NM disorders

Question 1

Giant axonal neuropathy

Answer 1

• autosomal recessive; mutation in GAN gene (gigaxonin)
• sensorimotor neuropathy, corticospinal tract involvement with UMN signs, and optic atrophy –> vision loss
• characteristic gait: walk on inner edges of feet
• tightly curled hair
• large focal axonal swelling

Question 2

Refsum disease

Answer 2

• autosomal dominant peroxisomal dx
• accumulation of phytanic acid
• retinitis pigmentosa (night blindness and visual field constriction), cardiomyopathy, large fiber sensorimotor neuropathy, and skin changes

Question 3

Abetalipoproteinemia

Answer 3

• autosomal recessive disorder due to defect in triglyceride transport
• abnormal very low density lipoprotein –> fat malabsoprtion –> low levels A,E,D,K vitamin
• acanthocytes on peripheral smear
• retinitis pigmentosa, neuropathy, and ataxia

Question 4

Kearns-Sayre Syndrome

Answer 4

• mitochondrial disorder due to mutation in DNA

- retinitis pigmentosa, progressive opthalmoplegia, cardiac conduction defects, ataxia, myopathy, and hearing loss

Question 5

CMT1A

Answer 5

• Most common type of CMT
• demyelinating form
• slowly progressive weakness, muscle atrophy, kyphosis, hammertoes, high-arched feet, palpably enlarged nerves due to peripheral nerve hypertrophy, pes cavus
• due to mutation in peripheral myelin protein 22 (PMP22) on Chromosome 17
• pathology with onion bulb formation (also occur in CIDP)

Question 6

CMTX

Answer 6

• second most common type of CMT
• also demyelinating subtype
• x-linked inheritance –> males tend to be more affected
• mutation in connexin 32 gene

Question 7

CMT2

Answer 7

• accounts for 1/3 of autosomal dominant inherited neuropathies
• axonal subtype –> normal conduction velocities
• symptoms appear later and foot/spine deformities less severe
• multiple subtypes; genes affected are involved in axonal transport membrane trafficking

Question 8

HNPP

Answer 8

• autosomal dominant, incomplete penetrance
• caused by deletion in PMP22 (CMT1A caused by duplication of this gene)
• recurrent episodes of focal mononeuropathies
• peroneal nerve MC; then ulnar
• bx: focal, sausage like areas of thickening in myelin called tomacula

Question 9

Tangier’s disease

Answer 9

• autosomal recessive symmetric sensory neuropathy
• due to mutation in ABCA1 gene –> low cholesterol and high TG levels
• orange tonsils due to TG deposition; fat-laden MQ

Question 10

Multifocal Motor Neuropathy

Answer 10

• purely demyelinating motor neuropathy
• presents with asymmetric weakness due to involvement of peripheral nerves and no sensory sx
• may see anti-GM1 antibodies, but not required for diagnosis and not predictive of response to therapy
• EMG: may see conduction block + demyelinating fx. Sensory NCS are normal
• Tx: IVIG, rituximab, cyclophosphamide; do NOT respond to steroids or plasmapharesis