CLINICAL, BIOCHEMICAL AND MOLECULAR FINDINGS IN A PATIENT WITH X-LINKED LIVER GLYCOGENOSIS FOLLOWED FOR 40 YEARS

Phosphorylase kinase (PHK) is a regulatory enzyme in glycogen metaboli sm. Mutations in the gene encoding the alpha subunit of PHK (PHKA2) ha ve been shown to be responsible for X-linked liver glycogenosis (XLG). XLG,a frequent type of glycogen storage disease, is characterised by hepatomegaly and growth retardation. Two subtypes of XLG have been des cribed: XLG type I patients have a clear-cut PHK deficiency in liver a nd blood cells, whereas XLG type II patients have a normal or residual activity. Here, we present clinical, biochemical and molecular findin gs on a liver glycogenosis patient in whom the diagnosis XLG II only b ecame clear after enzyme assays in the liver and identification of the disease-causing mutation. A missense mutation replacing arginine at a mino acid position 186 by histidine (R186H) was identified in the PHKA 2 gene. Mutations of the same arginine residue have been previously fo und in at least four other unrelated XLG II patients. Conclusion Argin ine at position 186 of the alpha subunit seems to play an important ro le in the structure or the regulation of PHK. In patients with XLG hav ing normal or residual PHK activity where XLG II is suspected, the ide ntification of mutations in PHKA2 leads to the final classification.