Autosomal recessive inborn error of metabolism of
glycogen producing a heterogeneous group of hepatic glycogenoses with mild
clinical manifestations and benign course.
Glycogen Phosphorylase Deficiency; Hepatic Phosphorylase
Kinase Deficiency; Hers Syndrome; Liver Phosphorylase Deficiency; X-Linked
Liver Glycogenosis; Glycogenosis type VI; Phosphorylase b Kinase Deficiency.
Inborn error of metabolism consisting of a deficiency of
liver phosphorylase (classic form) or other enzyme defects of the
phosphorylase cascade system such as phosphorylase b kinase deficiency
(formerly GSD IX, GSD VIII by McKusick) and adenosine 3',5'-cyclic
monophosphate (cyclic AMP)-dependent protein kinase deficiency (formerly GSD
Accounts for about 30% of all GSD, of which approximately
75% result from the X-linked recessive form of phosphorylase kinase
deficiency. Incidence up to 0.1% in the Mennonite population (3%
incidence of specific splice-site mutation in the liver phosphorylase gene
of this religious group).
Autosomal recessive (classic form;
accounts for about 25% of cases)
X-linked recessive form (phosphorylase kinase deficiency). Phosphorylase b kinase genes are
multimeric (four different subunits, each coded by a unique gene located on
different chromosomes). Different isoforms of each enzyme with
differential tissue expression exist.
Deficiency of liver phosphorylase, the ratelimiting
enzyme of glycogenolysis, is activated by an enzyme cascade
by a succession of enzymes resulting in
insufficient liberation of glucose from the glycogen molecule.
Neoglycogenesis is not affected. Even though the enzyme deficiency is
usually incomplete, mild fasting hypoglycemia and associated hyperketosis
with ketonuria are frequent.
Enzyme deficiency demonstrated on liver biopsy.
Associated biologic disorders include mild hyperlipidemia,
hypercholesterolemia, and, to a lesser extent, hypertriglyceridemia.
Elevated serum transaminases with no other evidence of liver dysfunction is
frequent. Molecular diagnostic testing is used to identify carriers and
Typically, symptomatology becomes apparent in
children at the age of 1 to 5 years, who present with a protuberant abdomen, growth
and mild motor retardation, mild fasting hypoglycemia, and hypotonia. Some
patients are asymptomatic, but physical abdominal examination reveals
hepatomegaly, which may be massive. Severe hypoglycemia is rare. Mild
cardiomyopathy may occur in some patients.
Check blood glucose level, liver function and
cardiac function. Assess degree of hypotonia.
Anesthetic management in this condition
has not been described, but no particular problems would be predicted except
for the potential for severe hypotonia. Dextrose-containing fluid may be
used in patients at risk for hypoglycemia. If hypotonia is present, neuromuscular
blocking agents should be titrated to effect (nerve stimulator) and depending on the
planned procedure, postoperative mechanical ventilation may be required.
No agents specifically
contraindicated. Cis-atracurium should be preferred in patients with
altered liver function.
Other glycogen storage
Burwinkel B, Bakker HD, Herschkovitz E, et al: Mutations in the liver
glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet
Cox JM: Anesthesia and glycogen-storage ...