eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
3/2018
vol. 69
 
Share:
Share:
more
 
 
abstract:
Original paper

Histopathological liver findings in patients with hepatocerebral mitochondrial depletion syndrome with defined molecular basis

Maciej Pronicki, Dorota Piekutowska-Abramczuk, Dariusz Rokicki, Katarzyna Iwanicka-Pronicka, Wiesława Grajkowska

Pol J Pathol 2018; 69 (3): 292-298
Online publish date: 2018/11/20
View full text
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
Mitochondrial DNA depletion consisting of the systemic reduction of mtDNA copy number in cells may have a heterogenous genetic basis, resulting from a pathogenic change in the nuclear genes involved in mtDNA synthesis. The mode of inheritance is autosomal recessive. Severe hepatocerebral disease represents one of many different clinical forms of so-called mitochondrial depletion syndrome (MDS). We present the liver histopathology of 13 children who eventually died in the course of hepatocerebral MDS confirmed molecularly, harbouring mutations of DGUOK, MPV17, and POLG genes. Material comprising eight autopsy and five liver biopsy specimens showed a moderately reproducible pattern of parenchymal damage, which we consider potentially helpful in the differential diagnosis and planning of the diagnostic investigation in families of children who died due to early-onset acute liver failure and encephalopathy.
keywords:

mitochondrial DNA depletion, liver failure, POLG1, DGUOK, MPV17

references:
Moraes CT, Shanske S, Tritschler HJ, et al. mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am J Hum Genet 1991; 48: 492-501.
Morris AA, Taanman JW, Blake J, et al. Liver failure associated with mitochondrial DNA depletion. J Hepatol 1998; 28: 556-563.
El-Hattab AW, Scaglia F, Craigen WJ, et al. MPV17-Related hepatocerebral mitochondrial DNA depletion syndrome. In: GeneReviews®[Internet]. Adam MP, Ardinger HH, Pagon RA, et al. (eds.). University of Washington, Seattle 1993-2018.
Piekutowska-Abramczuk D, Pronicki M, et al. Hepatocerebral depletion syndrome in children – methodology, study results and recommendations. Standardy Medyczne Pediatria 2016; 13: 869-876.
Huttenlocher PR, Solitare GB, Adams G. Infantile diffuse cerebral degeneration with hepatic cirrhosis. Arch Neurol 1976; 33: 186-192
Naviaux RK, Nguyen KV. POLG mutations associated with Alpers’ syndrome and mitochondrial DNA depletion. Ann Neurol 2004; 55: 706-712.
Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995; 19: 1409-1417.
Piekutowska-Abramczuk D, Pronicki M, Strawa K, et al. Novel c.191C>G (p.Pro64Arg) MPV17 mutation identified in two pairs of unrelated Polish siblings with mitochondrial hepatoencephalopathy. Clin Genet 2014; 85: 573-577.
Pronicka E, Wêglewska-Jurkiewicz A, Pronicki M, et al. Drug-resistant epilepsia and fulminant valproate liver toxicity. Alpers-Huttenlocher syndrome in two children confirmed post mortem by identification of p.W748S mutation in POLG gene. Med Sci Monit 2011; 17: CR203-209.
Pronicka E, Wêglewska-Jurkiewicz A, Taybert J, et al. Post mortem identification of deoxyguanosine kinase (DGUOK) gene mutations combined with impaired glucose homeostasis and iron overload features in four infants with severe progressive liver failure. J Appl Genet 2011; 52: 61-66.
Harding BN. Progressive neuronal degeneration of childhood with liver disease (Alpers Huttenlocher syndrome). A personal review. J Child Neurol 1990; 5: 273-287.
FEATURED PRODUCTS
Quick links
© 2018 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe