Glycogen storage disease type VII (Tarui disease): a case report presenting a PFKM variant previously described only...

Glycogen storage disease type VII (GSD-VII), or Tarui disease, is a rare autosomal recessive disorder caused by biallelic loss-of-function variants in the PFKM gene encoding the muscle isoform of phosphofructokinase (PFK), a key enzyme of the glycolytic pathway. PFK deficiency impairs glycogen and glucose metabolism in skeletal muscle and erythrocytes, causing exercise intolerance, exertional myalgia, and myoglobinuria, and, in some cases, fixed proximal muscle weakness, as well as haemolytic anaemia. We report the case of an Italian woman with genetically confirmed GSD-VII harbouring a homozygous missense variant in PFKM (NM_000289.6:c.550C>T, p.Arg184Trp). This variant was previously identified in Wachtelhund dogs, a spontaneous animal model of PFK deficiency, but never reported in patients so far. PFK activity in skeletal muscle (PFKM) was found severely decreased and ultrastructural analysis revealed glycogen accumulation and mitochondrial alteration, supporting the pathogenetic role of the identified variant.