Priority 14 from the Mitochondrial Disease PSP

UNCERTAINTY: How do the different genetic mutations cause the symptoms people experience with mitochondrial disease? (JLA PSP Priority 14)
Overall ranking	14
JLA question ID	0095/14
Explanatory note	Not available
Evidence	None identified
Health Research Classification System category	Metabolic and Endocrine

Extra information provided by this PSP
Original uncertainty examples	Why do retinal ganglion cells die in Leber's hereditary optic neuropathy? ~ I carry only 20% and have been told I wouldn’t suffer symptoms but I feel I do, muscle fatigue and tiredness, is this true ? ~ Which other systems are most likely to be affected and how? ~ Like to understand low thyroid T3 connection is there a thyroid and T3 connection to the disease ~ How do genetic mutations in POLG cause epilepsy? What determines phenotypic presentation of mitochondrial disease? ~ Why does 3243 cause MELAS in some people and MIDD in others?
Submitted by	19 x Healthcare Professionals, 6 x Carers

Extra information provided by this PSP

Original uncertainty examples

Why do retinal ganglion cells die in Leber's hereditary optic neuropathy? ~ I carry only 20% and have been told I wouldn’t suffer symptoms but I feel I do, muscle fatigue and tiredness, is this true ? ~ Which other systems are most likely to be affected and how? ~ Like to understand low thyroid T3 connection is there a thyroid and T3 connection to the disease ~ How do genetic mutations in POLG cause epilepsy? What determines phenotypic presentation of mitochondrial disease? ~ Why does 3243 cause MELAS in some people and MIDD in others?

Submitted by

19 x Healthcare Professionals, 6 x Carers

PSP information
PSP unique ID	0095
PSP name	Mitochondrial Disease
Total number of uncertainties identified by this PSP.	42 (To see a full list of all uncertainties identified, please see the detailed spreadsheet held on the JLA website)
Date of priority setting workshop	19 January 2020