Table 1.

Clinical features of adrenoleukodystrophy.

	Pre-symptomatic Screening	Presentation	Treatments
Adrenal insufficiency	• ACTH and cortisol • At diagnosis of ALD • <2 years: 3–4 months • ≥2 years: 4–6 months • PRA and electrolytes • After diagnosis of glucocorticoid deficiency, every 6 months	• Subclinical abnormalities of glucocorticoid secretion as early as 5 weeks of life • Peak incidence between 3–10 years • Approximately half of patients do not develop mineralocorticoid deficiency • Lifetime prevalence >80%	• Chronic glucocorticoid replacement therapy • Chronic mineralocorticoid replacement, if needed • Stress-dose steroids for acute physiologic stress • No current curative therapy
Myelopathy	• Annual clinical neurologic assessment	• Onset between 20–40 years (median of 28 years) • Peripheral neuropathy is often the first manifestation • Primary manifestation is spinal cord dysfunction • 27–63% develop cerebral involvement, 10–20% associated with rapid neurologic decline • Detected by spinal cord atrophy on T2-weighted MRI	• Supportive care • Does not appear to be impacted by a history of HSCT for cerebral ALD • No curative therapy
Cerebral ALD	• Brain MRI • 12–36 months, annually • 3–10 years, every 6 months • 10–18 years, annually	• Onset between 4–12 years, with peak age at 7 years • Affects one-third of boys with ALD • First manifestation is asymptomatic lesions on brain MRI followed by learning and behavioral problems • If untreated, universally progressive with rapid neurological decline and total disability by 6 months to 2 years, and death within 5–10 years after diagnosis	• HSCTPros: • Arrests progression of neurologic disease in early stage • Improved survival outcomes (5-year, 95% transplanted vs. 54% untransplanted) Cons: • Not effective in advanced cerebral ALD • Requires matched stem cell donor • Risk of acute mortality, failure of engraftment, and GVHD • Gene therapy (in clinical trials)Pros: • Arrests progression of neurologic disease • Brain MRI and neurological outcomes in the short term are comparable to HSCT • No risk of GVHD Cons: • Risk of failure of engraftment • Theoretical risk of insertional oncogenesis • Unknown long-term outcomes
Women with ALD	• None	• Onset typically 30 years and later • Myelopathy similar to men • Neuropathic pain (generally not present in males) in 20% who are younger than 40 years and 90% older than 60 years • Conventional imaging does not show abnormalities, but spinal cord volume not yet assessed • Milder and slower progression compared to men	• Supportive care • No approved treatments

Abbreviations: ALD, adrenoleukodystrophy; PRA, plasma renin activity; HSCT, hematopoietic stem-cell transplant.