Abstract
Glycogen storage disease type IX (GSD IX) is a common form of glycogenosis due to mutations in
PHKA1
,
PHKA2
, or
PHKB
and
PHKG2
genes resulting in the deficiency of phosphorylase kinase. The first two genes are X-linked while the latter two follow an autosomal recessive inheritance. The majority of cases of GSD IX are attributed to defects in
PHKA2
which usually cause a mild disease. We report three patients with
PHKG2
-related GSD IX presenting with significant hepatic involvement, fibrosis, and cirrhosis. Interestingly, the homozygosity mapping resolved a dilemma about an erroneously normal phosphorylase kinase activity in patient 1. The novel mutation found in all the three patients (p.G220E) affects the catalytic subunit of the phosphorylase kinase. Increasing evidence shows that patients with
PHKG2
mutations have a severe hepatic phenotype within the heterogeneous GSD IX disorder. Therefore, defect in
PHKG2
should be considered in patients with suspected glycogenosis associated with significant liver fibrosis and cirrhosis.