Front, Search, Index, Links, Pathology, Molecules, Syndromes, Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info

DISTAL WEAKNESS IN MYOPATHIES

Distal Myopathies: Hereditary⁷

Welander (Late onset type I) distal myopathy

• Genetics¹⁰
  • Not allelic with Miyoshi myopathy & LGMD 2B
  • Finnish & Swedish patients have shared haplotype
  • Homoozygotes: Weakness is more severe & proximal
• Epidemiology
  • Especially common: Mid-Sweden & Finland gene frequency 1/4000
  • Penetrance: Relatively low due to late age of onset
• Onset
  • Age: Usually > 40 years; Median 5th decade; Range 20 to 77
  • Location
    • Arms; Wrist & Finger extensors: Most common
    • Legs (Foot drop): 25%
• Clinical: Typical disease
  • Weakness
    • Hands > Legs in most
    • Muscles involved: Long finger extensors; Intrinsic hand; Thumb & index-finger
    • Progression to legs: Toe & ankle extensors
    • Only rarely proximal weakness
  • Tendon reflexes: Reduced at ankles
  • Slow progression with normal life span
  • Sensory loss: Some patients; Subclinical neuropathy common
  • Autonomic: Altered peripheral vasomotor response after vasoconstriction
• Subset with more severe disease
  • ?Homozygotes
  • Rapid progression
  • Early leg & proximal weakness
• Laboratory
  • CK: Normal or mildly elevated
  • EMG: Myopathic; Some irritability
  • Muscle Pathology
    • Chronic myopathic: Varied fiber size; Splitting
    • Rimmed vacuoles: Variably present
    • Tubulo-Filamentous inclusions (15 to 18 nm): Sarcoplasm & muscle fiber nuclei
    • Neurogenic changes
  • Sural nerve: Aδ fiber loss

Finnish (Tibial) (Late onset type IIa; Udd) distal myopathy

• Epidemiology
  • Finland: Large population with same mutation
  • Other regions: French, Belgian & Spain families
• Genetics
  • Finnish population
    • Probably arose from single ancestor
    • 5 to 15 per 100,000 population
    • Mutation: 11 base pair deletion of nucleotides 293,269 to 293,279 (In terminal exon)
  • Allelic with
    • LGMD 2J
    • Dilated cardiomyopathy 1G
    • Myopathy with early respiratory failure: R279W mutation
    • Congenital myopathy + Fatal dilated cardiomyopathy
  • Genotype-Phenotype
    • Same (11 bp) mutation may produce different patterns of weakness
      • Most common: Tibial MD
      • Other: Proximal; Posterior leg
• Onset age
  • Heterozygotes
    • 4th to 8th decade; Most in 40's
    • Many remain asymptomatic
  • Homozygotes: Childhood; LGMD 2J
• Distribution of weakness
  • Legs: Anterior tibial selectively involved
  • Arms
    • Never hand weakness in Finnish patients
    • Some Non-Scandinavian families with hand weakness
  • Proximal weakness: 15%; Mild
• Progression
  • Slow: Foot drop 10 to 15 years after onset when long toe extensors become weak
  • Proximal legs may become weak late in disease
  • Quadriceps weak in rare male
  • Many remain ambulatory
    • Earlier onset (2nd decade) may lose ambulation in 3rd to 6th decade
  • Homozygotes: Loss of ambulation by 3rd decade
• Cardiomyopathy
• Laboratory
  • CK: Mild elevation or normal
  • MRI: Selective fatty replacement of muscles
    • Early: Anterior tibial; Gluteusn minimus
    • Later: Gastrocnemius
• Pathology: Dystrophic (100%)
  • Muscle fibers: Size variation; Splitting; Internal nuclei
  • Basophilia
  • No inflammation
  • Rimmed vacuoles (30%): Contain degenerative cytoplasmic debris & organelles
  • Calpain 3: Reduced
  • Apoptosis in muscle nuclei
  • Anti-titin antibodies
    • Normal binding for most
    • Binding to C-terminal epitope reduced

Markesbery (Late adult onset type IIb) distal myopathy

• Epidemiology: English, French & Finnish families
• Genetics
  • Mutation: A165V; Common in European families
  • Allelic with
    • ZASP myofibrillar myopathy
    • Dilated cardiomyopathy ± Isolated non-compaction of left ventricular myocardium
• Onset: > 40 years
• Clinical
  • Weakness
    • Early: Distal legs
    • Hands: Distal finger & wrist extensors
    • Late: Proximal arms & legs
  • Progression
    • Slow: Slower in Finnish tibial type
    • Disability common
  • Cardiomyopathy: Occasional patient
• Laboratory
  • Serum CK: Normal or Slightly elevated
  • Muscle pathology: Rimmed vacuoles

Hereditary Inclusion Body Myopathy (IBM2; Nonaka) : Recessive

• Nosology: Same disorder as Nonaka distal myopathy
• Genetics: Mutations in GNE gene
  • GNE: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
  • Mutations
    • Usually missense
    • Iranian-Jewish families: Homozygous for Met712Thr
    • Japanese (Nonaka): V572L (60%; Founder effect); Homozygous or Heterozygous
    • Other families: Heterozygous; Missense or occasional Stop
    • Location: Epimerase or kinase domain
    • Other mutations in epimerase domain cause: Sialuria
      • Dominant inheritance
      • Functional defect: Loss of feedback inhibition
• GNE protein: Bifunctional
  • Catalyzes 1st 2 steps in synthesis of N-acetylneuraminic (sialic) acid: Rate-limiting step
  • Epimerase activity: N-terminal
  • Kinase activity: C-terminal
  • Tissue expression
    • Full length protein: Liver; Salivary glands; Intestinal mucosa
    • Shorter form (exon 4 missing)
      • Predominantly expressed in skeletal muscle
      • Present in similar levels in control & myopathy patients
  • Mutants: No correlation between disease pattern and changed enzyme activity
• Epidemiology
  • Iranian-Jewish families: Prevalence in Jews of Persian ancestry: 1:500
  • Other families: Mexico; India; Bahamas; Georgia
• Clinical
  

  from M Sadeh

  Quadriceps sparing CT of thigh in HIBM2

  • Onset: 2nd or 3rd decade
  • Weakness
    • Early: Peroneals
    • Distal & Proximal
    • Lower extremity
      • Onset: Peroneal weakness (Anterior distal legs)
      • Then: Hips & Hamstrings
    • Upper extremity: Shoulder girdle; Wrist extension; Hands
    • Sparing: Quadriceps; Deltoids
      • Weak in some patients: Disease progression
    • Neck flexors may be weak
    • Cranial nerves: Spared
      • Ptosis: Rare
      • Facial weakness: Occasional patient
    • Progression: slow
      • Disability within 10 to 20 years of onset
      • Often become wheel chair dependent
      • Weakness may remain distal or involve proximal muscles of arms legs or neck
• Laboratory
  • CK: Mild elevation, 2x to 5x
  • Urine sialic acid: Not elevated
  • EMG: Spontaneous activity; Myopathic potentials
  • MRI: Quadriceps sparing
• Muscle Pathology
  • Myopathic: Varied muscle fiber size
  • Vacuoles: Red-rimmed
    • Contain paired helical filaments
    • Constituents: βAPP; Ubiquitin; Phosphorylated t; ApoE
    • ? Autophagic
  • 15 to 18 nm filamentous inclusions in cytoplasm & nucleus
  • Myopathic groups: Vacuolar & small fibers clustered in regions
  • Inflammation uncommon, but occasionally present¹¹
  • α-Dystroglycan staining: Reduced¹³

Miyoshi (Early adult onset distal myopathy type II)

From: C Angelini
Miyoshi distal myopathy: Straight legs & Small calves

• Genetic associations
  • Allelic with: Limb-girdle muscular dystrophy 2B
  • Genetic heterogeneity
    • ? Some families linked to chromosome 10 & other loci
• Protein: Dysferlin
  • Skeletal muscle > Heart
  • Attached to cell membrane
• Clinical features
  • Presymptomatic: Mild gastrocnemius wasting
  • Early Adult Onset: Teens to 38 years
  • Weakness & Wasting
    • Posterior Legs: Gastrocnemius; Soleus
    • Symmetric
    • Arms & Proximal muscles involved late
    • Calf wasting
    • Progression: Related to disease duration
    • Asymmetry in families not linked to 2p
• Laboratory
  • CK: Very high up to 20,000
  • MRI
    • Selective involvement of hamstring, gastrocnemius & soleus
    • Early muscle edema
  • Pathology: Dystrophic Muscle
    • Necrosis & degeneration of muscle fibers
    • Endomysial connective tissue: Increased in more involved muscles
    • Muscle fibers: Size variation; Splitting
    • No vacuoles
    • Inflammation
      • Perimysial & perivascular cell infiltrates
      • Variable: May occur in some muscles but not others
• Variant: Anterior tibial onset
  • Epidemiology: Spanish family
  • Dysferlin mutation: 5966delG
  • Onset: 14 to 28 years
  • Weakness: Rapidly progressive
  • Serum CK: Very high
  • Muscle: No vacuoles; Absent dysferlin

Gowers (Laing; Early adult onset distal myopathy type III; MPD1)^3,4

• MYH7 mutations
  • General location
    • LMM region
    • Exons 32, 34, 35, and 36
  • Specific mutations: Arg1500Pro, Lys1617del, Ala1663Pro, Leu1706Pro & Lys1729del
  • Predicted effect: Disrupts
    • Ability of myosin tail to form normal coiled coil structure
    • Myosin dimerization: Altered structure of thick filament
  • Other MYH7 mutations produce
    • Hyaline body myopathy
    • Hypertrophic cardiomyopathy with ventricular arrhythmias
    • Hypertrophic cardiomyopathy with core myopathy
• MYH7 protein
  • Present in type I (Slow) muscle fibers
• Epidemiology
  • Australian, German, Italian & Austrian families
• Possible associations
  • Locus near oculopharyngeal muscular dystrophy: No PABP2 mutations
  • ? Similar to "Childhood onset distal myopathy"
• Clinical Features
  • Onset
    • Age
      • Common: Childhood or Young adult; 1.5 to 26 years
      • Occasional: As late as 6th decade
      • Interfamilial variation
    • Steppage gait
  • Weakness: Intrafamilial variation
    • Legs
      • Ankle dorsiflexion: Often severe with foot drop
      • Hanging big toe
      • Proximal muscles may be involved
    • Neck: Sternocleidomastoids & Neck flexors
    • Hands
      • Finger (esp 5th) & wrist extensors
      • Onset: 3rd to 5th decade; 5 to 10 years after legs
      • Later: Infraspinatus & Supraspinatus
      • Intrinsic hand muscles normal
    • Later in course: Some families
      • Neck flexors; Hip & Shoulder abductors & external rotators
      • Face: Mild
    • Usually symmetric: Asymmetry reported
  • Tendon reflexes: Reduced at ankles; Present elsewhere
  • Muscle discomfort: Some patients
  • Muscle size: Anterior tibial usually atrophic
  • Progression
    • Slow
    • Proximal weakness: Legs, Neck flexors, Abdominal muscles
    • Mild disability at later age
  • Tremor: Hands, then postural
  • ? Peripheral neuropathy with hypomyelination: Some patients
  • Cardiomyopathy
    • Dilated or Hypertrophic
• Laboratory
  • CK: Normal or Mild elevation
  • EMG: Myopathic; Some spontaneous activity
  • Pathology
    • Myopathic: Varied fiber size; Internal nuclei
    • Type I muscle fibers: Small; Grouped
    • Vacuoles: None in most patients; Autophagic rimmed reported
    • Intranuclear tubulofilamentous inclusions: 15 to 20 nm
    • Some muscle fibers (3%) express both fast & slow myosin
    • Distal muscles may be more abnormal
  • MRI: Atrophy & later Increased signal in tibialis anterior & EHL
• Variant: Distal myopathy with Hypertrophic cardiomyopathy¹⁹
  • Mutation: Val606Met; Homozygous
  • Later onset: 6th decade
  • Muscle hypertrophy: Anterior tibial
  • Hypertrophic cardiomyopathy

Distal dystrophy with rimmed vacuoles

• Epidemiology: 2 Italian families
• Onset: Late teens to 50's; Occasional asymptomatic patient in 60's
• Weakness
  • Early: Distal legs
  • Distribution
    • Most involved: Distal legs > Knee extensors + flexors & Intrinsic hand muscles
    • Least involved: Face; EOM; Forearm flexors & Proximal upper extremity muscles
  • Progression
    • To proximal weakness & upper extremities
    • Variable in families: Some patients severely disabled, others mildly affected
    • Respiratory failure: Some patients
  • Dysphonia & Dysphagia: Early in disease course in some patients
  • Tendon reflexes: Absent
  • Pes cavus
  • Tremor (30%)
• Seum CK: Normal, or mildly elevated
• EMG: Mixed features
  • Myogenic: Proximal muscles
  • Neurogenic: Distal muscles
• NCV: Normal
• Muscle pathology¹⁴
  • Necrosis
  • Focal phagocytosis of muscle fibers
  • Rimmed vacuoles
    • Mainly in hypertrophic muscle fibers
    • Located near fiber surface
    • Lysosomal features
      • Acid phosphatase positive
      • LAMP-1 & LAMP-2 negative
      • LIMP-I on surface of vacuoles & fibers
    • Proteasome: Staining for ubiquitin & proteasome (19S & 20S) complex
    • Sarcolemmal proteins present
    • Contain basophilic granular debris
    • No amyloid or filaments

Hereditary Inclusion Body Myopathy (IBM1): Dominant

• Clinical
  • Onset: Adult; 25 to 40 years
  • Weakness
    • Quadriceps early
    • Distal: Foot Dorsiflexion
    • Proximal: After disease progression
  • CNS involvement: Some families
  • Progression: Slow
• Laboratory
  • Serum CK: Normal or Mildly increased
  • Pathology
    • Red rimmed vacuoles: Prominent on GT stain
    • Multifocal myopathic changes
      • Myopathic fascicles: Variation in fiber size; Endomysial fibrosis
      • Vacuoles more common in myopathic fascicles
    • ± Inflammation
• Also see: Other IBM
  • Inclusion body myositis: Sporadic; Proximal & Distal weakness
  • IBM2: Sporadic or Recessive; GNE; Chromosome 9p12; Distal weakness
  • IBM3: Joint contractures & ophthalmoplegia: Myosin heavy chain IIa; Chromosome 17p13; Dominant; Proximal weakness
  • IBM + Paget's & Dementia: Chromosome 9p13; Dominant; Proximal & Distal weakness
  • Differential diagnosis of rimmed vacuoles

Distal Myopathy with Vocal Cord & Pharyngeal Weakness (MPD2)

• Genetics
  • Similar locus to LGMD 1A: Myotilin mutations not present
• Onset
  • Age: 35 to 57 years; Average 46 years
  • Weakness: Legs (Anterior & Distal), Hands or Voice
• Clinical
  • Weakness
    • Initially asymmetric; May become symmetric
    • Legs: Peroneal distribution; May also involve inversion; Gastrocnemius relatively spared
    • Hands: Variable weakness in different finger extensors; Early in abductor policis brevis
    • Proximal: Shoulder weakness; Asymmetric; Especially deltoid
  • Voice
    • Onset usually after limb weakness
    • Initially: Hypophonic & breathy
    • Later: Wet, gurgling, hoarse with hypernasal resonance
  • Pharyngeal: Dysphagia & Aspiration
• Laboratory
  • Serum CK: Normal to 8x Normal
  • EMG: Myopathic (especially pharynx & vocal cords) or neuropathic changes
  • Nerve conductions: Normal or Mildly slowed
  • Muscle pathology
    • Myopathic: Gastrocnemius > Quadriceps
    • Internal nuclei
    • Rimmed vacuoles: Subsarcolemmal; Often elongated

Inclusion Body Myopathy with Dementia & Paget disease of Bone (IBMPFD)²

• Genetics¹²
  • Mutations: Missense
  • Locations
    • N-terminal: Exons 1 to 6
    • R95G; R155C; R155H; R155P; R159H; R191Q; A232E
  • Clinical genetic correlations
    • A232E: Fractures & Paget disease at earlier age
    • R159H: No dementia, Milder disease¹⁶
    • R155C: Frontotemporal dementia with intraneuronal inclusions
• VCP protein
  • Locations: Ubiquitous
  • Functions: Cell cycle & Membrane fusion
  • Binds ubiquitin
  • AAA ATPase
  • Mutated protein¹⁸
    • Causes increased levels of ubiquitinated cell proteins
    • Impairs degradation of proteins by endoplasmic reticulum-associated degradation (ERAD)
    • Promotes formation of aggregates: Contain p97/ VCP, ubiquitin conjugates & ER-resident proteins
    • Normal: Polymerization into hexamers; ATPase activity
• Epidemiology
  • > 10 US families
  • Male = Female
• Clinical
  • Onset
    • 3rd & 4th decade
    • Back pain

      IBM + Paget's: Scapular winging

  • Weakness (90%)
    • Marked variability in severity & pattern within families
    • Onset: Mean 43 years; Range 3 to 66 years
    • Legs: Distal & Proximal
    • Arms: Proximal & Distal
    • Other regions: Some patients
      • Scapular winging
      • Cranial nerves: Face; Tongue
      • Posterior neck: Head ptosis
    • Asymmetric: Often
    • Progression
      • Slow: Over decades
      • To severe disability
        • Severe weakness
        • Respiratory failure
      • Death in 40's to 60's
  • Bone disease

    IBM + Paget's: Paget's disease of bone

    • Paget disease (43%)
      • Spine: Most common lesion location
      • Other lesion locations: Hip, Skull; Pelvis
      • External link: Paget disease
    • Pain
    • Onset: Mean 42 years; Range 29 to 61 years
  • Dementia (37%)
    • Onset
      • Mean 54 years; Range 39 to 62 years
      • Usually after Paget's or Myopathy
    • Frontotemporal
      • Language: Anomia; Aphasia; Mutism
      • Personality change: Apathy; Agitation
      • Hallucinations: Visual; Auditory
      • Relatively preserved memory
  • Cardiomyopathy: Heart failure late in disease course
• Laboratory
  • Serum CK: Normal (80%), or Mildly increased (< 1165)
  • Serum Alkaline phosphatase: High with Paget disease
  • EMG
    • Spontaneous activity: Fibrillations; Positive sharp waves
    • Myopathy: Small amplitude, Polyphasic Brief motor unit potentials
  • NCV: Normal
  • Muscle biopsy
    • Atrophy: Regional
    • Hypertrophy: Scattered muscle fibers
    • Increased Endomysial connective tissue: Patchy
    • Rimmed vacuoles
    • VCP staining inclusions
  • Echocardiogram: Cardiomyopathy (Late)
  • Radiology: Paget disease of bone
  • Brain pathology: Cortical atrophy

Myopathy with Paget disease of Bone, type 2⁸

• Epidemilogy: 1 US family
• Onset: 4th & 5th decade
• Clinical
  • Weakness (50%)
    • Legs: Distal, Ankles & Toes
    • Upper extremity: Proximal; Scapular winging
  • Paget disease of bone (100%)
    • May be severe & widespread
    • Location: Long bones
• Laboratory
  • EMG: Myopathic
  • Muscle biopsy: Chronic active myopathy
    • Varied muscle fiber size
    • Increased endomysial connective tissue
    • Occasional muscle fiber degeneration & Regeneration
  • Serum CK: High or Normal; May become normal with progressive disease
  • Serum Alkaline phosphatase: High
  • Serum Osteocalcin: High in some patients

Distal Myopathy with early Respiratory failure (HIBM-ERF; ADMERF) ⁵

• Onset
  • 32 to 75 years
  • Younger in 2nd generation
  • Weakness: Symmetric; Foot dorsiflexion
• Clinical
  • Weakness
    • Distal legs: Anterior tibial
    • Progression: Proximal legs; Shoulders; ? Quadriceps sparing
    • Arms: Minimal weakness in most
    • Symmetric in most
    • Progression
      • Slow
      • Cane & occasionally wheelchair needed after 5 to 15 years
      • More rapid in 2nd generation patients
  • Respiratory failure: FVC < 75% of predicted in most patients at presentation
  • No contractures
• Laboratory
  • Serum CK: Normal to mildly elevated
  • EMG: Myopathic; Irritative
  • Nerve conduction studies: Normal
  • MRI of muscles
    • Proximal legs: Selective early involvement of semitendinosus & obturator externus
    • Distal legs: Most involvement of tibialis anterior; Relative sparing of gastrocnemius & soleus
    • Shoulder girdle: Moderate involvement of supraspinatus, infraspinatus, serratus anterior, subscapularis & trapezius
• Muscle pathology
  • Varied fiber size
  • Eosinophilic inclusions: Congophilic; Variably contain β amyloid, desmin, Phosphorylated tau
  • Muscle fiber splitting: With more severe weakness
  • Rimmed vacuoles: With more severe weakness
  • No necrosis or inflammation
  • No cytoplasmic bodies
  • Ultrastructure: Z-line streaming

Myopathy with ringed muscle fibers¹

• Inheritance: Sporadic
• Clinical features
  • Onset: 3rd decade
  • Weakness: Proximal (quadriceps) + Ankle dorsiflexion
  • Progression: Moderate 1 to 5 years
• Lab
  • Serum CK: Normal
  • EMG: Irritable myopathy
• Muscle Pathology
  • Myopathic: Fiber size variation; Increased connective tissue; Central nuclei
  • Rings in fibers: Outer sarcoplasmic pad; Middle annular myofibrils; Center normal

Distal Myopathy: MPD3 ⁹

• Genetics: Two possible loci 8p22-q11 & 12q13-q22
• Epidemiology: Single Finnish family
• Onset
  • Age: 32 to 45 years
  • Clumsiness of hands or legs
• Weakness
  • Legs
    • Distal
    • Anterior & Posterior
    • Muscles involved: TA, EDL, Gastrocnemius, Gluteus medius; TFL
  • Arms: Hands
    • Distal
    • Abductor pollicis; Opponens policis; 1st Dorsal interossei; Abductor digiti minimi
  • Asymmetric
  • Intrafamilial variability
  • Course: Progressive
    • Over years
    • To more proximal limbs: Forearm, Triceps, Infraspinatus, Proximal legs
    • Patients remain ambulatory
• Laboratory
  • EMG: Myopathic
  • Serum CK: Normal or Slightly elevated
• Muscle biopsy
  • Myopathy: Severe; Endomysial fibrosis; Fiber size variation
  • Rimmed vacuoles
  • Cytoplasmic inclusion bodies

Distal myopathy with spared anterior leg muscles¹⁵

• Epidemiology: Australian family
• Onset
  • Age: 0 to 30 years
  • Weakness
  • Muscle discomfort
• Clinical
  • Variable within family: Some affected members are asymptomatic
  • Weakness
    • Symmetric
    • Distal
    • Arms + Legs
      • Arms: Forearm pronators, Finger flexors, Intrinsic hand muscles
      • Legs: Ankle evertors, Plantar-flexors (Calf atrophy)
        • Differential diagnosis: LGMD 2B
    • Sparing: Anterior leg; Posterior arm
  • Muscle wasting: Distal
  • Discomfort
    • Type: Cramps; Deep pain
    • Worse after exercise
  • Tendon reflexes: Absent at ankles
  • Systemic: No cardiac or respiratory involvement
  • Course
    • Slowly progressive
    • Patients remain ambulatory
• Laboratory
  • Serum CK: Normal or Mildly elevated
  • EMG: Myopathic
  • MRI
    • Involvement of posterior & lateral leg muscles
    • Some asymmetry
  • Muscle
    • Varied fiber size: Small angular fibers
    • No vacuoles or inflammation
    • Dysferlin normal

Distal nebulin myopathy²⁰

• Genetics
  • Mutations: Missense
  • Different from Rod myopathy in which at least 1 mutation causes protein termination
  • Allelic with: Rod myopathy
• Clinical
  • Weakness
    • Distal
    • Hanging big toe sign
    • Extensor finger weakness: Index finger spared
  • Slender stature
• Muscle
  • Ultrastructure: Z-line streaming; Minor rod changes

Syndromes with Neuropathy & Myopathy

• Paraneoplastic (with weight loss > 15%)
  • Neuropathy: Distal; Sensory > Motor
  • Myopathy: Proximal with type II muscle fiber atrophy
• Inclusion Body Myositis
• Systemic disorders
  • Uremia
  • Acromegaly
  • Collagen vascular disorders
  • Sarcoid
  • HIV Infection
    • Myopathy: Inflammatory;
    • Several types of neuropathy
• Hereditary
  • Debrancher deficiency
  • Lamin A/C mutations
  • Congenital muscular dystrophy: Merosin deficiency
  • Marinesco-Sjögren
  • Mitochondrial: MNGIE Syndrome
  • Tyrosinemia
• Drugs & Toxins
  • Amiodarone
  • Chloroquine
  • Chlorphenoxy
  • Clofibrate: Risk factor - renal failure
  • Colchicine: Risk factor - renal failure
  • Doxorubicin
  • Eosinophilia-myalgia syndrome
  • Ethanol: Risk factor - fasting
  • Hydroxychloroquine
  • Organophosphates
  • Perhexiline
  • Vincristine