Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy
- Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, 'Bambino Gesu' Children's Hospital, Rome (Italy)
- Division of Metabolism, 'Bambino Gesu' Children's Hospital, Rome (Italy)
- Gastroenterology and Liver Unit, 'Bambino Gesu' Children's Hospital, Rome (Italy)
- Dept. Pathology, 'Bambino Gesu' Children's Hospital, Rome (Italy)
- UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy)
Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: 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.
- OSTI ID:
- 22207573
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 415, Issue 2; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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