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Cori-Forbe IIIa
Glycogen debranching enzyme defect in muscle & liver
Hepatomegaly, hypoglycemia, growth retardation, progressive skeletal myopathy, cardiomyopathy.
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IIIb
glycogen debranching enzyme defect in liver.
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Anderson IV
Defect in branching enzymes leads to long unbranched insoluble glycogen that precipitates in liver.
Hepatomegaly and liver cirrhosis -> death at age 5.
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McArdle V
Defect in muscle phosphorylase.
- Exercise intolerance & muscle cramps
- no CORI-cycle
- rhabdomyolysis -> renal failure
TX: Glucose before exercise
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HERS VI
Defect in liver phosphorylase
- Mild to moderate hypoglycemia
- mild ketosis
- growth retardation
- prominent hepatomegaly
-
TARUI VII
defect in muscle phosphofructokinase
- Exercise intolerance w/ cramps
- rhabdomyolysis & myoglobinuria
- Gout as Fru-6 -> hexose monophosphate pathway
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VIII
Defect hepatic phosphorylase kinase (x-linked)
- Hepatomegaly
- growth retardation
- elevated liver enzymes
- hypercholesterolemia
- hypertriglyceridemia
- fasting hyperketosis
TX: dextrothyroxine
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Fanconi-Bickel XI
Defect GLUT2.
- Dec Glucose uptake/release by liver
- dec glucose sensing in pancreas
- dec reuptake in renal tubules
- growth failure
- rickets
- osteoporosis
- dwarfism
- hepatomegaly
- moon-shaped face
- fats deposits on shoulder & abd
- fractures
- pancreatitis
- Glucose, aa, phosphate, pro and uric acid in urine
- metabolic acidosis
TX: antiketogenic diet, water, electrolyte, and vitamin D supplementation
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Lysosomal sotrage diseases
- Accumulation of substrate in lysosome & ECM
- prevents autophagosome-lysosome fusion
- inflammation via Toll-receptors
- apoptosis via growth factors
- cholesterol metabolism & insulin signaling affected
- lysosphingolipids interfere with cell signal & cytokines -> apoptosis; giant multinuclear cells
- Ca2+ release after inc Glucose -> exitotoxicity. Low Ca2+ -> apoptosis
-
Lysosomal storage disease tx
Enzyme with Man-6-P binds to cellular receptor -> endocytosis -> transport to lysosome
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Mitochondrial diseases
Muscles and nervous system most affected.
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Pyruvate Dehydrogenase
3 enzymes that could be affected
- lactic & pyruvic acidemia
- lethargy
- poor feeding
- tachypnea
- developmental delay
- seizures
- spasticity
- ataxia
- death
-
Pyruvate DH E1
inactivated by phosphorylation by PDH-kinase.
X-linked recessive
-> lactic acidosis in children
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Leigh syndrome
Mutation in OxPhos or PDH
Early onset progressive neurodegeneration with focal, bilateral lesions in CNS: demyelination, gliosis, necrosis, spongiosis, or capillary proliferation.
lactic acidosis, tachypnea, truncal hyptonia, growth retardation, cardiomyopathy, encephalopathy, myoclonic epilepsy
Inheritance mitochondrial or AR
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LEBER hereditary optic neuropathy
-
Acute or subacute central vision loss leading to central
- scotoma (blind-spot) or blindness in mid-age
- neurologic manifestations in some cases
- susceptibility for tobacco-alcohol amblyopia
- various mutations in mtDNA for complex I, III, and IV
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RAGGED RED FIBERS
Lumps of aggregated mitochondria in muscle biopses, staining red with GOMORI's trichome
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