Unresponsive 4-Year-Old Boy Found to Have X-Linked Adrenoleukodystrophy

A 4-year-old boy presented with right gaze deviation, diminished tone, right hand shaking, and unresponsiveness for 30 minutes. Language comprehension was regressing over the past 2 years and over the past month there had been intermittent esotropia, unsteady gait, and stuttering speech. Head computed tomography was notable for bilateral white matter lesions with calcifications ([Fig. 1]). Brain magnetic resonance imaging revealed symmetric fluid-attenuated inversion recovery hyperintensity of the posterior bilateral white matter with restricted diffusion ([Fig. 2]). The findings were specific for X-linked adrenoleukodystrophy (ALD).[1] C26 very long chain fatty acid (VLCFA) was elevated, as were the C24/C22 and C26/C22 ratios. Adrenocorticotropic hormone was elevated diagnosing concomitant adrenal insufficiency.

Fig. 1 Computed tomography scan with bilateral posterior white matter changes and associated calcifications.

Fig. 2 Sagittal fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging with posterior hyperintensity (above). Axial FLAIR view with butterfly distribution of posterior symmetric hyperintensities (below). Findings suggestive of adrenoleukodystrophy.

ALD results from deficient VLCFA β-oxidative degradation due to impaired peroxisomal transport resulting in accumulation.[1] [2] Classically, this disease is marked by progressive neurobehavioral decline in addition to adrenal insufficiency.[3] Acute presentations occur 9.3% of the time with status epilepticus and encephalopathy accounting for 0.8 and 1% of total cases, respectively.[3] Bone marrow transplant (BMT) is a mainstay therapy for this disorder and can prevent and possibly reverse demyelination if begun early in the disease course. Without BMT, patients progress to a vegetative state or death.[4]

• References

• 1 Engelen M, Kemp S, de Visser M. , et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis 2012; 7 (01) 51
• 2 Vawter-Lee MM, Hallinan BE, Burrow TA, Spaeth CG, Arthur TM. A novel catastrophic presentation of X-linked adrenoleukodystrophy. JIMD Rep 2015; 24: 97-102
• 3 Stephenson DJ, Bezman L, Raymond GV. Acute presentation of childhood adrenoleukodystrophy. Neuropediatrics 2000; 31 (06) 293-297
• 4 Shapiro E, Krivit W, Lockman L. , et al. Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet 2000; 356 (9231): 713-718