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These are all autosomal recessive. I will not talk about them in order for reasons I’ll discuss.
For starters, I’ll group the following two together because the USMLE likes you to differentiate them:
Von Gierke disease (type I) = ↓ glucose-6-phosphatase (G6Pase deficiency; NOT G6PD deficiency)
Cori disease (type III) = ↓ α-1,6-glucosidase (debranching enzyme)
Von Gierke is the most severe glycogen storage disorder. There’s hepatic steatosis with hepatomegaly, very severe fasting hypoglycemia and increased blood lactate.
The increased blood lactate is the most important part.
In contrast to von Gierke disease, Cori disease DOES NOT have increased blood lactate. That is the highest yield point you need to know.
| Seemingly “severe” presentation in a young child with lactic acidosis → von Gierke disease
Seemingly “not that severe” presentation in a child where they specifically say no lactic acidosis → Cori disease Likewise: Bicarbonate (HCO3–) in the normal range (22-28)? Yes, in normal range → no lactic acidosis → Cori disease Bicarbonate (HCO3–) in the normal range (22-28)? No, bicarb is low (<22) → due to lactic acidosis → von Gierke disease |
With von Gierke disease, patients need to avoid both fructose and galactose because consumption of either will lead to buildup of glycolytic intermediates and depletion of available hepatic phosphate.
Therefore:
| Do glucose levels rise after giving fructose? Yes, glucose levels rise → intact gluconeogenesis → Cori
Do glucose levels rise after giving fructose? No, glucose levels don’t rise → gluconeogenesis impaired due to ↓ G6Pase → von Gierke |
Pompe disease (type II) = ↓ lysosomal α-1,4-glucosidase (acid maltase)
Literally (and I’m not joking), the only presenting feature you need to know about Pompe is that it causes cardiomyopathy. Essentially, if you get a glycogen storage disease question and they mention anything about the heart in a young child, the answer is Pompe.
| Heart problems in a glycogen storage disease question = Pompe disease |
Pompe is the only glycogen storage disease where the deficient enzyme is notably located in the lysosome. For the others, choose cytosol. By all means, yes, the lysosome is inside the cytosol, but I’m just making a point that for whatever reason the USMLE is known to ask this weird point of differentiation.
McArdle disease (type V) = ↓ myophosphorylase (muscle glycogen phosphorylase)
Pretty much 100% of the time, the vignette they’ll give you is a late-teen or young adult who performs some form of intense exercise (e.g., shoveling snow, sprinting) and then gets painful muscle cramps and red/dark urine.
If they ever ask you about an electrolyte abnormality in this situation, the answer is hyperkalemia secondary to rhabomyolysis. It’s the myoglobin in the urine that makes it dark.
Dipstick of the urine will be (+) for blood, but urinalysis will reveal no RBCs. The dipstick is merely detecting the myoglobin.
| Myoglobinuria causes a false (+) for blood on dipstick. Therefore, e.g., ++ blood on dipstick, but 0-1 RBCs per high-power field on light microscopy (negative RBCs), think rhabdo. |
If they ask you about the type of renal injury secondary to McArdle, the answer is acute tubular necrosis secondary to the nephrotoxic effects of myoglobin.
| Acute tubular necrosis = muddy brown, granular casts on urinalysis. These are sloughed PCT tubular cells, not RBCs.
ATN is a type of intra-renal failure with a BUN/Cr <20, a FENa >1%, and ↓ urine osmolality. |
The USMLE doesn’t ask about glycogen storage disease type IV (Andersen disease) for whatever reason.
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