AssessmentsGlycogen storage disease type I
Glycogen storage disease type I
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A 5-year-old boy is brought to the emergency department by this mother because of recurring episodes of sweating, pallor, and loss of consciousness. His medical history is relevant for a nonspecific convulsion at birth. Upon further interrogation with the mother, she mentions that the symptoms are worse on awakening and decrease after meals. On physical exam, the boy looks well-appearing with chapped and rounded cheeks, protruding abdomen, and hepatomegaly. His temperature is 36.7°C (98°F), pulse is 120/min, respirations are 30/min, blood pressure is 110/70 mmHg, and pulse oximetry on room air shows an oxygen saturation of 96%. A liver biopsy shows high glycogen content with normal structure. Laboratory studies are obtained and shown below.
A deficiency of which of the following enzyme activities is the most likely cause of the findings in this patient?
Glycogen storage disease type I, also called Von-Gierke’s disease, is a genetic disorder caused by a mutation in the glucose 6 phosphatase gene on chromosome 17.
The end result is that glycogen can’t be broken down into glucose in liver cells, so glucose metabolism goes awry, resulting in symptoms like low blood sugar, weakness and poor growth.
Glucose is such an important energy source, that our body stores excess glucose in liver cells and skeletal muscle cells in the form of glycogen.
Glycogen is basically an enormous molecule or polymer, that’s made up of glucose molecules linked together by glycosidic bonds.
And glycogen has a main chain, as well as multiple branches sprouting off of it.
These branches allow glycogen to be compact and also allow it to rapidly add and remove glucose to and from the big glycogen molecule.
Talk about a molecular sugar rush!
Now, glucose molecules are usually added to glycogen in response to insulin, which is secreted by the pancreas after meals.
That’s when there’s high blood sugar, or plenty of glucose floating around in the bloodstream.
So, it makes sense for some of this glucose to be stored as glycogen, right?
It turns out that glucagon tells the liver cells to break glycogen down into individual glucose molecules, and epinephrine tells skeletal muscle cells to do the same.
In both the liver and skeletal muscle cells, glycogen breakdown begins with the branches, and it results in the release of glucose-6-phosphate - which is just like glucose, but with a phosphate clinging to it.
In liver cells, an enzyme called glucose-6-phosphatase removes the phosphate off of the 6th carbon, releasing free glucose into the bloodstream, for all the organs and tissues to enjoy - very generous!
Skeletal muscle cells, on the other hand, can simply use glucose-6-phosphate for energy - but they lack glucose 6 phosphatase, so they don’t share any of it with other organs and tissues!
Now with glycogen storage disease type I, there’s not enough glucose 6 phosphatase, so glucose-6 phosphate can’t get that phosphate molecule cleaved off and become glucose, so it can’t leave liver cells for fasting energy.
But liver cells have plenty of biochemical pathways all working hard at the same time, so glucose-6-phosphate can be used to make something else instead.
So first, glucose-6-phosphate can be shunted towards glycolysis, which is the biochemical pathway that uses glucose-6-phosphate to make pyruvate and acetyl-CoA.