The rarest disease in the world is ribose-5-phosphate isomerase deficiency (RPI deficiency).

• Rarity: As of now, only one confirmed case has been reported in medical literature.

• Nature: It’s a metabolic disorder that affects the body's ability to process carbohydrates properly, due to a deficiency in the enzyme ribose-5-phosphate isomerase.

• Symptoms: The condition led to neurological deterioration, including developmental delays and seizures.

There are other extremely rare diseases—such as Fields Condition (only two known cases) and Methemoglobinemia (in very specific genetic contexts)—but RPI deficiency holds the distinction due to the singular confirmed case.