Dent disease presenting as partial Fanconi syndrome and hypercalciuria.

CASE PRESENTATION A 6-year-old Korean-American boy was found to have asymptomatic proteinuria and glycosuria during routine urinary screening. His birth was complicated by polyhydramnios. His 4-year-old brother was also found to have glycosuria and proteinuria on routine urinalysis (Table 1). There was no history of hematuria, renal failure, hearing loss, or nephrolithiasis. He was taking no medications. There was no other family history of renal disease or renal calculi. Physical examination revealed a healthy-appearing young boy with a normal blood pressure of 90/60 mm Hg and no edema. Physical examination was normal, and there was no evidence of cataracts, rickets, or mental retardation. Height and weight were in the 25th percentiles. Renal ultrasound showed 7.5 cm kidneys with echogenic medullary regions and one echogenic focus suggestive of a calculus. Laboratory examination showed a hematocrit of 34.4% (normal 37–45%), white blood cell count 10.7 10/L (normal 4.5–13.5 10/L) with normal differential, platelet count 527 10/L (normal 150–450 10/L), blood urea nitrogen 15 mg/dL (5.4 mmol/L) (normal 7–18 mg/dL (2.5–6.4 mmol/L)), serum creatinine 0.3 mg/dL, total serum protein 7.6 g/dL (76 g/L) (normal 6–8.2 g/dL (60–82 g/L)), serum albumin 4.3 g/dL (43 g/L) (normal 3.4–5.0 g/dL (34–50 g/L)). The serum electrolytes, including calcium, magnesium, and phosphorus were normal. TCO2 was 25.7 mM (normal 22–32 mM). Serologic testing for antinuclear antibody was negative and the serum complement levels, including C3 and C4, were within normal range. Urinalysis revealed a specific gravity of 1030, pH 5, protein 4300 mg/dL, glucose 100 mg/dL, heme moderate, and leukocyte esterase negative. The urine protein/creatinine ratio was 4.3 and the urine calcium/creatinine ratio was 0.339 (normal o0.200). Urine protein electrophoresis revealed 354 mg/dL of protein of which 26% was albumin with a large fraction of low molecular weight proteins and a markedly elevated b2-microglobulin of 159 000mg/dL (normal 0–300mg/dL). The urinary amino-acid profile showed no abnormality. Urinary uric acid was 633.6 mg/dL (normal 250–750 mg/dL), magnesium 54 mg/24 h (normal 12–293 mg/24 h), phosphorus 880 mg/24 h (normal 400–1300 mg/24 h), and copper 32mg/24 h (normal 3–25mg/24 h). The clinical differential diagnosis included conditions, both inherited and acquired, that impair proximal tubular function producing a partial Fanconi syndrome (glycosuria and low molecular weight proteinuria (LMWP), without proximal renal tubular acidosis, aminoaciduria, or hyperphosphaturia). Acquired conditions to be considered in this age group include heavy metal toxicity, anti-tubular basement membrane nephritis, and other forms of interstitial nephritis. The family history of two affected brothers strongly suggested an inherited disorder, possibly X-linked or autosomal recessive. Inherited forms of Fanconi syndrome to be considered include Dent disease, Lowe syndrome, cystinosis, and a mitochondriopathy. In addition, causes of hypercalciuria such as hyperparathyroidism or excessive calcium intake were considered, although the absence of hypercalcemia and the presence of proteinuria argued against that possibility. Among causes of inherited Fanconi syndrome, Dent disease is the only form that typically manifests marked hypercalciuria. A renal biopsy was performed to determine the cause of the subnephrotic proteinuria and glycosuria. t h e r e n a l c o n s u l t http://www.kidney-international.org