Why can a shortage of the final product in a metabolic pathway cause disease?

In a metabolic pathway, food is processed through a series of steps by enzymes that convert substrates into specific products. These products subsequently serve as the substrate for the next enzyme in the sequence.1

A shortage of the final product occurs when an enzyme within this pathway is missing or exhibits diminished activity, effectively blocking the route. Because metabolic pathways are often interlinked, this blockage prevents the formation of the necessary final product, which can lead to disease.1

The clinical consequences of such metabolic imbalances are often severe, potentially resulting in intellectual disability, seizures, organ failure, or other developmental anomalies, depending on which specific enzyme is dysfunctional. Furthermore, the blockage may cause the accumulation of upstream substrates, which can become toxic, or trigger the activation of dormant, minor pathways that produce additional harmful substances.1