: bicarbonate repletion may worsen hypokalemia (drives K⁺ intracellularly and increases distal delivery); replete potassium FIRST or concurrently
**Caution: bicarbonate repletion may worsen hypokalemia (drives K⁺ intracellularly and increases distal delivery); replete potassium FIRST or concurrently
*'''Dehydration:''' IV fluid resuscitation; may need large volumes due to polyuria
* Dehydration: IV fluid resuscitation; may need large volumes due to polyuria
*'''Hypophosphatemia:'''
* Hypophosphatemia:
**Oral phosphate supplementation (Neutra-Phos, K-Phos)
**Oral phosphate supplementation (Neutra-Phos, K-Phos)
**IV phosphate if severe (<1 mg/dL) or symptomatic
**IV phosphate if severe (<1 mg/dL) or symptomatic
*'''Hypoglycemia:''' IV dextrose if present (hereditary fructose intolerance may present with hypoglycemia)
* Hypoglycemia: IV dextrose if present (hereditary fructose intolerance may present with hypoglycemia)


===Identify and treat the underlying cause===
===Identify and treat the underlying cause===
*'''Drug-induced:''' '''discontinue the offending agent''' — this is the most important intervention for acquired Fanconi syndrome<ref name="StatPearls"/>
* Drug-induced: '''discontinue the offending agent''' — this is the most important intervention for acquired Fanconi syndrome<ref name="StatPearls"/>
**Tenofovir: switch to tenofovir alafenamide (TAF) or alternative antiretroviral
**Tenofovir: switch to tenofovir alafenamide (TAF) or alternative antiretroviral
**Valproic acid: consider alternative antiepileptic
**Valproic acid: consider alternative antiepileptic
**Expired tetracyclines: discard
**Expired tetracyclines: discard
**Recovery after drug withdrawal may take '''weeks to months'''<ref name="Medscape"/>
**Recovery after drug withdrawal may take weeks to months<ref name="Medscape"/>
*'''Heavy metal poisoning:''' chelation therapy as appropriate (see [[Lead poisoning]])
* Heavy metal poisoning: chelation therapy as appropriate (see [[Lead poisoning]])
*'''Multiple myeloma/paraproteinemia:''' hematology/oncology referral for treatment of underlying disease
* Multiple myeloma/paraproteinemia: hematology/oncology referral for treatment of underlying disease
*'''Cystinosis:''' '''cysteamine''' (Cystagon) — reduces intracellular cystine accumulation; early initiation improves renal outcomes
* Cystinosis: cysteamine (Cystagon) — reduces intracellular cystine accumulation; early initiation improves renal outcomes


===Long-term supplementation===
===Long-term supplementation===
*'''Bicarbonate/citrate:''' oral sodium bicarbonate or potassium citrate for chronic metabolic acidosis
* Bicarbonate/citrate: oral sodium bicarbonate or potassium citrate for chronic metabolic acidosis
*'''Phosphate:''' oral phosphate supplements
* Phosphate: oral phosphate supplements
*'''Vitamin D:''' calcitriol (1,25-dihydroxyvitamin D) — PCT dysfunction impairs conversion of 25-OH to active form
* Vitamin D: calcitriol (1,25-dihydroxyvitamin D) — PCT dysfunction impairs conversion of 25-OH to active form
*'''Potassium:''' oral supplementation; potassium-sparing diuretics if refractory
* Potassium: oral supplementation; potassium-sparing diuretics if refractory
*Nephrology follow-up for ongoing management and monitoring of renal function
*Nephrology follow-up for ongoing management and monitoring of renal function


==Disposition==
==Disposition==
*'''Severe hypokalemia (K⁺ <2.5 mEq/L), symptomatic hypokalemia, or cardiac arrhythmias:''' admit to monitored setting; continuous telemetry; serial electrolytes<ref name="Cardiac"/>
* Severe hypokalemia (K⁺ <2.5 mEq/L), symptomatic hypokalemia, or cardiac arrhythmias: admit to monitored setting; continuous telemetry; serial electrolytes<ref name="Cardiac"/>
*'''Severe metabolic acidosis (pH <7.2):''' admit for IV bicarbonate and electrolyte management
* Severe metabolic acidosis (pH <7.2): admit for IV bicarbonate and electrolyte management
*'''Significant dehydration or hemodynamic instability:''' admit for IV resuscitation
* Significant dehydration or hemodynamic instability: admit for IV resuscitation
*'''New diagnosis of Fanconi syndrome:''' may require admission or urgent outpatient workup depending on severity; nephrology consultation
* New diagnosis of Fanconi syndrome: may require admission or urgent outpatient workup depending on severity; nephrology consultation
*'''Stable, known Fanconi syndrome with mild electrolyte abnormalities:''' outpatient management with close nephrology follow-up, medication adjustment, and return precautions for weakness, palpitations, or syncope
* Stable, known Fanconi syndrome with mild electrolyte abnormalities: outpatient management with close nephrology follow-up, medication adjustment, and return precautions for weakness, palpitations, or syncope
*'''Medication-induced Fanconi:''' ensure offending drug is held and arrange nephrology and primary care follow-up for drug substitution and monitoring of recovery
* Medication-induced Fanconi: ensure offending drug is held and arrange nephrology and primary care follow-up for drug substitution and monitoring of recovery


==See Also==
==See Also==

Revisión actual - 09:36 22 mar 2026

Background

  • Fanconi syndrome is a generalized dysfunction of the proximal renal tubule resulting in impaired reabsorption of glucose, amino acids, phosphate, bicarbonate, uric acid, potassium, sodium, and low-molecular-weight proteins.
  • It produces a type 2 (proximal) renal tubular acidosis and may cause life-threatening hypokalemia, metabolic acidosis, dehydration, and bone disease.[1] It is not the same as Fanconi anemia, which is a separate inherited bone marrow failure syndrome.
  • The proximal convoluted tubule (PCT) normally reabsorbs ~65% of filtered sodium, water, bicarbonate, glucose, amino acids, phosphate, and uric acid
  • In Fanconi syndrome, global PCT dysfunction causes urinary wasting of all these solutes simultaneously[1]
  • Pathophysiology centers on mitochondrial dysfunction → ATP depletion → failure of Na⁺/K⁺-ATPase and energy-dependent transport systems[1]
  • Can be inherited or acquired; acquired forms are more relevant to the emergency physician

Inherited causes

  • Cystinosis — most common inherited cause (presents in infancy, 6-18 months)
  • Wilson disease
  • Hereditary fructose intolerance
  • Galactosemia
  • Glycogen storage diseases
  • Lowe syndrome (oculocerebrorenal syndrome)
  • Dent disease
  • Fanconi-Bickel syndrome
  • Tyrosinemia type 1
  • Mitochondrial cytopathies

Acquired causes (most EM-relevant)

  • Medications (most common acquired cause):[1][2]
    • Tenofovir (TDF; especially in HIV patients with pre-existing renal impairment) — most commonly encountered drug cause today
    • Ifosfamide — particularly in children after cumulative doses
    • Cisplatin, carboplatin
    • Valproic acid — especially with polytherapy and prolonged use
    • Expired tetracyclines (degradation products are directly nephrotoxic)
    • Adefovir, cidofovir, didanosine
    • Aminoglycosides (gentamicin)
    • Lenalidomide, streptozocin
  • Heavy metals:
    • Lead poisoning (most common heavy metal cause in children)
    • Cadmium, mercury, platinum, uranium
  • Paraproteinemia:
  • Other:
    • Renal transplant
    • Toluene exposure (glue sniffing)
    • Aristolochic acid (herbal medicines)
    • Paraquat poisoning

Clinical features

  • Presentation varies widely depending on the underlying cause, severity, and chronicity
  • May range from an incidental laboratory finding to life-threatening electrolyte emergency

Acute/ED presentation

  • Hypokalemia — may be severe and life-threatening; case reports of cardiac arrest from Fanconi-related hypokalemia[3]
  • Metabolic acidosis — non-anion gap (hyperchloremic) from proximal (type 2) RTA (bicarbonate wasting)
  • Polyuria, polydipsia (from impaired water/sodium reabsorption)
  • Dehydration, volume depletion
  • Muscle weakness (from hypokalemia and hypophosphatemia)
  • Nausea, vomiting
  • Fatigue, malaise

Chronic/subacute presentation

  • Children:
    • Failure to thrive, growth retardation
    • Rickets (hypophosphatemic; from phosphate wasting + impaired 1,25-dihydroxyvitamin D synthesis in PCT)
    • Bone pain, pathologic fractures
    • Polyuria, polydipsia
  • Adults:
    • Osteomalacia (bone pain, pathologic fractures, proximal muscle weakness)
    • Chronic fatigue, muscle weakness
    • Kidney stones (hypercalciuria in some forms)
    • Progressive chronic kidney disease
  • Cystinosis-specific: corneal cystine crystals, hepatomegaly, hypothyroidism, retinal depigmentation, growth failure

Key laboratory pattern ("the Fanconi fingerprint")

  • Glycosuria with NORMAL serum glucose (not diabetes — inappropriately low renal glucose threshold)
  • Generalized aminoaciduria
  • Phosphaturia with hypophosphatemia
  • Bicarbonaturia with non-anion gap metabolic acidosis (proximal RTA)
  • Hypokalemia (renal potassium wasting)
  • Hypouricemia (uric acid wasting)
  • Low-molecular-weight proteinuria (β₂-microglobulin, retinol-binding protein)

Differential diagnosis

Proximal Renal tubular acidosis

  • Isolated proximal RTA (type 2) without full Fanconi features
  • Renal tubular acidosis (type 1)
  • Type 4 RTA (hypoaldosteronism)

Other causes of non-anion gap metabolic acidosis

  • Diarrhea
  • Ureteral diversion
  • Carbonic anhydrase inhibitors (acetazolamide)

Other causes of unexplained hypokalemia

Other causes of glycosuria with normal glucose

  • Renal glycosuria (isolated SGLT2 mutation)
  • Pregnancy


Renal tubular disorders

  • Salt-wasting tubulopathies
    • Gitelman syndrome — distal convoluted tubule (NCC defect); hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis
    • Bartter syndrome — thick ascending limb (NKCC2/ROMK/ClC-Kb defect); hypokalemia, hypercalciuria, metabolic alkalosis
    • Liddle syndrome — collecting duct (ENaC gain-of-function); hypokalemia, hypertension, metabolic alkalosis
  • Renal tubular acidosis
  • Inherited disorders of tubular transport
    • Cystinuria — proximal tubule amino acid transport defect; recurrent cystine stones
    • Fanconi syndrome — proximal tubule generalized dysfunction; glucosuria, aminoaciduria, phosphaturia
    • Nephrogenic diabetes insipidus — collecting duct (aquaporin/V2R defect); polyuria, hypernatremia
    • Dent disease — proximal tubule (ClC-5 defect); low molecular weight proteinuria, nephrocalcinosis
  • Acquired tubulopathies

Hypokalemia


Acid-base disorders

Evaluation

Workup

  • BMP: hypokalemia, hypophosphatemia, low bicarbonate (non-anion gap metabolic acidosis), low uric acid; BUN/creatinine for renal function
  • ABG/VBG: non-anion gap metabolic acidosis (hyperchloremic); urine pH may be <5.5 (unlike distal RTA) if serum bicarbonate is below the reabsorptive threshold
  • Urinalysis:
    • Glucosuria (with normal serum glucose — the hallmark clue)
    • Proteinuria (low-molecular-weight)
  • Urine electrolytes: elevated urine potassium (transtubular potassium gradient >7 suggests renal K⁺ wasting)
  • Urine amino acids: generalized aminoaciduria (elevated excretion of virtually all amino acids)
  • Fractional excretion of phosphate (FePO₄): elevated (>5%)
  • Fractional excretion of uric acid: elevated (>10%)
  • Serum phosphate, uric acid, calcium, magnesium, vitamin D (25-OH and 1,25-OH), PTH
  • Urine β₂-microglobulin — marker of proximal tubular injury[1]
  • ECG: assess for hypokalemia-related changes (U waves, flattened T waves, ST depression, prolonged QT, arrhythmias)
  • Additional workup directed at underlying cause:
    • Medication review (tenofovir, valproic acid, ifosfamide, expired tetracyclines)
    • Serum and urine protein electrophoresis, free light chains (multiple myeloma)
    • Serum copper, ceruloplasmin (Wilson disease)
    • Lead level
    • White blood cell cystine level (cystinosis)
    • Slit-lamp examination (cystine corneal crystals)

Diagnosis

  • Clinical diagnosis based on the constellation of: glycosuria with normoglycemia + generalized aminoaciduria + phosphaturia + bicarbonaturia + hypokalemia[4]
  • No single test is diagnostic; the pattern of proximal tubular losses is key
  • Once Fanconi syndrome is identified, the underlying cause must be sought

Management

Emergency management (acute presentations)

  • Hypokalemia:
    • Aggressive IV and PO potassium repletion; may be profoundly refractory due to ongoing renal losses[3]
    • Continuous cardiac monitoring if K⁺ <3.0 mEq/L or symptomatic
    • Target serum K⁺ >4.0 mEq/L
    • Consider amiloride or spironolactone to reduce renal potassium wasting
  • Metabolic acidosis:
    • Oral or IV sodium bicarbonate or sodium citrate/potassium citrate (Bicitra, Polycitra)
    • Large doses may be required (10-15 mEq/kg/day in children) because bicarbonate is lost in the urine
    • Caution: bicarbonate repletion may worsen hypokalemia (drives K⁺ intracellularly and increases distal delivery); replete potassium FIRST or concurrently
  • Dehydration: IV fluid resuscitation; may need large volumes due to polyuria
  • Hypophosphatemia:
    • Oral phosphate supplementation (Neutra-Phos, K-Phos)
    • IV phosphate if severe (<1 mg/dL) or symptomatic
  • Hypoglycemia: IV dextrose if present (hereditary fructose intolerance may present with hypoglycemia)

Identify and treat the underlying cause

  • Drug-induced: discontinue the offending agent — this is the most important intervention for acquired Fanconi syndrome[1]
    • Tenofovir: switch to tenofovir alafenamide (TAF) or alternative antiretroviral
    • Valproic acid: consider alternative antiepileptic
    • Expired tetracyclines: discard
    • Recovery after drug withdrawal may take weeks to months[2]
  • Heavy metal poisoning: chelation therapy as appropriate (see Lead poisoning)
  • Multiple myeloma/paraproteinemia: hematology/oncology referral for treatment of underlying disease
  • Cystinosis: cysteamine (Cystagon) — reduces intracellular cystine accumulation; early initiation improves renal outcomes

Long-term supplementation

  • Bicarbonate/citrate: oral sodium bicarbonate or potassium citrate for chronic metabolic acidosis
  • Phosphate: oral phosphate supplements
  • Vitamin D: calcitriol (1,25-dihydroxyvitamin D) — PCT dysfunction impairs conversion of 25-OH to active form
  • Potassium: oral supplementation; potassium-sparing diuretics if refractory
  • Nephrology follow-up for ongoing management and monitoring of renal function

Disposition

  • Severe hypokalemia (K⁺ <2.5 mEq/L), symptomatic hypokalemia, or cardiac arrhythmias: admit to monitored setting; continuous telemetry; serial electrolytes[3]
  • Severe metabolic acidosis (pH <7.2): admit for IV bicarbonate and electrolyte management
  • Significant dehydration or hemodynamic instability: admit for IV resuscitation
  • New diagnosis of Fanconi syndrome: may require admission or urgent outpatient workup depending on severity; nephrology consultation
  • Stable, known Fanconi syndrome with mild electrolyte abnormalities: outpatient management with close nephrology follow-up, medication adjustment, and return precautions for weakness, palpitations, or syncope
  • Medication-induced Fanconi: ensure offending drug is held and arrange nephrology and primary care follow-up for drug substitution and monitoring of recovery

See Also

External Links

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Fanconi Syndrome. StatPearls. 2025. PMID: 30521243
  2. ↑ 2.0 2.1 Fanconi Syndrome. Medscape. 2024.
  3. ↑ 3.0 3.1 3.2 A 57-Year-Old Female Presenting With Cardiopulmonary Arrest Secondary to Severe Hypokalemia From a Fanconi-Like Syndrome. Cureus. 2024;16(3):e55705. doi:10.7759/cureus.55705
  4. ↑ Fanconi Syndrome. Merck Manual Professional Edition. 2024.
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