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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
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Spectrum of clinical disease in X-linked adrenoleukodystrophy (X-ALD)

Spectrum of clinical disease in X-linked adrenoleukodystrophy (X-ALD)
Phenotype Age at presentation Symptoms and signs Diagnostic tests Follow-up tests Usual therapy
Males
Childhood cerebral ALD
Asymptomatic with normal MRI Variable; most commonly <4 years
  • None
  • Usually comes to light through newborn screening or testing family member of a patient with X-ALD
  • Confirm with DNA testing
  • Adrenal function tests
  • Monitor MRI
  • Family screening
  • Glucocorticoid replacement therapy, if indicated
Asymptomatic with abnormal MRI 2 to ≥10 years
  • None
  • VLCFA levels
  • Brain MRI
  • Confirm diagnosis with DNA testing
  • Adrenal function tests
  • Neurologic and neuropsychological testing
  • Family screening
  • HCT
  • Gene therapy is an experimental alternative treatment
  • Glucocorticoid replacement therapy, if indicated
Early cerebral ALD 3 to 10 years; rarely presents at age >15 years
  • Behavior changes
  • School difficulties
  • Cognitive deficits
  • Audiovisual changes
  • VLCFA levels
  • Brain MRI
  • Confirm diagnosis with DNA testing
  • Adrenal function tests
  • Neurologic and neuropsychological testing
  • Family screening
  • HCT
  • Gene therapy is an experimental alternative treatment
  • Glucocorticoid replacement therapy, if indicated
Spontaneously arrested ALD 3 years to adulthood
  • None or stable symptoms as with early cerebral ALD
  • VLCFA levels
  • Brain MRI
  • Confirm diagnosis with DNA testing
  • Adrenal function tests
  • Neurologic and neuropsychological testing
  • Family screening
  • Glucocorticoid replacement therapy, if indicated
  • Important not to pursue HCT or GT
Advanced cerebral ALD 5 years to adulthood
  • Dementia
  • Psychoses
  • Paralysis
  • Epilepsy
  • Loss of vision
  • Loss of speech
  • Bulbar palsy
  • VLCFA levels
  • Brain MRI
  • Confirm diagnosis with DNA testing
  • Adrenal function tests
  • Neurologic and neuropsychologic testing
  • Family screening
  • Glucocorticoid replacement therapy, if indicated
  • Supportive care
Pure cerebral ALD in adulthood
Cerebral ALD without preceding AMN Adolescence to adulthood
  • Similar symptoms as in childhood cerebral ALD
  • VLCFA levels
  • Brain MRI
  • Confirm diagnosis with DNA testing
  • Adrenal function tests
  • Neurologic and neuropsychological testing
  • Family screening
  • Glucocorticoid replacement therapy, if indicated
  • Supportive care
  • Possibly HCT*
Adrenomyeloneuropathy (AMN)
Pure AMN 20 to 40 years
  • Paraparesis
  • Sphincter disturbances
  • Sensory changes
  • Incoordination
  • Erectile dysfunction
  • Numbness and pain from polyneuropathy
  • VLCFA levels
  • Confirm with DNA testing
  • Adrenal function tests
  • Brain MRI
  • MTS
  • SSEP
  • Family screening
  • Glucocorticoid replacement therapy, if indicated
  • Physical therapy
AMN with cerebral involvement 20 to 40 years
  • Like pure AMN plus:
    • Dementia
    • Behavioral disturbances
    • Psychosis
    • Epilepsy
    • Aphasia
    • Visual loss
    • Bulbar palsy
  • VLCFA levels
  • Brain MRI
  • Confirm with DNA testing
  • As in pure AMN plus:
    • Neurologic and neuropsychological testing
    • EEG
    • Psychiatry evaluation
  • Glucocorticoid replacement therapy, if indicated
  • Physical therapy for AMN symptoms
  • Supportive care
  • Possibly HCT*
Cerebellar
Olivo-ponto-cerebellar Childhood; adolescence
  • Ataxia
  • Brainstem signs
  • VLCFA levels
  • Brain MRI
  • Confirm with DNA testing
  • Adrenal function tests
  • Neurologic testing
  • Family screening
  • Glucocorticoid replacement therapy, if indicated
  • Physical therapy
Adrenal insufficiency only
Adrenal insufficiency with normal MRI 0 to ≥10 years
  • Primary adrenocortical insufficiency
  • Adrenal function tests
  • VLCFA levels
  • Confirm with DNA testing
  • Monitor MRI
  • Neurologic and neuropsychological testing
  • Family screening
  • Glucocorticoid replacement therapy
Adrenal insufficiency with abnormal MRI 0 to ≥10 years
  • Primary adrenocortical insufficiency
  • Adrenal function tests
  • VLCFA levels
  • Brain MRI
  • Confirm with DNA testing
  • Neurologic and neuropsychological testing
  • Family screening
  • HCT
  • Glucocorticoid replacement therapy
Female carriers
Asymptomatic Younger women tend to be asymptomatic
  • None
  • DNA testing is required for diagnosis
  • False negatives can occur with VLCFA testing
  • Neurologic examination
  • Adrenal function tests
  • Monitor MRI
  • Family screening
  • Genetic counseling
  • General support
Symptomatic Rare in women <30 years old; frequency rises sharply with age
  • Paraparesis
  • Sphincter disturbances
  • Numbness and pain from polyneuropathy
  • Incoordination
  • Fatigue
  • DNA testing is required for diagnosis
  • False negatives can occur with VLCFA testing
  • Adrenal function tests
  • MTS
  • SSEP
  • Family screening
  • Genetic counseling
  • Physical therapy
  • Supportive care
  • Glucocorticoid replacement therapy, if indicated (adrenal insufficiency is rare)
Percentages listed above vary by age group. The asymptomatic and adrenal insufficiency only groups decline with age while the ALD and AMN groups increase.
ALD: adrenoleukodystrophy; MRI: magnetic resonance imaging; VLCFA: very long chain fatty acids assay in plasma; AMN: adrenomyeloneuropathy; ADHD: attention deficit hyperactivity disorder; HCT: hematopoietic stem cell transplant; ALS: amyotrophic lateral sclerosis; N/A: not applicable; MTS: magnetization transfer MRI cervical cord; SSEP: somatosensory evoked potential; EEG: electroencephalogram.
* HCT may be an option for some adult patients with AMN who have mild cerebral involvement. Refer to UpToDate topic on adrenoleukodystrophy for additional details.
¶ The frequency of symptoms rises from <20% in women under 40 years of age, to almost 90% in women older than 60 years.
Adapted from: Moser HW, Raymond GV, Dubey P. Adrenoleukodystrophy: New approaches to a neurodegenerative disease. JAMA 2005; 294:3131.
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