Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 
years ago. It is an autosomal recessive, developmental mitochondrial DNA 
depletion disorder characterized by deficiency in mitochondrial DNA polymerase 
gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and 
liver disease. In two unrelated pedigrees of Alpers' syndrome, each affected 
child was found to carry a homozygous mutation in exon 17 of the POLG locus that 
led to a Glu873Stop mutation just upstream of the polymerase domain of the 
protein. In addition, each affected child was heterozygous for the G1681A 
mutation in exon 7 that led to an Ala467Thr substitution in POLG, within the 
linker region of the protein.