X-linked liver glycogenosis type II (XLG II) is caused by mutations in PHKA2, the gene encoding the liver alpha subunit of phosphorylase kinase

X-linked liver glycogenosis type II (XLG II) is a recently described X-linked liver glycogen storage disease, mainly characterized by enlargedliver and growth retardation. These clinical symptoms are very similar tothose of XLG I. In contrast to XLG I patients, however, XLG II patients donot show an in vitro enzymatic deficiency of phosphorylase kinase (PHK).Recently, mutations were identified in the gene encoding the liver alphasubunit of PHK (PHKA2) in XLG I patients. We have now studied the PHKA2gene of four unrelated XLG II patients and identified four differentmutations in the open reading frame, including a deletion of threenucleotides, an insertion of six nucleotides and two missense mutations.These results indicate that XLG II is due to mutations in PHKA2. Incontrast to XLG I, XLG II is caused by mutations that lead to minorstructural abnormalities in the primary structure of the liver alphasubunit of PHK. These mutations are found in a conserved RXX(X)T motif,resembling known phosphorylation sites that might be involved in theregulation of PHK. These findings might explain why the in vitro PHKenzymatic activity is not deficient in XLG II, whereas it is in XLG I.