Nuclear mitochondrial DNA mutations in acute liver failure
Research type
Research Study
Full title
Role of nuclear DNA mutations associated with mitochondrial DNA depletion syndrome in aetiology of acute liver failure in young children.
IRAS ID
148677
Contact name
Nedim Hadzic
Contact email
Sponsor organisation
King's College Hospital NHS Foundation Trust
Research summary
Acute liver failure (ALF) is a rare but potentially life-threatening condition. The commonest causes are infectious (viral), metabolic (Wilson disease), immune mediated (autoimmune, gestation-associated liver disease) or toxic (medications, xenobiotics). Despite extensive investigations aetiology of ALF remains unexplained in around 30-40% of children. In early childhood this proportion is higher, reaching around 60%, presumably due to a more significant contribution of unrecognised genetic conditions. Recently, it has been recognised that mitochondrial DNA depletion syndrome (MDDS) secondary to a number of identified nuclear mitochondrial DNA mutations could be associated with liver disease including viral or medication-associated acute liver failure.
Many MDDS have multiple organ involvement and acute liver failure maybe the first manifestation of this disorder. Other organ involvement may progress later even after liver transplantation. Therefore children with the gene mutation associated with liver disease who underwent liver transplant may carry significantly poorer outcome.
Our aim is to investigate the prevalence of nuclear mitochondrial DNA mutations in children with indeterminate acute liver failure. The 4 nuclear gene mutations that have been identified to cause MDDS and significantly associated with liver disease are POLG, DGUOK, MPV17 and PEO1 (TWINKLE). The presence of these gene mutations may be useful as prognostic marker in children who present with indeterminate acute liver failure. The diagnosis may help in preventing these children from undergoing inappropriate liver transplant (LT) as children who have MDDS, LT may be futile due to other organ involvement that could progress with the disease even after LT.REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
14/EE/1040
Date of REC Opinion
26 Jun 2014
REC opinion
Favourable Opinion