Alkaptonuria as a cause of pseudo-proteinuria in two children evaluated for renal disease

Proteinuria in childhood is a major warning sign of kidney disease and often prompts an extensive diagnostic work-up. However, not all protein detected by routine laboratory methods reflects true renal protein loss, and analytical interference may lead to misinterpretation and unnecessary invasive procedures. Alkaptonuria is a rare autosomal recessive disorder of tyrosine metabolism characterized by lifelong accumulation of homogentisic acid, which is known to interfere with some colorimetric urine protein assays and may cause pseudo-proteinuria. We report two children evaluated in a pediatric nephrology setting because of significant proteinuria. The first patient, who had familial Mediterranean fever, underwent kidney biopsy to exclude amyloidosis before the diagnosis of alkaptonuria was considered after a seemingly minor historical clue provided by the mother. The second patient was followed after a severe episode of hemolytic uremic syndrome, and persistent proteinuria was initially attributed to residual renal damage; however, further evaluation revealed underlying alkaptonuria and a marked discordance between total protein and albumin excretion. These cases illustrate an important diagnostic pitfall and emphasize that, particularly in the presence of discordance between total urine protein and albumin, pseudo-proteinuria should be considered. A simple question such as whether the urine darkens on standing may provide a crucial clue and prevent unnecessary investigations.