A mind unravelling: a case report of adult adrenoleukodystrophy

Background

X-linked adrenoleukodystrophy (ALD) is a rare X-linked peroxisomal disorder caused by pathogenic variants in the ABCD1 gene, particularly affecting the adrenal cortex, spinal cord, and cerebral white matter.[1,2] While adrenal insufficiency is often the earliest manifestation—sometimes preceding neurological symptoms by years—progressive demyelination of the central nervous system typically leads to spastic paraparesis, ataxia, cognitive decline, and ultimately severe disability if untreated.[3] Psychiatric manifestations may represent the initial or predominant presentation in adult-onset cases, delaying diagnosis.[4] Early recognition of ALD has implications for neurological monitoring, genetic counseling, endocrine management, and consideration of disease-modifying interventions in selected cases.[5] We describe a case of adult-onset X-ALD presenting initially with isolated obsessive sexual thoughts.

Case Presentation

A 27-year-old single male with no previous psychiatric history reports a one-month history of intrusive, ego-dystonic obsessive sexual thoughts. The patient refers Addison’s disease diagnosed at age five, for which he has been receiving regular treatment. He denies compulsive behavior, hallucinations, delusions, cognitive complaints, but admits to reduced need for sleep, increased goal-directed activity, hypersexual behavior, irritability, and episodic disorganized conduct described as fugue-like states. Insight is preserved, and neurological examination is unremarkable.

A diagnosis of obsessive-compulsive disorder is considered, and treatment with SSRIs is initiated (fluvoxamine). At one month follow-up, the patient reports little to no improvement, he additionally complains of sexual dysfunction, including reduced libido and erectile difficulties. Interpreted as a medication side effect, he is switched to a different SSRI; however symptoms remain unchanged.

The clinical picture evolves with persistent low mood, self-reproach, social withdrawal, and suicidal ideation without actual attempts. Multiple pharmacologic adjustments are tried, including escitalopram, sertraline, venlafaxine, valproate, aripiprazole, haloperidol, mirtazapine, with only partial or transient improvement.

Around the five month follow up, the patient complains gait disequilibrium and unsteadiness. New neuroimaging is pursued. Brain CT scan comes out as inconclusive. Brain MRI is executed as the next step, showing bilateral symmetric white matter hyperintensities involving the pontine–mesencephalic internal capsules, indicative for adrenoleukodystrophy. Subsequent genetic testing is ordered and a pathogenic mutation in the ABCD1 geneis confirmed, establishing a diagnosis of X-linked adrenoleukodystrophy.

The patient is referred to endocrinology and neurology services for multidisciplinary management and further evaluation for disease-modifying therapy.

Discussion

Our case portrays a presentation of adult-onset X-linked adrenoleukodystrophy presenting as a psychiatric disorder. Obsessive sexual thoughts with no prior psychiatric history, unresponsiveness to treatment, and absence of typical OCD progression represented early red flags for further organic examination. Psychiatric symptoms are well-documented early manifestations of adult cerebral adrenoleukodystrophy and may precede neurological deficits by months to years. Often coexisting, endocrine abnormalities, especially adrenal dysfunction, may provide important diagnostic clues. In our case, the emergence of gait disequilibrium and characteristic MRI findings allowed diagnostic clarification. The take home message remains the necessity of clinicians maintaining a high index of suspicion for underlying organic etiologies in patients presenting with atypical or treatment-resistant symptoms, especially when systemic comorbidities are present. Early identification has significant implications for prognosis, therapeutic planning and long-term monitoring.

References

1. Kemp S, Berger J, Aubourg P. X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta. 2012;1822(9):1465–1474.
2. Bezman L, et al. Incidence of X-linked adrenoleukodystrophy and the relative frequency of its phenotypes. Am J Med Genet. 2001;100(2): 130–134.
3. Moser HW, et al. X-linked adrenoleukodystrophy. Nat Clin Pract Neurol. 2007;3(3):140–151.
4. Powers JM, et al. Adreno-leukodystrophy: a review of neuropathologic features and pathogenesis. Acta Neuropathol. 2000;100: 487–501.
5. Mallack EJ, et al. Newborn screening for X-linked adrenoleukodystrophy: review of outcomes and management. Int J Neonatal Screen. 2020;6(4):87.