NOTES

NOTES
GLYCOGEN STORAGE DISEASES
(GSD)

GENERALLY, WHAT ARE THEY?

PATHOLOGY & CAUSES DIAGNOSIS
▪ Metabolism disorders → pathological LAB RESULTS
intracellular accumulation of glycogen/ ▪ Cell count, hormones, metabolites
metabolic products
▪ AKA dextrinoses/glycogenoses Muscle/liver biopsy
▪ Impaired glycogen metabolism → cells ▪ With periodic acid-Schiff stain
without energy between meals → cell ▪ Detects glycogen
dysfunction, death
▪ Tissues most dependent on carbohydrates OTHER DIAGNOSTICS
most affected ▪ Genetic testing
▫ Liver, heart muscle, brain, skeletal
muscle Fasting test for clinical orientation
▪ Hypoglycemia
CAUSES
▪ Enzyme deficiency in glycogen synthesis/ TREATMENT
breakdown
▪ Genetic, environmental factors OTHER INTERVENTIONS
▪ Corrective diet
COMPLICATIONS ▪ Symptomatic therapy (cell growth factors)
▪ Rhabdomyolysis; cardiomyopathy; ▪ Enzyme replacement therapy for symptom
atrioventricular block (AV) block; renal relief
failure (myoglobin from dead muscle cells
impairs renal function); lactic acidosis
due to energy being generated from
triglycerides, protein; hyperuricemia, gout
(lactic, uric acid excreted via same renal
transport mechanism)

SIGNS & SYMPTOMS

▪ Symptomatic at birth/early adulthood
▪ Hypoglycemia, hyperlipidemia
(compensatory mechanism for
hypoglycemia), fatigue, hypotonia (floppy
baby), hepato/splenomegaly, hypoglycemia
→ seizures, metabolic acidosis →
hyperventilation, vomiting

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 GLYCOGEN STORAGE DISEASE
TYPE I (GSD I)
osms.it/GSD-I
accumulation of G6P (lactate + pyruvate →
PATHOLOGY & CAUSES G6P via gluconeogenesis) → compensatory
hyperventilation, vomiting
▪ AKA von Gierke disease
▪ Pathological intracellular accumulation Hypertriglyceridemia
of glucose-6-phosphate (G6P) due to ▪ Compensate for chronically low insulin
impaired glycogenolysis, gluconeogenesis
Hyperuricemia
▪ Final product of both mechanisms: G6P
▪ Excess G6P in pentose phosphate pathway
▪ Most common glycogen storage disease
→ high blood concentrations of uric acid
→ competes with other organic acids (e.g.
TYPES lactic acid) for excretion in kidneys

GSD Ia
▪ Mutation of G6PC gene DIAGNOSIS
GSD Ib
DIAGNOSTIC IMAGING
▪ Mutation of G6PT1 gene
Ultrasound
GSD Ic
▪ Enlarged liver, kidneys
▪ Mutation of SLC17A3 gene

LAB RESULTS
CAUSES
▪ G6P deficiency → G6P trapped inside cell Liver biopsy with periodic acid-Schiff stain
(too polar to pass through cell membrane) ▪ Glycogen detection
→ severe hypoglycemia
▪ Autosomal recessive mutations OTHER DIAGNOSTICS
▪ Genetic testing
COMPLICATIONS
▪ Hepatomegaly; kidney enlargement; Fasting test
atherosclerosis due to hyperlipidemia; ▪ Hypoglycemia, doesn’t respond to glucagon
growth, development disorders; gout, injection
kidney damage due to hyperuricemia

TREATMENT
SIGNS & SYMPTOMS
OTHER INTERVENTIONS
Fasting hypoglycemia ▪ Diet consisting of frequent meals high in
▪ Blood glucose level regulation impaired carbohydrates
(esp. between meals) → low insulin → high ▪ Regulation of metabolic complications
cortisol, glucagon

Metabolic acidosis
▪ Lactate cannot convert into pyruvate due to

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GLYCOGEN STORAGE DISEASE

TYPE II (GSD II)
osms.it/GSD-II

PATHOLOGY & CAUSES DIAGNOSIS

▪ AKA Pompe disease DIAGNOSTIC IMAGING
▪ Pathological accumulation of glycogen in
X-ray
lysosome
▪ Cardiomegaly
▪ Mainly affects skeletal muscles, heart; also
liver, nervous system
LAB RESULTS
TYPES ▪ ↑ creatine kinase, lactic dehydrogenase,
alanine transaminase, aspartate
Early/infantile onset transaminase
▪ Few months after birth, typically 4–8;
Muscle biopsy
progression much faster
▪ Glycogen detection
Late onset
▪ > two years; as late as 50–60 OTHER DIAGNOSTICS
ECG
CAUSES
▪ Arrhythmia, cardiomyopathy
▪ Autosomal recessive disease caused by
mutation on chromosome 17
▪ Acid alpha-glucosidase deficiency → TREATMENT
glycogen cannot break down, accumulates
in lysosome → lysosome bursts → OTHER INTERVENTIONS
glycogen, lysosomal enzymes leak into
▪ Enzyme replacement therapy
cytoplasm → cell dysfunction, death

COMPLICATIONS
▪ Rhabdomyolysis, completely impaired
motor function, respiratory/heart failure,
development disorders

SIGNS & SYMPTOMS

▪ Progressive muscle weakness, respiratory
insufficiency due to weakened diaphragm
function, arrhythmia, cardiomegaly,
cardiomyopathy, hepatomegaly, hypotonia,
recurrent chest infections

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 GLYCOGEN STORAGE DISEASE
TYPE III (GSD III)
osms.it/GSD-III

PATHOLOGY & CAUSES DIAGNOSIS

▪ AKA Cori’s disease, Forbes disease, limit DIAGNOSTIC IMAGING
dextrinosis
Ultrasound
▪ Intracellular pathological accumulation of
incompletely broken down glycogen → ▪ Hepatosplenomegaly
buildup of dextrins (intermediate products
of glycogen breakdown) → osmotic LAB RESULTS
pressure of cell increases → pulls water in,
damages cell Liver/muscle biopsy with periodic ac-
▪ Affects liver, skeletal muscles, heart id-Schiff stain
▪ Glycogen detection
TYPES
OTHER DIAGNOSTICS
GSD IIIa ▪ Genetic analysis
▪ Liver, muscles

GSD IIIb TREATMENT

▪ Liver

GSD IIIc
OTHER INTERVENTIONS
▪ High glucose, protein diet
▪ Liver, muscles

CAUSES
▪ Autosomal recessive disease
▪ Deficiency of glycogen debranching
enzyme (GDE): amylo-alpha-1,6-
glucosidase, 4-alpha-glucanotransferase

COMPLICATIONS
▪ Hepatosplenomegaly, cardiomegaly,
developmental disorders, liver failure

SIGNS & SYMPTOMS

▪ Hypoglycemia, hypotonia, arrhythmia,
cardiomyopathy, rhabdomyolysis, muscle-
related symptoms (later in life), may
resemble GSD I

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GLYCOGEN STORAGE DISEASE

TYPE IV (GSD IV)
osms.it/GSD-IV

PATHOLOGY & CAUSES DIAGNOSIS

▪ AKA Andersen’s disease DIAGNOSTIC IMAGING
▪ Intracellular accumulation of abnormally
Prenatal ultrasound
formed glycogen
▪ Fetal hydrops, hydramnion
▪ Improper glycogen synthesis → buildup
of polyglucosan bodies (unbranched ECG
long chains of glucose) → precipitation
▪ Heart abnormalities
of polyglucosan bodies → foreign body
reactions, increased osmotic pressure →
cell damage LAB RESULTS
Liver/muscle biopsy with periodic ac-
CAUSES id-Schiff stain
▪ Autosomal recessive mutation of GBE1 ▪ Glycogen detection
gene on chromosome 3
▪ Deficiency of 1,4-alpha-glucan branching
enzyme (GBE)
OTHER DIAGNOSTICS
▪ Genetic analysis

Echocardiography
SIGNS & SYMPTOMS
▪ Heart abnormalities
▪ Fatal perinatal neuromuscular
▫ Fetal hydrops, hydramnion; hypotonia; TREATMENT
reduced infant mobility; cardiomyopathy
present at birth; death approx. one OTHER INTERVENTIONS
month after birth
▪ Only symptomatic treatment available
▪ Childhood neuromuscular
▫ Variable intensity, life expectancy;
manifests in childhood; myopathy,
cardiomegaly
▪ Progressive hepatic
▫ Failure to thrive (FTT); liver cirrhosis;
portal hypertension; ascites; death few
months after birth
▪ Non-progressive hepatic
▫ Similar to progressive hepatic type,
symptoms less intense; cirrhosis not
present; can live into adulthood
▪ Congenital muscular
▫ Manifests shortly after birth;
cardiomegaly; life expectancy few
months

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 GLYCOGEN STORAGE DISEASE
TYPE V (GSD V)
osms.it/GSD-V

PATHOLOGY & CAUSES DIAGNOSIS

▪ AKA McArdle’s disease LAB RESULTS
▪ Intracellular pathological accumulation of
Muscle biopsy
glycogen in muscle tissue
▪ With periodic acid-Schiff stain
▪ Cannot release glucose-1-phosphate →
↓ glycolysis, cell energy status, Na+/K+ ▪ Glycogen detection
ATPase function → osmotic cell imbalance
→ cell damage OTHER DIAGNOSTICS
▪ Affects only muscle tissue ▪ Genetic analysis

TYPES
TREATMENT
Early onset
▪ More severe symptoms, progression OTHER INTERVENTIONS
▪ Only symptomatic treatment available
Adult onset
▪ Less severe symptoms, progression

CAUSES
▪ Autosomal recessive disease
▪ Deficiency of myophosphorylase (muscle-
specific isoform of glycogen phosphorylase)

COMPLICATIONS
▪ Renal failure due to myoglobinuria from
rhabdomyolysis
▪ Muscle contractures due to fibrosis caused
by extensive damage

SIGNS & SYMPTOMS

▪ Exercise intolerance, fatigue,
rhabdomyolysis, muscle fibrosis
▪ ‘’Second wind’’ phenomenon: shift in
metabolism during exercise → sudden
burst of energy, despite being out of breath

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