X-Linked Adrenoleukodystrophy: Included Clinical Scenarios and Key Management Issues

Clinical ScenarioKey Management Issues
Scenario 1: Positive newborn screening (NBS) resultMale infants w/positive NBS for X-ALD & confirmed ABCD1 pathogenic variantRefer all male infants to:
  • A pediatric endocrinologist for screening for primary adrenocortical insufficiency to prevent life-threatening complications of adrenal insufficiency;
  • A neurologist or biochemical geneticist to develop a plan to monitor neurologic & brain MRI findings to identify promptly those at risk for cCALD &, thus, candidates for targeted therapy to prevent progression of CNS disease.
Female infants w/positive NBS for X-ALDRefer parents for genetic counseling to identify male relatives at risk for X-ALD & primary adrenocortical insufficiency who might warrant diagnostic evaluation & management as recommended for male infants w/positive NBS. 1
Scenario 2: Symptomatic individualChildhood CALD 2, 3
  • Adrenal assessment;
  • Consultation w/center w/expertise in evaluating males for possible HSCT
Adrenomyeloneuropathy
  • Measure cortisol & ACTH levels to evaluate for concomitant adrenal insufficiency.
  • Brain MRI to evaluate for cerebral disease 1
Primary adrenocortical insufficiency (Addison disease)Provide appropriate steroid replacement & consult w/endocrinologist.
Scenario 3:
Male identified by family screening		May be asymptomatic or symptomaticAssess clinically w/appropriate endocrine studies & brain MRI.

ACTH = adrenocorticotropic hormone; CALD = cerebral adrenoleukodystrophy; CNS = central nervous system; HSCT = hematopoietic stem cell transplantation; X-ALD = X-linked adrenoleukodystrophy

For synonyms and outdated names see Nomenclature.

1.
2.

Childhood CALD (cCALD) is also referred to as cerebral adrenoleukodystrophy (CALD), but cerebral disease is not exclusive to children.

3.

Confirmed in males with elevated very long-chain fatty acids (VLCFAs) and identification of a hemizygous pathogenic variant in ABCD1, and in females by elevated VLCFAs or C26:0-lysophosphatidylcholine and identification of a heterozygous ABCD1 pathogenic variant in ABCD1.

From: X-Linked Adrenoleukodystrophy

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