Inherited tubulopathies: Case

This infant has nephropathic cystinosis presenting as Fanconi syndrome. The failure to thrive, the polyuria and polydipsia, the hypophosphataemic rickets with frontal bossing, widened wrists and bowed tibiae, the normal anion gap metabolic acidosis, the hypokalaemia, and the glycosuria with a normal blood glucose together signal a generalised failure of the proximal tubule. Cystinosis is the commonest inherited cause of Fanconi syndrome in children, and without cysteamine it progresses to end-stage kidney disease in the first decade. ^[1]

Clinical findings

The clinical picture is one of global proximal tubular dysfunction with its metabolic consequences. The proximal tubule normally reabsorbs the bulk of the filtered load, and its failure spills glucose, phosphate, amino acids, low molecular weight proteins and bicarbonate into the urine. The glycosuria with a normal blood glucose, the hypophosphataemia with rickets, and the normal anion gap acidosis from bicarbonate wasting are the hallmarks. The polyuria from the osmotic diuresis and the concentrating defect drives the dehydration and the vomiting that contribute to the failure to thrive. ^[2]

The rickets is the skeletal expression of the phosphate wasting. The chronic hypophosphataemia, compounded by the acidosis that leaches mineral from bone, produces the bowing of the legs, the widened wrists and the frontal bossing. The child is reluctant to walk because of bone pain. In cystinosis there may be added photophobia from corneal crystal deposition and a fair complexion, and the candidate should ask about these and examine the eyes, because the corneal crystals are a defining feature that the slit lamp reveals before any blood test returns. ^[1]