A Novel Catastrophic Presentation of X-Linked Adrenoleukodystrophy

Abstract

Objective: We report a novel presentation of childhood cerebral X-linked adrenoleukodystrophy: status epilepticus followed by abrupt and catastrophic neurologic deterioration.

Methods: A description of the clinical presentation, laboratory evaluation, and imaging findings leading to a diagnosis of X-linked adrenoleukodystrophy.

Results: A 3-year-old male with prior history of autism presented with fever, diarrhea, and status epilepticus requiring a pentobarbital coma. Admission labs were notable only for a glucose level of 22 mg/dL, which stabilized after correction. The child never returned to his prior neurologic baseline, with complete loss of gross motor, fine motor, and speech skills. Serial brain magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) was notable for progressive diffuse cortical signal changes with swelling, diffusion restriction, and ultimately laminar necrosis. Nine months after presentation, CSF (cerebrospinal fluid) protein and MRS lactate were persistently elevated, concerning for a neurodegenerative disorder. This led to testing for mitochondrial disease, followed by lysosomal and peroxisomal disorders. Very long-chain fatty acids were elevated. Identification of a pathogenic ABCD1 mutation confirmed the diagnosis of X-linked adrenoleukodystrophy.

Conclusions: Boys with childhood cerebral X-linked adrenoleukodystrophy typically present with gradual behavioral changes. Rare reports of boys presenting with transient altered mental status or status epilepticus describe a recovery to their pre-presentation baseline. To our knowledge this is the first X-ALD patient to present with status epilepticus with abrupt and catastrophic loss of neurologic function. X-linked adrenoleukodystrophy should be suspected in young males presenting with seizures, acute decline in neurologic function, with persistently elevated CSF protein and MRS lactate.

Competing interests: None declared

Appendices

Synopsis

Practitioners should consider the diagnosis of X-linked adrenoleukodystrophy in males presenting with status epilepticus followed by neurologic deterioration, especially if the patient has elevated CSF protein, MRI white matter changes, or a lactate peak on MRS.

Compliance with Ethics Guidelines

Conflict of Interest

Marissa Vawter-Lee, Barbara Hallinan, T. Andrew Burrow, Christine Spaeth, and Todd Arthur declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the guardian of the patient included in this study. Proof that informed consent has been obtained is available upon request.

Author Contributorship Statement

Marissa M Vawter-Lee: conception and design, data acquisition, analysis, interpretation of data, writing of the manuscript, final approval of article

Barbara E Hallinan: conception and design, interpretation of data, writing of the manuscript, final approval of article

T. Andrew Burrows: interpretation of data and writing of the manuscript

Christine G Spaeth: interpretation of data and writing of the manuscript

Todd M Arthur: conception and design, interpretation of data, writing of the manuscript, final approval of article