What is a notable clinical manifestation of increased levels of leucine, isoleucine, and valine?

Increased levels of leucine, isoleucine, and valine, which are branched-chain amino acids, are characteristic of maple syrup urine disease (MSUD). This is a rare genetic disorder caused by a deficiency in the branched-chain alpha-keto acid dehydrogenase complex, which leads to the accumulation of these amino acids and their corresponding keto acids in the body.

The notable clinical manifestation associated with this accumulation is a distinctive sweet, maple syrup-like odor in the urine. This odor is due to the presence of elevated levels of these amino acids and their metabolites that are excreted by the kidneys. The unique smell is a hallmark sign that clinicians may recognize when diagnosing MSUD.

The other options do not accurately reflect the clinical features associated with the accumulation of branched-chain amino acids. For example, sweet-smelling breath is typically associated with conditions like diabetic ketoacidosis rather than MSUD. Frequent migraines and increased pigmentation in the skin are also not recognized symptoms of MSUD and do not relate to the biochemical derangement caused by elevated branched-chain amino acids.