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What is the underlying molecular problem in McArdle’s disease?
- Myophosphorylase deficiency
- Glycogen storage disease
- Muscle glycogen phosphorylase (PYGM) mutation
- Autosomal recessive
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What is the clinical presentation of McArdle's disease?
- Exercise intolerance (myalgia, fatigue, cramps and muscle swelling).
- Demonstrates second wind phenomenon
- Intense exercise can lead to rhabdo
- CK is raised at rest usually >1000
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What age does McArdles present at?
Adolesence/early adulthood
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What does histology show in McArdle's?
- Accumulation of glycogen on PAS staining
- Absent phosphorylase
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Rods present in the sarcoplasm and/or underneath the sarcolemma?
Sporadic late-onset nemaline myopathy (SLONM)
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Clinical presentation of Sporadic late-onset nemaline myopathy (SLONM)?
- A progressive weakness and atrophy of proximal muscles in the upper and lower limbs, and axial muscles.
- It is accompanied by dyspnoea and/or dysphagia.
- Usually has Head drop
- IgG - MGUS
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What can you do for sporadic late onset nemaline myopathy?
- Steroids work in about 1/3 of them
- Consider stem-cell transplant in the rest
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In what way does HIV nemaline myopathy differ frm sporadic nemaline myopathy?
Facial and resp muscles usually not involved in HIV
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What is the typical finding in Dysferlinopathies?
Cant tiptoe!
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What ethnnic populations suffer with OPMD?
- French canadians from quebec (1:1000)
- Bukhara Jews (1:600)
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What is the molecular and genetic abnormality in OPMD?
- GCN repeat in the PABPN1 gene leading to polyalanine expansion
- >10 repeats leads to disease
- DOES NOT demonstrate anticipation
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Most common cause of death in Duchenne’s and Becker’s?
- Dilated cardiomyopathy
- Advances in response support have ameliorated that as a cause
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What is the clinical difference between DM1 and 2?
- DM2 is proximal limb weakness
- DM1 is distal
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What is the Molecular/genetic difference between DM1 and DM2?
- DM1 - DMPK CTG expansion - shows anticipation
- DM2 - Zinc Finger protein 9 gene (ZNF9) mutations
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Worsening stiffness on sustained exercise or in the cold?
Paramyotonia or HyperkalemicPP
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Stiffness at the beginning of exercise which gets better as you exercise more?
Myotonia Congenita
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Which antibodies can be positive in IBM?
- Anti-cytosolic 50 nucleotidase 1A
- Don’t worry, immunosuppression doesn’t work.
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What is the molecular and genetic abnormality in Welander myopathy?
- TIA1 gene mutation
- Autosomal dominant
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What is the clinical presentation of Welander myopathy?
- Late-onset
- Weakness initially involving the long extensors of the hands, slowly progressing to involve all small hand muscles and the lower legs.
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In what way do Nonaka and Miyoshi myopathies differ from Welander?
They are recessive
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What helps in Hyperkalemic periodic paralysis?
- Salbutamol 1-2 puffs can shorten the attack.
- Avoiding carbohydrate rich snacks and potassium rich foods
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Percussion induced rapid muscle contractions, mounding and rippling can be observed in?
Rippling muscle disease
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Genetic mutation and inheritance in rippling muscle disease?
- Caveolin-3 mutation
- Autosomal Dominant
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Clinical characteristics of Dysferlinopathy (LGMD2B)
- Often very athletic before start of symptoms
- Cant stand on tiptoes from very early on in disease course.
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What is the Emery-Dreifuss muscular dystrophy (EDMD) triad of presentation?
- Contractures
- Humeroperoneal weakness
- Cardiac disease (arrhythmias/cardiomyopathy)
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Whats the gene mutation in emery-dreifuss?
- X-linked recessive version - Emerin
- AD version - Laminin A/C
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What do mutations of the Ryanodine receptor 1 cause?
- LGMD
- Malignant hyperthermia
- Central core disease
- Centronuclear myopathy
- Multiminicore disease
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Commonest cancer that causes Dermatomyositis?
Ovarian
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Risk factors for exertional rhabdo?
- Male
- African ethnicity
- Sickle-cell trait
- Dehydration,
- Higher ambient temperatures,
- Previous heat strokes
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How are the LGMDs divided?
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One of the LGMDs doesnt have cardiac involvement....whcih one?
Calpainopathies LGMD2A
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Which is the most common periodic paralysis?
Hypokalemic PP
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Typical history of Hypokaelic periodic paralysis?
- Onset in adolescence
- Attacks of flaccid paralysis on awakening in morning
- Also triggered by vigorous exercise or high-carb meal the previous day
- Facial and respiratory muscles are spared
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What electrolyte abnormality will you find in Thyroxic periodic paralysis?
Hypokalemia
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Among the sarcoglycanopathies (LGMD2C-F) one muscle group is spared until late on in the disease, which one?
Calf muscles
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Women who are heterozygous for duchenne's have an increased risk of?
cardiomyopathy
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Which muscle of the shoulder girdle is relatively spared in FSHD?
- Deltoid
- FSHD attacks the muscles of scapular fixation and the biceps and triceps.
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Patients with FSHD have a tendency to which vitamin deficiency?
Vit D3
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How do you distinguish Myotonic dystrophy 2 from 1?
- 2 has prominent pain and proximal muscle weakness
- Weirdly, it doesnt have myotonia!?!?
- Theyre both autosomal dominant though
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Whatd the clinical difference between Critical illness myopathy and polyneuropathy?
- Myopathy is proximal
- Polyneuropathy is distal
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Why is colchisine bad for you?
- Attacks microtubules
- Gives you a proximal myopathy and an axonal neuropathy
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What other symptoms do people with LEMS get apart from the weakness?
- Dry mouth (autonomic involvement)
- Pancerebellar syndrome (Theres VGCC in your cerebellum)
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What medications help LEMS?
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Would you give steroids to a duchennes patient?
- Absoloutely!
- Helps with the scoliosis and keeps them walking longer.
- Also helps with some of the resp effects
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Dive bomber pattern on EMG
- Reflects muscles with a channelopathy
- Can occur in
- Myotonic dystrophy 1 and 2
- Congenital myotonia
- HypoKPP
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LGMD1 rundown
- LGMD1A - Myotilin
- LGMD1B - Laminin A/C
- LGMD1C - Caveolin-3
- LGMD1D - Chromosome 6p
- LGMD1E - Chromosome 7q
- Bethlem myopathy - Collagen VI
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LGMD2 rundown
- LGMD2A - Calpain-3
- LGMD2B - Dysferlin
- LGMD2C-F - Sarcoglycans
- LGMD2G - Telethonin
- LGMD2H - E3-ubiquitin Ligase
- LGMD2I - Fukutin-related protein
- LGMD2J - Titin
- LGMD2K - Protein-I-mannosyltransferase 1
- LGMD2L - Fukutin
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Elevated CK, myalgia and raised eosinophils?
- Trichinosis
- Mild gastrointestinal sx followed 1-6 weeks later by symptoms above + puffy eyelids and conjunctival oedema.
- Can get ocular muscle weakness as well as dysarthria and dysphagia depending on where the larvae are depositied via the lymphatics.
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Centronuclear myopathy
- Nuclei are central and the muscle weakness is also central!
- Weakness of face, pharyngeal muscles, ocular muscles and neck.
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Markesberry-Griggs myopathy
- AD
- Distal myopathy
- Titin mutation
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Nonaka myopathy
- AR
- Distal myopathy with foot drop and UL extensor weakness
- GNE mutation.
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Calcaneal protrusions at birth along with weakness, contractures and distal hyperlaxity?
Ullrich's congenital muscular dystrophy
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Muscle-brain-eye disease says whats affected. Which other AR congenital syndrome is like this?
Walker-Marburg
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What are the AD Distal myopathies?
- Welander
- Tibibal muscular dystrophy
- Scapuloperoneal muscular dystrophy
- Desmin myopathy
- Gower-Laing
- Markesbery-Griggs
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What differentiates Thomsen's and Beckers?
- Thomsen's - AD - presents earlier but is less severe
- Becker's - AR - Presents later but is more severe and associated with weakness.
- Both respond well to Mexiletine
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MND like presentation in late 40's with liver failure?
Debranching enzyme deficiency
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In what way do Nonaka and Miyoshi differ from each other?
- Miyoshi is a dysferlinopathy - so they cant tip toe
- Nonaka gives them weak tib anteriors so they have foot drop. (GNE mutation)
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Riboflavin transporter deficiencies...?
- AR conditions affecting the RFVT2 and RVFT3 genes
- Previously called Brown-vialetto-von laere and fazio-londe.
- Lower cranial nerve involvement
- Sensory ataxia
- Generalised weakness including face and resp muscles
- Sensorimotor neuropathy
- High dose riboflavin arrests or improves the condition
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What gene mutation leads to Congenital myotonia/paramyotonia?
CLCN1 - chloride channel
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How would you manage dermatomyositis?
- Muscle biopsy early doors (upregulation of MHC class 1)
- Immunosupresssion
- Hunt for tumours for 2-3 years
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