Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy.
Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.
Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, Rome, Italy.
Marzia
M
Bianchi
Teresa
T
Rizza
Daniela
D
Verrigni
Diego
D
Martinelli
Giulia
G
Tozzi
Alessandra
A
Torraco
Fiorella
F
Piemonte
Carlo
C
Dionisi-Vici
Valerio
V
Nobili
Paola
P
Francalanci
Renata
R
Boldrini
Francesco
F
Callea
Filippo Maria
FM
Santorelli
Enrico
E
Bertini
Rosalba
R
Carrozzo
D004272:DNA, Mitochondrial / Q000235:genetics*; D017809:Fatal Outcome; D006801:Humans; D007223:Infant; D007625:Kearns-Sayre Syndrome / Q000235:genetics* / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion
D004272:DNA, Mitochondrial