What is the treatment for Adrenoleukodystrophy (ALD)?

Treatment of Adrenoleukodystrophy (ALD)

Immediate Diagnostic and Therapeutic Priorities

Males with suspected ALD must be screened by measuring very long-chain fatty acids (VLCFAs) in serum, and those with confirmed adrenal insufficiency require lifelong glucocorticoid and mineralocorticoid replacement therapy. 1

Adrenal Insufficiency Management

• All ALD patients with primary adrenal insufficiency should receive 15-25 mg of hydrocortisone daily (or 18.75-31.25 mg cortisone acetate) in split doses, with the first dose immediately after waking and the last dose at least 6 hours before bedtime 1
• Children require 6-10 mg/m² body surface area of hydrocortisone 1
• Mineralocorticoid replacement with fludrocortisone 50-200 µg daily as a single dose is essential, with children and younger adults often requiring higher doses 1
• Patients should be advised to take salt and salty foods ad libitum 1

Disease-Modifying Interventions

Hematopoietic stem cell transplantation (bone marrow transplantation) is currently recommended for patients with early cerebral involvement who have a well-matched donor available. 2 This represents the only intervention that can halt progression in the cerebral form when initiated early.

Dietary Therapy: Lorenzo's Oil

Lorenzo's oil (4:1 mixture of glyceroltrioleate and glyceroltrierucate) should NOT be routinely prescribed to patients with ALD who already have neurological deficits, as it neither improves neurological function nor arrests disease progression despite normalizing plasma VLCFA levels. 3

Evidence Against Lorenzo's Oil in Symptomatic Patients

• In a study of 22 patients treated for a median of 2.5 years, plasma C26:0 normalized in 86% of patients, yet disability still increased in those with neurological symptoms 3
• Cerebral demyelination developed in previously asymptomatic patients despite treatment 3
• Significant adverse effects occur frequently: liver enzyme elevations (55%), thrombocytopenia (55%), gastrointestinal complaints (14%), and gingivitis (14%) 3

Potential Role in Asymptomatic Patients

• Preliminary data suggest dietary therapy with Lorenzo's oil combined with VLCFA restriction, when begun in neurologically asymptomatic patients, may reduce the frequency and severity of later neurological disability 4, 2
• This approach is advisable for asymptomatic patients at present, though confirmation is still needed 2

Emerging and Investigational Therapies

Gene therapy and allogeneic stem cell transplantation represent the most promising disease-modifying treatments for ALD, particularly when implemented before significant neurological deterioration occurs. 5

• A trial utilizing beta interferon and thalidomide has been conducted, though results are not yet definitive 2
• VLCFA normalization strategies remain investigational 5

Critical Monitoring and Follow-Up

• Patients require annual review at minimum, including assessment of health and well-being, weight, blood pressure, and serum electrolytes 1
• Monitor for development of new autoimmune disorders, particularly hypothyroidism 1
• Bone mineral density should be assessed every 3-5 years to monitor for complications of glucocorticoid therapy 1
• Neuroimaging should be performed for any new headache or neurologic signs to assess for cerebral abscess, hemorrhage, or stroke 1

Common Pitfalls to Avoid

• Never delay hydrocortisone administration in suspected adrenal crisis while waiting for diagnostic procedures; treat immediately with 100 mg IV or IM hydrocortisone followed by 100 mg every 6-8 hours until recovered 1
• Do not assume Lorenzo's oil will prevent progression in symptomatic patients—the evidence clearly shows it does not 3
• Recognize that ALD has extreme phenotypic heterogeneity even within the same family, suggesting influence of modifier genes 2
• All patients should wear a Medic Alert Bracelet and carry a steroid card to inform medical personnel of their chronic adrenal insufficiency status 1

Newborn Screening Advocacy

Newborn screening for ALD enables early detection and intervention before irreversible neurological damage occurs, though it remains unavailable in many regions including India. 5 Early detection allows for:

• Timely initiation of adrenal hormone therapy when needed 5
• Consideration of stem cell transplantation before cerebral involvement progresses 5
• Genetic counseling and carrier identification for family planning 6