Clinical Scenario:
A 3-year-old boy is referred for persistent growth failure and progressive genu valgum. He has polyuria and drinks frequently but has no history of recurrent urinary tract infection. Serum creatinine is normal. Investigations show hypophosphataemia, hypokalaemia and a normal-anion-gap metabolic acidosis. His blood glucose is normal, but urine testing repeatedly demonstrates significant glycosuria. Urinary phosphate and uric acid excretion are also increased.
Which of the following best explains the underlying renal abnormality?
A. Generalized proximal tubular reabsorptive defect
B. Isolated defect in distal hydrogen ion secretion
C. Isolated defect in phosphate transport
D. Impaired aldosterone synthesis
E. Reduced glomerular filtration
Correct answer & Explanation:
Correct answer: A. Generalized proximal tubular reabsorptive defect
Explanation
The key is to recognize that this is not simply proximal RTA.
The child has several substances being lost simultaneously:
- Bicarbonate → normal-anion-gap metabolic acidosis
- Phosphate → hypophosphataemia and rickets
- Glucose despite normal blood glucose → renal glycosuria
- Uric acid → increased urinary urate loss
- Potassium → hypokalaemia
This pattern indicates generalized dysfunction of the proximal renal tubule — Fanconi syndrome.
The normal serum creatinine is an important clue: Fanconi syndrome is primarily a tubular reabsorptive disorder and may occur despite preserved GFR, particularly early in the disease.
In a child, once Fanconi syndrome is recognized, an important next step is to search for an underlying systemic/inherited disorder. Nephropathic cystinosis is the most common inherited cause of Fanconi syndrome in children.
Why the other options are wrong
- B. Isolated defect in distal H⁺ secretion — Incorrect: This causes distal RTA, not generalized urinary wasting of phosphate, glucose and uric acid.
- C. Isolated defect in phosphate transport — Incorrect: This can produce hypophosphataemic rickets but does not explain glycosuria, bicarbonate wasting and hypokalaemic acidosis.
- D. Impaired aldosterone synthesis — Incorrect: Type 4 RTA is associated with hyperkalaemia, not hypokalaemia, and does not cause generalized proximal solute wasting.
- E. Reduced GFR — Incorrect: Reduced GFR does not produce this characteristic pattern of inappropriate urinary loss of multiple proximal tubular solutes.
CPSP exam pearl
Do not diagnose Fanconi syndrome from glycosuria alone. The important clue is glycosuria with normal plasma glucose PLUS evidence of wasting of other proximal tubular solutes, particularly phosphate, bicarbonate, uric acid and amino acids.
Reference
Mérida E, et al. Clinical Approach to Proximal Renal Tubular Acidosis in Children. Advances in Chronic Kidney Disease. 2018;25(4):351–357. It specifically discusses pediatric proximal RTA, Fanconi syndrome, its biochemical pattern and cystinosis.
