An 11-year-old girl is brought to the office due to an unsteady gait. Her parents first noticed increasing clumsiness 6 weeks ago, which has since progressed to difficulty standing and walking. The patient has had no recent illnesses, including fever, cough, or diarrhea. She takes no medication and has no allergies. She has scoliosis for which she sees an orthopedic surgeon twice a year. The patient was adopted, and the only known family history is sudden cardiac death in her biological father. Her adoptive mother has anxiety that is well controlled with medication. On examination, the patient is found to have a wide-based gait and constantly shifts her position to maintain balance. The lower extremities have decreased vibratory and position sense, and ankle jerks are absent bilaterally. Which of the following is the most likely diagnosis in this patient?
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This patient's history and physical examination findings are most consistent with Friedreich ataxia (FA), an autosomal recessive condition characterized by an excessive number of trinucleotide repeat sequences (most commonly GAA), resulting in an abnormality of the frataxin protein. Frataxin is highly expressed in the brain, heart, and pancreas. Therefore, the typical clinical presentation of FA includes:
Neurologic dysfunction
Cardiomyopathy
Diabetes mellitus
Neurologic findings of FA include dysarthria, loss of deep tendon reflexes, and progressive gait and limb ataxia in adolescence. Loss of position and vibratory senses also occurs due to deterioration of the dorsal spinal column. Hypertrophic cardiomyopathy occurs in most patients, with increased risk of arrhythmia and heart failure, and patients may have a family history of sudden cardiac death. Skeletal comorbidities of FA include kyphoscoliosis and pes cavus (high-arched feet).
The diagnosis of FA can be confirmed with genetic testing. Mean age of death is 30-40 due to complications of cardiomyopathy. Management involves a multidisciplinary approach (including physical therapy and psychological support), as no disease-modifying therapies are currently available.
(Choice A) Acute cerebellar ataxia typically occurs following an infection (eg, varicella infection), and presents with acute onset (within hours or days) of ataxia, nystagmus, and dysarthria. Vibratory and position senses and reflexes are not affected, and symptoms usually resolve within 2 weeks.
(Choice B) Benzodiazepines are sedative-hypnotic medications that, in excess, can cause ataxia, dysarthria, and depressed mental status. The prolonged time course and loss of vibratory and position sense in this patient are inconsistent with benzodiazepine toxicity.
(Choice D) Guillain-Barré syndrome is an immunologic polyneuropathy that classically presents with ascending weakness and areflexia that worsens over hours to days. Ataxia and position sense loss are not features of Guillain-Barré syndrome.
(Choice E) Although lead toxicity can cause peripheral neuropathy, it also characteristically presents with neurobehavioral changes (eg, irritability, hyperactivity), fatigue, and abdominal pain. Children with oral mouthing behaviors (eg, infants) are at higher risk, and ataxia is not a typical feature of lead toxicity.
Educational objective:
Friedreich ataxia is an autosomal recessive, neurodegenerative disease that typically presents in adolescence with progressive ataxia, dysarthria, scoliosis, and cardiomyopathy. Loss of vibratory sense and proprioception also occur due to degeneration of the dorsal spinal columns.