title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Paediatric Neurology, Centre Hospitalier de Luxembourg, Luxembourg. scalais.emmanuel@chl.lu
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scalais
authors.forename: Baudouin
authors.initials: B
authors.lastname: Francois
authors.forename: Patrick
authors.initials: P
authors.lastname: Schlesser
authors.forename: Rene
authors.initials: R
authors.lastname: Stevens
authors.forename: Christian
authors.initials: C
authors.lastname: Nuttin
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.forename: Sara
authors.initials: S
authors.lastname: Seneca
authors.forename: Frank
authors.initials: F
authors.lastname: Roels
authors.forename: Gert
authors.initials: G
authors.lastname: Van Goethem
authors.forename: Ann
authors.initials: A
authors.lastname: Löfgren
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
mesh_terms: D001921:Brain / Q000473:pathology*; D002675:Child, Preschool; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D006501:Hepatic Encephalopathy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics* / Q000473:pathology; D017093:Liver Failure / Q000235:genetics* / Q000473:pathology; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human