Glycogen storage disease type I
Biochemistry and nutrition
AssessmentsGlycogen storage disease type I
Glycogen storage disease type I
USMLE® Step 1 style questions USMLE
A 6-month-old girl is brought to the pediatrician’s office for evaluation of an enlarged abdomen. Her parents state they have noticed a bulging, protuberant belly over the past several weeks. Her mother has also noticed she has been increasingly irritable in between her feedings, and she often wakes up crying at night and is only consoled with feedings. During her periods of irritability, the patient is often sweating, which resolves with feeding. She is exclusively breastfed. Her birth was unremarkable; however, she has not been able to sit up or crawl. Her weight is less than the 5th percentile for her age. Temperature is 36.4°C (97.5°F), pulse is 122/min, blood pressure is 86/62 mmHg, and respiratory rate is 48/min. Physical examination reveals a lethargic infant. Facial examination reveals a rounded “doll's face-like” features with enlarged cheeks. Abdominal examination reveals massive and firm hepatomegaly. Genetic testing is performed, revealing a nonsense mutation in the gene encoding the enzyme glucose-6-phosphatase. Which of the following laboratory findings can be expected in this patient, considering the most likely diagnosis?
Glycogen storage disease type I exam links
Content Reviewers:Viviana Popa, MD
Contributors:Salma Ladhani, MD, Evan Debevec-McKenney, Jung Hee Lee, MScBMC, Sean Watts, MD
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?
Now when it’s been a while after a meal, so when you’re fasting, blood sugar levels take a dip. In response, the pancreas secretes glucagon and the adrenal glands secrete epinephrine.
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.