Case Presentation:
A 29‐year‐old African American man with no significant medical history presented with generalized fatigue, unintentional 25‐pound weight loss, and arthralgias. Physical examination was unremarkable. Blood work revealed creatinine 2.31 mg/dL, bicarbonate 25.2 mmol/L, glucose 94 mg/dL, and calcium 9 mg/dL. Baseline creatinine was not known. Liver function tests were normal except for an elevated alkaline phosphatase at 195 units/L. Urinalysis demonstrated urine pH 6, 100 mg/dL protein, 1000 mg/dL glucose, without cells or casts. He had been evaluated several times in the past for diabetes because of persistent glycosuria. Kidney ultrasound was unremarkable. Further evaluation showed serum phosphorus 1.8 mg/dL, serum uric acid 1.6 mg/dL, proteinuria 1.95 g/24 hours, fractional excretion of phosphorus 43%, and HbA1c 5.1%. HIV, antinuclear antibody, antiprotei‐nase‐3 antibody, and antimyeloperoxidase antibody were negative. Kidney biopsy was consistent with light‐chain proximal tubulopathy (LCPT), lambda type without cast nephropathy or amyloidosis. Serum and urine protein electro‐phoresis confirmed a monoclonal peak of Immunoglobulin G lambda chain with high serum‐free lambda chain at 169.75 mg/L. Skeletal survey was negative, and bone marrow biopsy showed 8% plasma cells with lambda chain–positive clone. Normoglycemic glycosuria, hyperphosphaturia with hypophosphatemia, hypouricemia, and LCPT were consistent with light‐chain Fanconi syndrome (LCFS). The patient refused treatment, and 6 months after diagnosis his creatinine is stable at 2 mg/dL.
Discussion:
Plasma cell dyscrasias cause an array of kidney disorders including cast nephropathy, AL‐amyloidosis, thrombotic microangiopathy, and LCPT. LCPT classically presents with Fanconi syndrome and is termed LCFS, a constellation of aminoaciduria, normoglycemic glycosuria, uricosuria, hyperphosphaturia, and proximal renal tubular acidosis secondary to crystalline accumulation of light chains in the proximal tubule. Incomplete degradation of the crystallized light chains with subsequent accumulation is the suspected mechanism of kidney injury. Immunofluorescence and electron microscopy can identify crystallization, but ultrastructural immunogold labeling of the light chain is the confirmatory test for LCPT. LCFS is almost always caused by kappa chains, unlike our patient who had lambda‐chain LCFS. The subtle and variable presentations of LCPT make it difficult to diagnose, but left unrecognized, kidney disease and acquired Fanconi syndrome leading to metabolic and bone disease may result.
Conclusions:
Physicians should be aware of causes of persistent glycosuria in the absence of diabetes. Timely evaluation for Fanconi syndrome in a normoglycemic adult with persistent glycosuria is essential to prevent metabolic and bone diseases. Fanconi syndrome in adults is rare and should prompt a thorough hematologic evaluation for plasma cell dyscrasia, as treatment of the underlying dysproteinemia can restore kidney function.
Disclosures:
R. Sinnakirouchenan ‐ none; V. Ramalingam ‐ none; E. Ulozas ‐ none