Other Rare Disorders

Friedreich’s Ataxia (FA)

• AR hereditary spinocerebellar degenerative disease

• GAA trinucleotide repeat expansion in the FXN gene on chromosome 9.

• deficiency of frataxin (iron-sulfur cluster formation in mitochondria) → mitochondrial Fe2+ accumulation → oxidative stress → neuronal degeneration.

• Affects primarily:
• Dorsal columns (loss of proprioception and vibration)
• Spinocerebellar tracts (ataxia)
• Lateral corticospinal tracts (spastic weakness)
• Dorsal root ganglia (sensory neuron loss)

• Also causes systemic effects: hypertrophic cardiomyopathy, diabetes mellitus, and skeletal deformities (pes cavus, scoliosis).

• Onset typically in childhood or adolescence.

• Gait ataxia (first symptom) → progresses to limb incoordination and frequent falls.

• Dysarthria, dysmetria, and intention tremor due to cerebellar involvement.

• Sensory loss (vibration and proprioception).

• Weakness and spasticity from corticospinal tract degeneration.

• Non-neurologic findings:
• Cardiomyopathy (leading cause of death)
• Diabetes mellitus
• Skeletal deformities (scoliosis, pes cavus).

• Gait: wide-based, unsteady, with positive Romberg sign.

• Reflexes: absent lower limb reflexes despite upgoing Babinski signs.

• Coordination: dysmetria, intention tremor, impaired heel-to-shin testing.

• Speech: scanning or slurred dysarthria.

• Other: evidence of scoliosis or high-arched feet; cardiac exam may reveal murmurs of hypertrophic cardiomyopathy.

• No cure; management is supportive and multidisciplinary.

• Friedreich’s ataxia causes a progressive spinocerebellar and corticospinal degeneration presenting as ataxia with sensory and pyramidal signs.

• Neurosurgical relevance: patients may present for scoliosis correction or cardiac evaluation prior to anesthesia—anticipate restrictive lung disease and cardiomyopathy perioperatively.

Subacute combined degeneration

• Vitamin B12 (cobalamin) deficiency → demyelination of:
• Dorsal (posterior) columns → loss of vibration and proprioception
• Lateral corticospinal tracts → spasticity and weakness

• Mechanism: impaired methylmalonyl-CoA → succinyl-CoA conversion → accumulation of methylmalonic acid → abnormal myelin and axonal degeneration

• Common causes: Pernicious anemia (loss of intrinsic factor), Malabsorption (gastric bypass, Crohn’s, ileal resection), Strict vegan diet (no B12 intake), Nitrous oxide abuse (oxidizes and inactivates B12)

• Gradual, progressive course over weeks to months

• Sensory: paresthesias, numbness, loss of vibration and proprioception, sensory ataxia

• Motor: spasticity, weakness, hyperreflexia, positive Babinski signs

• Gait: ataxic–spastic gait due to combined posterior and lateral tract involvement

• Other: cognitive changes, depression, irritability, possible optic neuropathy

• Exam: positive Romberg sign, impaired position sense, mixed UMN and posterior column signs

• Positive Romberg sign (loss of proprioception)

• Mixed upper motor neuron and posterior column signs

• Hyperreflexia with extensor plantar responses

• Loss of vibration and position sense in feet and legs

• May show broad-based or spastic gait

• Vitamin B12 replacement:
• 1 mg IM daily × 1 week → weekly × 1 month → monthly for life if irreversible cause
• Oral B12 acceptable if absorption intact (dietary deficiency)

• Monitor: hemoglobin, reticulocyte count, and neurologic response

• Prognosis: hematologic recovery rapid; neuro recovery may be incomplete if tx delayed