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SENSORY DISORDERS: Small Fiber

Metabolic Diabetes mellitus Hypertriglyceridemia Hereditary Amyloidosis Hereditary Sensory Neuropathy I (HSAN I) Congenital sensory neuropathy with anhidrosis (HSN IV) Congential insensitivity to pain sensation without anhidrosis Hereditary ataxia with thermoanalgesia & loss of fungiform papillae An-α-lipoproteinemia (Tangier's) α-galactosidase (Fabry's) Hereditary sensory neuropathy + Spastic paraparesis (Cavanagh's variant) Hereditary sensory neuropathy with loss of pain perception Congenital indifference to pain Navajo neuropathy with arthropathy Cold-Induced Sweating Syndrome Toxic: Kepone; Ciguatera Infection: Leprosy M-protein Idiopathic: Often painful

Unmyelinated axons

• Genetics
  • 3 point mutations identified (C133Y, C133W, V144D)
  • Founder effect in Australian & English families
• Serine palmitoyltransferase (SPT) enzyme: Sphingolipid biosynthesis
  • Catalyzes pyridoxal-5'-phosphate-dependent condensation of L-serine & palmitoyl-CoA to 3-oxosphinganine
  • Mutation effects
    • Increased Glucosyl ceramide synthesis: ? Leads to apoptosis
    • Reduced serine palmitoyltransferase activity
    • Normal levels of protein
• Clinical features
  • Onset: 2nd decade or later; Average 25 years
  • Distribution: Distal > proximal; Symmetric; Legs > Arms sensory, autonomic & reflex loss
  • Sensory
    • Loss: Pain & Temperature (Small fiber); Large fiber loss also occurs
    • Spontaneous sensations: Paresthesias are Rare; Lancinating pains in some kindreds; Burning pain in some
  • Charcot's joints (Neurogenic osteoarthropathy)
    • Progression: Succession of exacerbations
    • Location: Feet, Severe mutilation & shortening; Occasional hands, Thickened fingers
    • X-rays: Distal demineralization; Metatarsal tapering (Licked candy-stick)
  • Weakness
    • Common late in course
    • Distal
  • Autonomic involvement
    • Rare
    • Occasional: Horner syndrome
  • Sensorineural deafness: Variably present
  • Skin: Blistering; Edema & discoloration of foot; Chronic ulcers; Painless injuries
  • Time course: Slow progression
• Laboratory
  • Electrophysiology: Loss of C > Aδ & Aα axons
  • Immune: Increased Synthesis of IgA
• Pathology
  • Loss of dorsal root ganglion cells & later motor neurons
  • Predominant loss of small myelinated & unmyelinated axons
  • No CNS changes
• See: Other Hereditary sensory neuropathies

• Onset: Congenital
• Clinical
  • Sensory loss
    • Pain
    • Temperature
    • Location: Extremities
  • Acromutilation
  • Normal: Large fiber sensation; Strength; Tendon reflexes
• Nerve pathology
  • Small myelinated A-delta fibers: Absent
  • Unmyelinated axons: Normal

• Genetic: Mutation
  • Missense: Arg211Trp
• NGF-b protein
  • Neurotrophin family
  • Functions: Role in development & maintenance of sympathetic & sensory nervous systems
  • Cellular location: Secreted
• Epidemiology: Northern Swedish family
• Clinical: Variable degrees of severity
  • Onset: Early childhood to adult
  • Sensory loss
    • Pain perception: Reduced
    • Temperature: Reduced
  • Skeletal: Charcot joints & Fractures
    • Onset: Childhood or Adult (3rd & 4th decade)
    • Lower extremities: Feet; Ankles; Knees
  • Autonomic
    • Sweating: Normal
    • Fainting: 1 patient
    • GU & GI disorders: 1 patient
• Laboratory
  • Electrophysiology
    • Nerve conduction velocity: Normal
    • Sensory loss: Temperature ± Vibration
    • R-R interval: Normal
  • Nerve pathology
    • Axon loss: Thinly myelinated & Unmyelinated
    • Less axon loss in adult onset cases

• Onset: 5th decade
• Neuropathy
  • Sensory: Impaired pain & temperature sensation
  • Motor: Unremarkable
  • Nerve pathology: Loss of myelinated > unmyelinated axons
• Ataxia
• Autonomic:
  • Fungiform papillae of tongue: Absent
  • Reduced lacrimation, taste, temperature control (fevers)
  • Constipation/diarrhea; Bladder dysfunction; Vasomotor instability
• Other: Emotional instability; Hearing loss