Muscle Disease: Diagnostic workup

Acquired: Inflammatory, Endocrine/Metabolic, Toxic, Infectious

Hereditary: LGMD, Dystrophinopathy, Metabolic, Myotonic Dystrophy and Channelopathies, Congenital Myopathy, Congenital Muscular Dystrophy, Other: FSHD, OPMD, Distal Myopathies

Disorder Features Lab Investigations
HEREDITARY
Mitochondrial myopathy   Lactate, urine organic acids, plasma amino acids
Carnitine deficiency   Serum carnitine
Periodic Paralysis   K+ in an episode
Acid Maltase   Alpha-glucosidase
   
Arginine:glycine amidinotransferase (AGAT) deficiency (creatine deficiency syndrome) Developmental delay, epilepsy, myopathy Dx: Low guanidinoacetate (GAA) in body fluids (urine, plasma) Tx: Oral creatine      
ACQUIRED
Sarcoid   ACE,CXR, Eos on CBC, ESR, hypogammaglobulins, anergy on ppd, high urine Ca(more often than serum calcium)
Inclusion Body Myositis   *NT5C1A autoantibodies (70% sens, 90% specific?-more resp weak, facial, dysphagia) *Cd4:cd8 ratio reduced. Much cheaper than flow cytometry almost perfect surrogate T cell large granular lymphocytosis Cd57,cd8 positive T cells Tclgl autoimmune causes pancytopenia Bottom line. If low blood counts check cd4:cd8  
PM/DM   ANA, RF, ENA, CRP/ESR
SLONM (sporadic Late Onset Nemaline Myopathy) proximal/axial weakness (spine pain), respiratory weakness, dysphagia/diplopia possible; asymmetric IgG Monoclonal myopathy (treat IVIg, autologous SCT)
HIV association(treat prednisone)
Myositis confirmed   HIV (usually presenting as a polymyositis) HTLV1 (rare myositis) HepB&C (rare myositis) Lyme (rare myoSITIS)-serum, CSF antibody
Necrotizing myopathy PMID: 27086869 *anti-HMGCR autoantibodies *anti-SRP antibody -if these are positive it is much less likely underlying malignancy (though still possible)
*anti-HMGCR autoantibodies Mohassel 2018. insidious onset responsive to IVIgCK>1000, LGMD(+/- scapular), disease onset over years (3+), degen/regen on biopsy; neg genetics
Eosinophilic   CBC – incr Eo, anemia
Amyloid   UPEP/SPEP, Congo Red Bx
Thyroid Dysfunction   TSH, T3, T4
Parathyroid/Vitamin D   Vit D, Ca, PO4, Mg, Albumin
Uremic   Beta2microglobulin, hyper PTH malnutrition, VitD def, high metals(Al), low PO4
Statin Myositis PMID: 27038110 *No patient with severe self-limited cerivastatin-related myopathy had anti-HMGCR autoantibodies *Statin intolerance improved when vitamin D deficiency treated Riche2016 *Alirocumab praluent proprotein convertase subtilisin/kexin type9 PCSK9 inhibitor subcutaneous q2-4weeks. Statin intolerant or muscle diseases.   *anti-HMGCR autoantibodies

Myotonic Discharges (on EMG) Myopathy

  • DM1 (DMPK)
  • DM2(Zinc Finger 9)
  • Paramyotonia congenita (CLCN1, SCN4A)
  • Myotonia congenita(CLCN1)
  • Dynamin 2 associated myopathy (pubmed 29105112)
    • DNM2 (centronuclear myopathy)

Mitochondrial disease notes

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  • Retinitis pigmentosa – night blindness
  • SN hearing loss
  • DM2
  • PEO ptosis
  • Brain – IQ, epilepsy, migraines, movement disorders
  • GI – constipation, emesis
  • cardiac – CD, CMO
  • nephron-RTA, nephrotic, glomerulosclerosis
  • PN Dem, axonal
  • PYR decarboxylase common in ojicree
  • Adult 80%mito
  • Child 80% nuclear DNa
  • MELAS; <40 yo acute onset, IV arginine/citrilline
  • VPA affects mito – causes liver failure in ??POLG??
  • statin affects mitto??
  • labs:
  • CSF lactate/PYR ratio>20
  • PAAcids: high alanine
  • UOAcids: dicarboxylic acid?, methylglutajkjhkjhkjh acid
  • MRI basal ganglia calcifications
  • MRI GRE
  • electron transport train in TO