Enzyme Deficiencies Chart
Red=distinguishing (though not inclusive of all key) features
Enzyme Pathway it is Presentation of pt/description of scenario
part of
Glucose 6- Glycogenolysis Von Gierkes Type 1 GSD. Hepatomegaly, hepatic
phosphatase steatosis, fasting hypoglycemia, lactic acidosis,
hyperuricemia, hyperlipidemia
Acid α- Glycogenolysis Pompe Type 2 GSD. Normal glucose. Severe
glucosidase//Aci cardiomegaly. Profound hypotonia. Macroglossia.
d Maltase Glycogen accum in lysosomes on mm biopsy
(visualized with EM). Often presents in early infancy—
weak suckling, weak holding up of head in feeding,
FTT.
Acyl-CoA Fatty acid B- Sx apparent after intense fasting only (induces state of
dehydrogenase oxidation catabolism requiring FAO); pt with hypoketotic
hypoglycemia (=low ketones in blood bc cant be
produced through FAO, and low gluc) —lethargy, V,
hepatomegaly, low gluc, 0 acetoacetate, inc AST ALT
Protein Glycogenesis Activates glycogen synthase by dephosphorylation and
phosphatase inhibits glycogen phosphorylase, so promotes
glucoseglycogen. Protein phosphatase is activated
by PI3K pathway stimulated upon insulin binding to
TKR.
Debranching Glycogenolysis Cori Type 3 GSD. Multibranched polysaccharides
enzyme (glycogen molecs) with abnormally short outer
chains(=limit dextrins) found in hepatocyte cytosol.
hepatomegaly, hypotonia, low ht and wt despite food
intake, labs with ketotic hypoglycemia (i.e. not the FAO
deficiency kind), hepatic fibrosis on biopsy.
Any important associations/tx/notes
Expressed only in liver and kidney, so does not affect
muscles—no hypotonia, etc.
Is a lysosomal E that breaks down small amts of
glycogen that end up in lysosomes (most is degraded in
cytosol) in cells with high glycogen like mm and liver.
Has 1,4 and 1,6 glucosidase activity (i.e. like
debranching E). normal glucose bc does not affect the
liver primarily, though does along with mm.
See cardiomegaly bc cardiac myocytes and skel mm are
esp susceptible to ballooning glycogen-filled lysosomes
compressing and inhibiting contractile units
Presentation is same for deficiency of any type of acyl-
CoA dehydrogenase involved in FAO. Carnitine
deficiency looks similar bc prevents FA entry in mito for
B-O.
Conversely, glycogen synthase inhibited by protein
kinase A (PKA—activated by glucagon; activates
glycogen phosphorylase via GP kinase)
Short branches indicates that glycogen phosphorylase is
fning and thus able to remove G-1-P residues from
branches until 4 units remain, but then debranching
enzymes are deficient and cannot remove remaining
units. Hypotonia also helps distinguish from other GSD
i.e. Von Gierke
Glycogen Glycogenolysis McArdles Type 5 GSD if lose muscle GP. Weakness, Normal glycogen structures with normal length
phosphorylase fatigue, pain, cramps w/ exercise/mm use (dec branches seen in cells bc are missing first step enzyme,
exercise tolerance). Myoglobinuria. No inc in lactate rather than later debranching enzymes or other Es, so
after exercise. Excess of normally structured glycogen no cant get any change in glycogen branch length or
on mm biopsy (not short limit dextrins like Cori). structure. GP activated when PKA activates GP kinase
Hers Type X GSD if lose hepatic GP. Mild hypoglycemia, activation upon glucagon stim of Gs-AC pathway.
ketosis, hepatomegaly. Excess of normally structured GlucagonGs-ACPKAGPKGP activation.
glycogen in hepatocytes on biopsy. No mm sx.
Pyruvate TCA Lactic acidosis. Neuro deficits. Developmental delays, PDH links glycolysis to TCA by taking pyruvate from
Dehydrogenase failure to thrive, episodic seizures. glycolysis and making A-CoA that can be used in TCA.
Inherited inborn error of metabolism. Diet—high fat low carb moderate protein IOT force
ketone body prod from fat and AA metab and dec
glucose content so no pyruvate is prod so no lactate is
prod. Can supplement diet with lysine or leucine=the
only exclusively ketogenic AAs that are metab to the
ketone body precursor A-Coa and cannot be metab to
pyruvate, so cannot be shunted into LA pathway, thus
doesn’t further inc serum lactate which is good, unlike
glucogenic AAs which are metab to prod pyruvate or
other TCA intermediates that can be converted to
glucose by gluconeogenesis, which would then result in
inc serum lactate bc the pyruvate generated from the
glucose via glycolysis cannot go into TCA bc of PDH
deficiency, so gets shunted to LA pathway.
Pyruvate Kinase Glycolysis Chronic hemolytic anemia Converts PEP to pyruvate for subsequent TCA.
Hemolysis bc RBCs use glycolysis aerobic respiration as
main energy source.
Glycogen Glycogenolysis Activates glycogen phosphorylase, so Stim by PKA, Ca-CAM, Ca.
phosphorylase glycogenglucose.
kinase