POLG and mitochondrial DNA depletion syndrome 4a: All AHS affected patients reported so far carry one of two linker mutations (p.A467T or p.W748S) in combination with either another linker mutation or a mutation located in the polymerase domain [19], whereas the p.A467T mutation is the most common mutation identified in POLG. It is present in all major POLG-related diseases: Alpers-Huttenlocher disease, ataxia-neuropathy syndromes and PEO.