Glycogen storage diseases (GSD) are inherited metabolic diseases characterized by glycogen accumulation in the liver and/or muscles. Among liver GSDs, glycogen phosphorylase-phosphorylase kinase deficiency is responsible for GSD Type IX or VI. GSD Type IX results from a glycogen phosphorylase kinase deficiency and is primarily caused by a damage to one of the four different genes coding for the enzyme subunits. The most commonly affected gene is PHKA2, located on X chromosome. These GSDs are usually suspected in the event of hepatomegaly, elevated liver transaminases, and increased postprandial lactate levels, with a trend towards hypoglycemia, though fasting is often well tolerated. The diagnosis is generally made based on enzyme activity measurement in red blood cells and confirmed by genetic analysis. In boys, however, some variants are not characterized by a decreased erythrocyte activity. As a result, and if clinical manifestations are suggestive, the genes involved in GSD IX and VI must be analyzed in order to exclude this diagnosis, with the PHKA2 gene being analyzed first, followed by the PYGL gene (GSD VI).

This report presents our assumptions and diagnostic reflections regarding a clinical case with hepatomegaly, as well as elevated transaminases and postprandial lactate levels. The genetic study allowed us to detect a mutation in the PHKA2 gene that is responsible for the X-linked GSD Type IX, though this condition had previously been excluded.

What is already known about the topic?

The diagnosis of glycogen storage disease Type IX can generally be made based on enzyme activity measurement in red blood cells.

What does this article bring up for us?

• Normal erythrocyte phosphorylase kinase activity does not exclude the diagnosis of GSD Type IX.

• Among boys, some variants are not associated with decreased erythrocyte enzyme activity. Thus, if clinical manifestations are suggestive, the genes involved in glycogen storage diseases IX and VI should be analyzed in order to exclude this diagnosis.

• In this article, we have also reviewed the differential diagnosis of liver glycogen storage diseases

Practical recommendations

• Think of a glycogen storage disease type IX when a patient presents a hepatomegaly, elevated liver transaminases and postprandial high lactate. A tendency to hypoglycemia may be observed through a glycemic profile, but fasting is generally well tolerated.

• Even if the phosphorylase kinase activity is normal in erythrocytes, it is useful to conduct a genetic analysis of PHKA2 and PYGL genes, among boys, to formally exclude a type IX glycogen storage disease.

Key Words

Glycogen storage diseases, phosphorylase kinase, PHKA2, hepatomegaly, hypoglycemia, lactic acid, ketones