Polymerase gamma deficiency (POLG): Clinical course in a child with two stage evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and neuropathological findings of Leigh's encephalopathy

Division of Paediatric Neurology, Centre Hospitalier de Luxembourg, Luxembourg.
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society (Impact Factor: 2.3). 02/2012; 16(5):542-8. DOI: 10.1016/j.ejpn.2012.01.013
Source: PubMed

ABSTRACT 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.
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.
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.

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    • "Interestingly the authors describe that their patient did not respond to glucagon, a response that could be consistent with GDE deficiency depending on the fasting time. Due to the many similarities between our patient and the one previously published (Roels et al. 2009; Scalais et al. 2012), one may speculate whether our findings are genotype specific. A search of the Human DNA Polymerase Gamma Mutation Database ( for p.[A467T]+p.[G848S] revealed 18 additional published cases. "
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