PMID- 22342071
OWN - NLM
STAT- MEDLINE
DCOM- 20130204
LR  - 20171116
IS  - 1532-2130 (Electronic)
IS  - 1090-3798 (Linking)
VI  - 16
IP  - 5
DP  - 2012 Sep
TI  - Polymerase gamma deficiency (POLG): clinical course in a child with a two stage 
      evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and 
      neuropathological findings of Leigh's encephalopathy.
PG  - 542-8
LID - 10.1016/j.ejpn.2012.01.013 [doi]
AB  - AIMS: Description of the clinical course in a child compound heterozygous for 
      POLG1 mutations, neuropathology findings and results of dietary treatment based 
      on fasting avoidance and long chain triglycerides (LCT) restriction. RESULTS: At 
      3(1/2) months of age the patient presented with severe hypoglycemia, 
      hyperlactatemia, moderate ketosis and hepatic failure. Fasting hypoglycemia 
      occurred 8 h after meals. The hypoglycemia did not respond to glucagon. She was 
      supplemented with IV glucose and/or frequent feedings, but developed liver 
      insufficiency which was reversed by long-chain triglyceride (LCT) restriction. 
      Alpha-foeto-protein (AFP) levels were elevated and returned to low values after 
      dietary treatment. Liver biopsy displayed cirrhosis, bile ductular proliferation, 
      steatosis, isolated complex IV defect in part of the liver mitochondria, and 
      mitochondrial DNA depletion (27% of control values). Two heterozygous mutations 
      (p. [Ala467Thr] + p. [Gly848Ser]) were found in the POLG1 gene. At 3 years of age 
      she progressively developed refractory mixed type seizures including a focal 
      component and psychomotor regression which fulfilled the criteria of Alpers 
      syndrome (AS) although the initial presentation was compatible with infantile 
      myocerebrohepatopathy spectrum (MCHS). She died at 5 years of age of respiratory 
      insufficiency. Neuropathologic investigation revealed lesions in the right 
      striatal area and the inferior colliculi typical for Leigh's encephalopathy. 
      CONCLUSION: The present patient showed an evolution from infantile MCHS to AS, 
      and dietary treatment seemed to slow the progression of liver failure. In spite 
      of the late clinical features of AS, it extends the neuropathological spectrum of 
      AS and polymerase gamma deficiency (POLG) to Leigh syndrome lesions.
CI  - Copyright (c) 2012 European Paediatric Neurology Society. Published by Elsevier 
      Ltd. All rights reserved.
FAU - Scalais, Emmanuel
AU  - Scalais E
AD  - Division of Paediatric Neurology, Centre Hospitalier de Luxembourg, Luxembourg. 
      scalais.emmanuel@chl.lu
FAU - Francois, Baudouin
AU  - Francois B
FAU - Schlesser, Patrick
AU  - Schlesser P
FAU - Stevens, Rene
AU  - Stevens R
FAU - Nuttin, Christian
AU  - Nuttin C
FAU - Martin, Jean-Jacques
AU  - Martin JJ
FAU - Van Coster, Rudy
AU  - Van Coster R
FAU - Seneca, Sara
AU  - Seneca S
FAU - Roels, Frank
AU  - Roels F
FAU - Van Goethem, Gert
AU  - Van Goethem G
FAU - Lofgren, Ann
AU  - Lofgren A
FAU - De Meirleir, Linda
AU  - De Meirleir L
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20120217
PL  - England
TA  - Eur J Paediatr Neurol
JT  - European journal of paediatric neurology : EJPN : official journal of the 
      European Paediatric Neurology Society
JID - 9715169
RN  - 0 (DNA, Mitochondrial)
RN  - EC 2.7.7.7 (DNA Polymerase gamma)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
RN  - EC 2.7.7.7 (POLG protein, human)
SB  - IM
MH  - Brain/*pathology
MH  - Child, Preschool
MH  - DNA Polymerase gamma
MH  - DNA, Mitochondrial/genetics
MH  - DNA-Directed DNA Polymerase/*deficiency
MH  - Diffuse Cerebral Sclerosis of Schilder/*genetics/pathology
MH  - Disease Progression
MH  - Fatal Outcome
MH  - Female
MH  - Hepatic Encephalopathy/genetics/pathology
MH  - Humans
MH  - Infant
MH  - Leigh Disease/*genetics/pathology
MH  - Liver Failure/*genetics/pathology
MH  - Mutation
EDAT- 2012/02/22 06:00
MHDA- 2013/02/05 06:00
CRDT- 2012/02/21 06:00
PHST- 2011/08/17 00:00 [received]
PHST- 2012/01/11 00:00 [revised]
PHST- 2012/01/26 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2013/02/05 06:00 [medline]
AID - S1090-3798(12)00017-7 [pii]
AID - 10.1016/j.ejpn.2012.01.013 [doi]
PST - ppublish
SO  - Eur J Paediatr Neurol. 2012 Sep;16(5):542-8. doi: 10.1016/j.ejpn.2012.01.013. 
      Epub 2012 Feb 17.