LOCALIZATION OF A NEW-TYPE OF X-LINKED LIVER GLYCOGENOSIS TO THE CHROMOSOMAL REGION XP22 CONTAINING THE LIVER ALPHA-SUBUNIT OF PHOSPHORYLASE-KINASE (PHKA2)

We describe here a new type of X-linked liver glycogen storage disease . The main symptoms include liver enlargement and growth retardation. The clinical and biochemical abnormalities of this glycogenosis are si milar to those of classical X-linked liver glycogenosis due to phospho rylase kinase deficiency (XLG). However, in contrast to patients with XLG, the patients described here have no reduced phosphorylase kinase activity in erythrocytes and leukocytes, and no enzyme deficiency coul d be found. Linkage analysis of four families with this X-linked type of liver glycogenosis assigned the disease gene to Xp22. Lod scores ob tained with the markers DXS987, DXS207, and DXS999 were 3.97, 2.71, an d 2.40, respectively, all at 0% recombination. Multipoint linkage anal ysis localized the disease gene between DXS143 and DXS989 with a maxim um lod score of 4.70 at theta = 0, relative to DXS987. As both the cla ssical MG gene and the liver Lu-subunit of PHK (PHKA2) are also locate d in Xp22, this variant type of XLG may be allelic to classical XLG, a nd both diseases may be caused by mutations in PHKA2. Therefore, we pr opose to classify XLG as XLG type I (the classical type of XLG) and XL G type II (the variant type of XLG). (C) 1994 Academic Press, Inc.