Clinical, biochemical and molecular findings in a patient with X-linked liver glycogenosis followed for 40 years

Abstract

Arginine at position 186 of the alpha subunit seems to play an important role in the structure or the regulation of PHK. In patients with XLG having normal or residual PHK activity where XLG II is suspected, the identification of mutations in PHKA2 leads to the final classification.

Complete Genomic Structure and Mutational Spectrum of PHKA2 in Patients with X-Linked Liver Glycogenosis Type I and II

“…However, patients with XLG I show a clear in vitro enzyme deficiency of PHK in erythrocytes, leukocytes, and liver (Huijing and Fernandes 1969), whereas XLG II patients show normal or even elevated in vitro PHK enzyme activity in erythrocytes and leukocytes and varying activity in liver (Hendrickx et al 1994). Both types of XLG have been shown to be caused by mutations in the PHKA2 gene, which encodes the liver a subunit of PHK (Hendrickx et al 1995(Hendrickx et al , 1998Hirono et al 1995;van den Bergh et al 1995;Burwinkel et al 1996Burwinkel et al , 1998. The XLG I mutations include four nonsense mutations (Hendrickx et al 1995;Burwinkel et al 1998), two frameshift mutations (Burwinkel et al 1998), one splice-site mutation (Hendrickx et al 1995), three missense mutations (van den Bergh et al 1995;Burwinkel et al 1998), and three in-frame deletions (van den Bergh et al 1995;Burwinkel et al 1998), whereas the XLG II mutations include eight missense mutations (Hirono et al 1995;Burwinkel et al 1996Burwinkel et al , 1998Hendrickx et al , 1998, a deletion of one amino acid, and an insertion of two amino acids .…”

Two Cases of X-linked Liver Glycogenosis in Hunan Province: Transmission from the Undiagnosed Maternal Grandfather

“…Both types of XLG have been shown to be caused by mutations in the PHKA2 gene. Mutations of PHKA2 have been reported in some western countries, Korea, and Japan [4][5][6]. In this report, we present two cases in a family with XLG-I in China.…”

“…However, since that XLG can be divided into two subtypes based on the PHK activity in the erythrocytes and leukocytes, we have to go further in the diagnosis. The mutation p.E1125K in PHKA2 was previously validated as the cause of the XLG-I subtype [4]. Therefore, the final diagnosis of the two patients is XLG-I.…”

“…It is a complex enzyme which consists of four different subunits α, β, γ and δ. These subunits together form a hexadecameric structure (α, β, γ, δ) 4 . The γ subunit harbors the site for the catalytic activity which is regulated by the phosphorylation of the α and β subunit and by the interaction with the δ subunit, which is a calmodulin for Ca 2+ regulation [1].…”

Multiple voxel 1H MR spectroscopy of phosphorylase-b kinase deficient patients (GSD IXa) showing an accumulation of fat in the liver that resolves with aging

“…However, the clinical picture caused by GSD IXa generally is milder than that in the other hepatic glycogen storage diseases, with the exception of phosphorylase deficiency (GSD VI) [6]. The clinical features of GSD IXa are hepatomegaly, growth retardation, delay in motor development, hypotonia, elevated serum transaminases, hypercholesterolemia, hypertriglyceridemia, fasting hyperketosis and hypoglycemia [5,[7][8][9][10][11][12][13]. Other features like splenomegaly, liver cirrhosis, doll facies, osteoporosis, neurologic disease, elevated serum lactate, metabolic acidosis and renal tubular acidosis have been described as part of the clinical picture of phosphorylase b kinase deficiency, but the frequency of their presence is very low.…”