Fanconi Syndrome

Fanconi syndrome is generalised proximal tubular dysfunction with impaired reabsorption of phosphate, glucose, amino acids, bicarbonate, uric acid, potassium and low molecular weight proteins.

• Inherited: cystinosis (commonest in children), Dent disease, Lowe syndrome (oculocerebrorenal), tyrosinaemia type I, galactosaemia, hereditary fructose intolerance, Wilson disease, glycogen storage disease type XI (Fanconi-Bickel), mitochondrial disease, idiopathic.
• Acquired: drugs (tenofovir disoproxil, ifosfamide, cisplatin, aminoglycosides, valproate, expired tetracycline, deferasirox, aristolochic acid, ifosfamide, lithium), monoclonal light chains (myeloma, Sjögren), heavy metals (cadmium, lead, mercury), Sjögren syndrome, amyloidosis, vitamin D deficiency, nephrotic syndrome.
• Complications: rickets or osteomalacia, growth retardation, proximal renal tubular acidosis, polyuria, dehydration, hypokalaemia, progression to CKD.

• Children: failure to thrive, polyuria, polydipsia, vomiting, dehydration, rickets, growth failure, photophobia (cystinosis).
• Adults: bone pain, osteomalacia, proximal myopathy, muscle weakness, fatigue, polyuria.
• Features of the underlying cause: corneal crystals, hypothyroidism (cystinosis), cataracts and intellectual disability (Lowe), liver disease (tyrosinaemia, Wilson), myeloma.
• Fractures from osteomalacia.

• Normoglycaemic glycosuria, generalised aminoaciduria, phosphaturia (low serum phosphate, TmP/GFR reduced), hypouricaemia, hypokalaemia, proximal RTA (non-anion gap acidosis with urine pH under 5.5 once serum bicarbonate is low), low molecular weight proteinuria (beta-2 microglobulin, retinol-binding protein).
• Low serum phosphate, calcium, high alkaline phosphatase, low 1,25-dihydroxyvitamin D (variable).
• Search for cause: leukocyte cystine, slit-lamp eye examination (cystine crystals), urine organic acids and succinylacetone, serum free light chains and immunofixation, copper and ceruloplasmin, drug and toxin review, genetic testing.
• Bone radiographs (rickets, Looser zones), renal ultrasound for nephrocalcinosis.
• Renal biopsy if monoclonal gammopathy or unexplained.

• Treat or remove the cause: stop tenofovir disoproxil (switch to alafenamide), ifosfamide, cisplatin; chemotherapy for myeloma; dietary therapy for tyrosinaemia or galactosaemia/fructose intolerance; copper chelation for Wilson disease; nitisinone for tyrosinaemia type I (1 mg/kg/day).
• Replace losses:
  • Fluids and electrolytes: sodium chloride, potassium citrate/bicarbonate 2 to 10 mmol/kg/day to correct acidosis and hypokalaemia.
  • Phosphate 30 to 60 mg/kg/day elemental in 4 to 5 divided doses (with caution to avoid hyperparathyroidism and diarrhoea) and calcitriol 20 to 50 ng/kg/day or alfacalcidol.
  • Vitamin D (ergocalciferol or cholecalciferol 1000 to 4000 IU/day or more), calcium supplements.
  • Alkali: sodium bicarbonate or citrate solutions (Shohl's) 5 to 15 mmol/kg/day in proximal RTA.
• Indomethacin or thiazides to reduce polyuria and electrolyte losses (with caution).
• Cystinosis: cysteamine 1.3 g/m2/day (maximum) in divided doses (delayed-release 1.3 g/m2 twice daily), topical cysteamine eye drops hourly while awake for corneal crystals; early treatment preserves renal function. Renal transplantation for ESKD, thyroid hormone replacement.
• Dent disease and others: supportive therapy, thiazide for hypercalciuria.
• Growth hormone in persistent growth failure after metabolic correction.
• Monitor electrolytes, phosphate, bone profile, growth and renal function every 3 to 6 months.