Thymidine phosphorylase deficiency (MNGIE)

MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) is a rare inherited disease caused by changes in the TYMP gene, which leave the body without enough of the enzyme thymidine phosphorylase. Two compounds, thymidine and deoxyuridine, then build up in the blood and damage the DNA inside mitochondria. Symptoms often begin in childhood or early adulthood. They include severe gut problems such as bloating, vomiting and poor movement of the bowel, marked weight loss, drooping eyelids, weak eye movements, nerve damage in the hands and feet, and hearing loss. It is often first mistaken for an eating disorder or inflammatory bowel disease.

Lab tests linked to MNGIE:

• No results are listed on this page yet.
• Doctors test plasma or urine thymidine and deoxyuridine, which are markedly raised, and thymidine phosphorylase activity in white blood cells, which is very low. Genetic testing for TYMP confirms the diagnosis. An MRI of the brain often shows white matter changes.

How results are read:

• High thymidine and deoxyuridine with very low enzyme activity strongly suggest MNGIE.
• Lactate can be raised, as in other mitochondrial diseases, but this is not specific.
• Carriers with one altered gene copy usually have no symptoms.

When to see a doctor:

• See a specialist about unexplained severe weight loss with ongoing gut symptoms, especially alongside drooping eyelids or numbness in the hands and feet.
• Get urgent care for persistent vomiting with a swollen, painful abdomen.

Clinical takeaway: specialists can establish MNGIE through characteristic rises in plasma thymidine and deoxyuridine, markedly reduced thymidine phosphorylase activity, or two disease-causing TYMP variants.