Metabolic myopathies Flashcards
(33 cards)
What are the three main categories of metabolic myopathies?
Glycogen storage diseases (GSDs) - defects in glycogen metabolism
Fatty acid oxidation disorders (FAODs) - impaired fatty acid utilization
Mitochondrial disorders - respiratory chain dysfunction
What historical clues suggest a metabolic myopathy?
Recurrent rhabdomyolysis (≥2 episodes)
“Second wind” phenomenon (McArdle’s)
Childhood exercise intolerance or “growing pains”
Family history of consanguinity/muscle disorders
How does McArdle’s disease (GSD V) present clinically?
Symptoms: Early fatigue in anaerobic exercise (5-10 mins), painful cramps, “second wind” after rest, myoglobinuria
Exam: 40% develop proximal weakness in later life
Key feature: Absent lactate rise during forearm ischemic test
What genetic mutation is most common in McArdle’s disease?
PYGM gene mutations:
p.Arg50Ter (R50X) in 85% of Caucasians
p.Gly205Ser in 10%
Autosomal recessive inheritance.
What distinguishes Pompe’s disease (GSD II) from other GSDs?
Pathology: Lysosomal acid α-glucosidase deficiency → glycogen accumulation in lysosomes
Clinical: Axial/proximal weakness, respiratory failure, dilated vasculopathy (intracranial aneurysms)
Diagnosis: Dry blood spot enzyme assay > muscle biopsy
What is the “out of wind” phenomenon?
Worsening symptoms with glucose intake before exercise due to inhibited fatty acid metabolism. Pathognomonic for Tarui’s disease (GSD VII) (PFK deficiency).
How do FAODs like CPT II deficiency present?
Triggers: Prolonged exercise, fasting, cold exposure
Symptoms: Rhabdomyolysis 40-120 mins into endurance activity
Diagnosis: Elevated long-chain acylcarnitines (C16-C18), normal interictal CK
What mimics metabolic myopathies (“pseudometabolic” conditions)?
Becker/LGMD muscular dystrophies
Myotonic dystrophy type 2
RYR1 myopathy (malignant hyperthermia risk)
Endocrine disorders (thyroid/Vit D deficiency)
What diagnostic red flags suggest a metabolic myopathy?
CK >5,000 IU/L unlikely to be metabolic (think dystrophy)
Fixed contractures → consider dystrophy/Pompe’s
Myotonic discharges on EMG → Pompe’s or myotonic dystrophy
What are current treatments for late-onset Pompe’s disease?
Enzyme replacement therapy (ERT): Alglucosidase alfa stabilizes walking/respiratory function
Monitoring: Annual pulmonary/functional assessments
UK criteria: Start if CK elevated + weakness; stop if non-ambulant with FVC <30%
What dietary interventions help McArdle’s patients?
Pre-exercise: 37g sucrose 5 mins before activity
Daily: Low-fat, high-carb diet with complex carbs
Avoid: Anaerobic/isometric exercise
Why is genetic testing revolutionizing diagnosis?
Panels screen 50+ myopathy genes simultaneously
Identifies digenic inheritance (“double trouble”)
Reduces need for muscle biopsy (still useful in complex cases)
What anesthesia risk exists for RYR1-related myopathies?
Malignant hyperthermia: Life-threatening reaction to volatile anesthetics/succinylcholine. Requires dantrolene prophylaxis.
What are the diagnostic criteria for McArdle’s disease (GSD V)?
Classic “second wind” phenomenon
Elevated CK even at rest
Absent lactate rise on forearm ischemic test
PYGM gene mutations (p.Arg50Ter in 85% Caucasians)
How does Tarui’s disease (GSD VII) differ from McArdle’s in glucose response?
“Out of wind” phenomenon: Symptoms worsen with glucose preloading due to inhibited fatty acid metabolism
Associated hemolytic anemia from PFK deficiency in reticulocytes
What are the 4 subtypes of GSD III (Cori disease)?
IIIa: Liver + muscle involvement
IIIb: Liver only
IIIc: Selective transferase deficiency (muscle)
IIId: Selective glucosidase deficiency (liver + muscle)
What cardiac complication is pathognomonic for GSD IV (Andersen’s disease)?
Dilated cardiomyopathy with polyglucosan body accumulation in cardiac myocytes
What are the key features of late-onset Pompe’s disease (GSD II)?
Axial/proximal weakness (paraspinal atrophy, scapular winging)
Respiratory insufficiency (nocturnal hypoventilation)
Dilative vasculopathy (vertebrobasilar dolichoectasia)
What genetic finding differentiates riboflavin-responsive MADD?
ETFDH mutations affecting electron transfer flavoprotein:ubiquinone oxidoreductase
What dietary modification is critical in GSD III management?
High-protein diet (3-4g/kg/day) + cornstarch + limited simple sugars
What distinguishes CPT II deficiency from VLCAD deficiency?
CPT II: Normal muscle biopsy, p.Ser113Leu mutation common
VLCAD: Lipid droplets on biopsy, elevated C14:1 acylcarnitines
What are the 3 treatment pillars for metabolic myopathies?
Dietary modification (carb timing, MCT oil)
Graded aerobic exercise
Enzyme replacement (Pompe’s)
What is the diagnostic triad of Myoadenylate deaminase deficiency?
Exercise intolerance without rhabdomyolysis
Normal CK/muscle biopsy
Absent AMP deaminase activity
What 3 findings suggest mitochondrial myopathy rather than GSD/FAOD?
Ptosis/ophthalmoplegia
Multisystem involvement (CNS, hearing)
Ragged-red fibers on biopsy
