MNGIE background

Question 1

What is it?

Answer 1

 Ultra-rare
 Around 200 patients in the world
 Under-diagnosed

Caused by mutation in the nuclear TYMP gene
 Leads to decrease in thymidine phosphorylase
 Leads to accumulation of substrates thymidine and deoxyuridine in both cytosol and plasma
 Imbalances in mitochondrial deoxyribonucleotide pools
 Which causes secondary mitochondrial DNA mutations, causes mitochondria to fail
 Autosomal recessive disease

Question 2

Gastrointestinal symptoms

Answer 2

	Severe gastrointestinal dysmotility 
	Pseudo-obstruction
	Nausea/vomiting
	Chronic abdominal pain
	Premature satiety (fullness)
	Malabsorption
	Bacterial over-growth
	Intestinal perforation
	Loss of muscle mass
	Severe weight loss

Question 3

Neurological symptoms

Answer 3

	Peripheral neuropathy
	Numbness
	Foot drop
	Muscle weakness
	Hearing loss

Question 4

Ocular symptoms

Answer 4

 Ptosis
 Ophthalmoplegia
 Loss of vision

Question 5

Leukoencephalopathy

Answer 5

 Blood brain barrier dysfunction
 Increased white matter water content
 Initially patchy  more confluent
 Asymptomatic?