History and Physical
A 10-year-old boy with a history of second-degree consanguinity started experiencing learning difficulties 6 months before consultation. The problem was attributed to attention deficit without hyperactivity disorder and was addressed by educators and school guidelines. One year later, he started to fall to the ground with amnesia after episodes. Physical examination was normal. A vitamin deficiency was suspected, and he was treated with methylphenidate and vitamin therapy (B 6 ) for 6 months.
Basic plasma analysis and EEG were requested, which were normal. However, his symptoms did not improve, and he was referred to child neurology. The neurological examination revealed spasticity with hyperreflexia, positive Babinski, bradypsychia, and brown staining of the skin, conjunctivae, and gums.
Diagnostic Workup
Hormonal analysis was requested with a thyroid study and basal cortisol and long-chain fatty acids, confirming a decrease in basal cortisol.
Brain MRI showed diffuse white matter T2 hyperintensity and T1 hypointensity, predominantly posteriorly. Confluent, symmetrical areas of T2 hyperintensity were predominantly in the splenium of the corpus callosum. Over time, these extended into the parieto-occipital periventricular white matter ( Fig. 28.1 ) with volume loss and secondary atrophy of the corpus callosum and thalami ( Fig. 28.2 ).
Boy with X-linked adrenoleukodystrophy. Brain MRI, (A) sagittal T1, (B and C) axial T2, (D) coronal FLAIR, (E) axial T1 with contrast, (F) coronal T1 with contrast show signal abnormality of the splenium of corpus callosum, right corticospinal tract, and posterior periventricular white matter with leading-edge enhancement.
Boy with X-linked adrenoleukodystrophy. Brain MRI, (A) sagittal T1, (B) axial T2, (C) coronal FLAIR, (D) axial T1 show abnormal signal and atrophy in the splenium of corpus callosum and posterior periventricular white matter.
Laboratory testing for very long-chain fatty acids and sensory evoked potentials was immediately requested.
Clinical Differential Diagnosis
The initial presentation of pediatric neurodegenerative disorders can be mistaken for attention deficit disorder, learning disorder, or other behavioral disturbance. Visual, hearing, and motor problems can be very subtle in the early stages of the disease. Cognitive deficits become evident as the disease progresses. In 90% of untreated patients, there is a loss of all neurological functions (motor, cognitive, language, and behavioral) over a time range of 6 months to 3 years.
Many patients can manifest symptoms of adrenocortical insufficiency at the onset of symptoms, which should alert the physician to order laboratory testing and make a differential diagnosis.
Of course, we also have to consider other differential diagnoses with childhood-adolescent-onset neurodegenerative diseases such as metachromatic leukodystrophy (MLD), juvenile Krabbe disease, and other lysosomal storage diseases.
Imaging Differential Diagnosis
Peroxisomal acyl-CoA oxidase deficiency: Much rarer with some similar MRI features. The typical findings are progressive white matter abnormalities, atrophy, and contrast enhancement in the centrum semiovale. Polymicrogyria has sometimes been described.
Metachromatic leukodystrophy: Characteristic imaging features include deep white matter involvement with perivenular sparing and late involvement of subcortical U fibers, accompanied by global atrophy over time.
Krabbe disease ( Fig. 28.3 ): As with many leukodystrophies, Krabbe disease shows distinct imaging features and ages of onset for different clinical subtypes. The subtypes that can resemble X-linked adrenoleukodystrophy (ALD) are the juvenile and adult forms, with deep white matter and/or isolated corticospinal tract involvement.
