5oxoprolinuria

5oxoprolinuria, also known as pyroglutamic aciduria, is a metabolic disorder characterized by the accumulation of 5-oxoproline in the blood and urine. This condition can arise from two primary causes: inherited enzyme deficiencies or acquired factors.

Inherited forms are rare genetic disorders that affect specific enzymes involved in the glutathione metabolic pathway. The most common inherited type is a deficiency in glutathione synthetase, an enzyme crucial for the synthesis of glutathione, a vital antioxidant and detoxifying agent. When this enzyme is deficient, the precursor 5-oxoproline builds up. Another, less common inherited form, involves a deficiency in 5-oxoprolinase, an enzyme that breaks down 5-oxoproline.

Acquired 5oxoprolinuria is more frequent and is often seen in individuals with conditions that increase oxidative stress or deplete glutathione levels. This includes chronic malnutrition, liver disease, sepsis, certain cancers, and prolonged use of some medications, particularly acetaminophen (paracetamol) in high doses. In these cases, the body's demand for glutathione increases, leading to its depletion and a subsequent rise in 5-oxoproline.

Symptoms of 5oxoprolinuria can vary widely depending on the underlying cause and severity. In inherited forms, especially severe glutathione synthetase deficiency, symptoms can include neurological problems such as developmental delay, seizures, and intellectual disability. Acquired forms may present with more subtle symptoms or be associated with the underlying condition. Diagnosis is typically made through biochemical testing of urine and blood for elevated 5-oxoproline levels. Treatment focuses on addressing the underlying cause. For inherited forms, management is supportive. For acquired forms, discontinuing offending medications or treating the underlying illness is paramount.