The boy with massive glucosuria.

A 3.5-year-old boy living in a remote Armenian village was admitted to the hospital in Yerevan in March 2002 with a history of polydipsia since the age of 6 months, bowed legs since he started to walk at the age of 1 year and an increasingly large abdomen. The child was very small [height: 74 cm ( 5.9 SDS)] but alert, had a moonlike face, a grossly enlarged liver (10 cm below the costal margin) and a waddling gait due to severe rickets with genua vara (Figure 1). Psychomotor development was adequate for age. The liver was markedly enlarged at ultrasonography, but of homogeneous structure. The kidneys were large (length: 76mm; normal for height: 45–70mm). Laboratory examination showed proximal tubular dysfunction with generalized amino aciduria, but glucosuria was excessive with 213mmol1⁄4 38.4 g per 24 h or 133 g/1.73m/day (normal: 0.13–0.32 g/1.73m/day) at blood glucose levels of 4.9mmol/l fasting (normal: 3.8–6.4mmol/l) and of 9.4mmol/l after feeding (normal: <7.8mmol/l). Tubular reabsorption of glucose was only 13% (normal: 100%) of the filtered load at normal blood glucose. Serum sodiumwas 128mmol/l (normal: 134–144mmol/l), phosphorus 0.74mmol/l (normal: 1.2–2.1mmol/l) and uric acid 79 mmol/l (normal: 110–350 mmol/l). Elevated values were found for liver enzymes; cholesterol was 7.12mmol/l (normal: 1.6–4.9mmol/l) and triglycerides were 3.15mmol/l (normal: 0.4–1.8mmol/l). We suspected Fanconi–Bickel syndrome (MIM 227810), which is characterized by generalized renal tubular dysfunction with massive glucosuria and by hepatorenal glycogen accumulation [1,2]. Genetic analysis confirmed this diagnosis and revealed homozygosity for a novel missense mutation (GLUT2 c.887 A!G) leading to the substitution of histidine at position 192 by arginine (H192R) and heterozygosity in the parents. The patient markedly improved on treatment with vitamin D2 (16 000 U/day), frequent feedings and a generous intake of fluid and electrolytes.