This patient has progressive ataxia, dysmetria, and dysarthria.  With a family history of similar symptoms, the most likely diagnosis is Friedreich ataxia (FA), the most common hereditary form of ataxia.  This degenerative condition is due to an autosomal recessive mutation in the frataxin gene, which leads to degeneration of the posterior columns and spinocerebellar tracts; affected patients usually have symptom onset in adolescence and a shortened life span.

A condition that can mimic FA is vitamin E deficiency.  Vitamin E is a lipid-soluble, antioxidant vitamin that is widely available in the diet; deficiency is rare and typically occurs in patients with fat malabsorption (eg, cystic fibrosis) or abetalipoproteinemia.  Neurologic dysfunction in vitamin E deficiency occurs due to free radical damage to neuronal cell membranes.  Shared features of FA and vitamin E deficiency include:

• Ataxia due to degeneration of spinocerebellar tracts

• Loss of position and vibration sense due to degeneration of the dorsal columns

• Weakness and loss of deep tendon reflexes due to peripheral nerve degeneration

Patients with suspected FA but without a frataxin mutation should undergo vitamin E testing.  Unlike FA, individuals with vitamin E deficiency often have additional hemolytic anemia due to free radical damage of erythrocyte membranes.  Vitamin B₁₂ deficiency may also present similarly to FA due to subacute combined degeneration of the dorsal and lateral spinal columns.

(Choice A)  Acute intermittent porphyria presents with acute attacks of abdominal pain and peripheral neuropathy (eg, numbness, paresthesias), not progressive ataxia.  In addition, it does not cause spinal cord degeneration.

(Choice B)  Guillain-Barré syndrome typically presents after a diarrheal (eg, Campylobacter jejuni) or upper respiratory infection with symmetric, ascending weakness, hyporeflexia, and paresthesias due to demyelination of peripheral nerves.  The spinal cord is not affected, so proprioception remains intact and ataxia does not occur.

(Choice C)  Lead intoxication is usually asymptomatic but can cause nonspecific gastrointestinal symptoms (eg, constipation, abdominal pain) and neurobehavioral problems (eg, poor memory, difficulty concentrating).  Severe toxicity may lead to encephalopathy and ataxia, but spinal cord degeneration would not be seen.

(Choice D)  Creutzfeldt-Jakob disease is a prion disease that presents with progressive dementia and myoclonic jerks of the extremities.  Ataxia can occur due to involvement of the cerebellum.  However, patients usually experience rapid neurologic decline and death within a year of symptom onset.

Educational objective:
Neurologic symptoms of vitamin E deficiency closely mimic those of Friedreich ataxia and include ataxia (spinocerebellar tract degeneration), loss of position and vibration sense (dorsal columns degeneration), and weakness and hyporeflexia (peripheral nerve degeneration).