Clinical Guidance

X-linked adrenoleukodystrophy (X-ALD) affects the nervous system and the adrenal cortex. The involvement of nervous system and adrenal gland is independent and determines whether the affected male is diagnosed with cerebral disease, adrenomyeloneuropathy, or primary adrenocortical insufficiency. The range of phenotypic expression in X-ALD is wide and cannot be predicted by very long-chain fatty acid (VLCFA) levels, the ABCD1 pathogenic variant, or family history. Varying phenotypes often co-occur in a single kindred or sibship. Some individuals with X-ALD remain asymptomatic until their adult years.

Diagnostic Criteria

Note: For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care .

Suggestive Findings

The three scenarios in which X-linked adrenoleukodystrophy (X-ALD) may be considered are a , a , and a male who is asymptomatic but .

Scenario 1: Positive Newborn Screening Result

Newborn screening (NBS) for X-ALD has been added to the recommended uniform screening panel in the United States and, to date, more than half the states have begun screening. While the specific methodologies vary, testing is presently performed measuring the concentration of C26:0-lysophosphatidylcholine (C26:0-LPC) .

Management Guidelines

With the institution of newborn screening and increasing numbers of individuals being diagnosed with X-linked adrenoleukodystrophy (X-ALD), clinical practice guidelines have been developed for diagnosis and treatment; see (full text), (full text), and (full text). Evaluations Following Initial Diagnosis Confirmed Positive Newborn Screening Result: Initial Evaluations For male infants with a positive newborn screening (NBS) result for X-ALD, the initial evaluations summarized in are recommended in order to prevent life-threatening complications of primary adrenal insufficiency and to develop a plan for neurologic and brain MRI monitoring to identify promptly those at risk for childhood cerebral adrenoleukodystrophy (cCALD). Boys identified with early changes on brain MRI consistent with cCALD are candidates for targeted therapy to prevent progression of central nervous system disease. Table 4. Recommended Evaluations and Next Steps for Infants with a Confirmed Positive Newborn Screening Result for X-Linked Adrenoleukodystrophy

Surveillance Guidelines

Childhood Cerebral Adrenoleukodystrophy (cCALD)

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended for males with cCALD.

Table 11.

Recommended Surveillance for Males with Childhood Cerebral Adrenoleukodystrophy (cCALD)

System/Concern | Evaluation | Frequency